Cumulative Incidence Of All-cause Death Research Articles

Abstract PO5-18-02: A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality

Abstract Background Most patients with high-risk non-metastatic breast cancer are treated with neoadjuvant chemotherapy (NAC), which includes the administration of anthracyclines. The omission of anthracyclines was shown to be associated with excellent outcomes in selected patients. However, the extent to which anthracyclines are omitted among a population of women treated with NAC and its impact on mortality remain unclear. Objective To investigate the extent to which anthracyclines are omitted among a population of patients with invasive breast cancer treated with NAC and to examine the impact of non-anthracycline NAC on risks of breast cancer-specific and all-cause mortality. Methods We performed a retrospective population-based cohort analysis using patient-level health administrative data. The cohort includes women aged ≥18 years with stage I – III invasive breast cancer diagnosed between January 2012 and December 2020, treated with NAC and surgery. Patients were excluded if they received < 50% of the planned chemotherapy regimen, had bilateral breast cancer and/or a previous malignancy. The exposure of interest was anthracycline versus non-anthracycline NAC regimen. The primary and secondary endpoints were breast cancer-specific mortality and overall (all-cause) mortality. Multivariable Cox proportional hazards models adjusted by propensity score, and clinical/pathologic variables including a measure of comorbidity was performed to examine impact of omission of anthracyclines on outcomes. Cumulative incidence curves were generated to calculate the 5-year cumulative incidence of breast cancer and all-cause mortality for the whole cohort and in subset analyses, stratified by stage and receptor subtype. Results The cohort includes 4,180 women. Median follow was 62 months (IQR 44-85) and median age was 51 years (IQR 43-60). Most patients had low co-morbidities (96.0%), Stage II (44.1%) or Stage III (47.7%) disease, underwent mastectomy (72.6%), had axillary node dissection (64.4%) and received post-operative radiotherapy (88.8%). 279 (6.7%) individuals were treated with a non-anthracycline NAC and 3,901 (93.3 %) received an anthracycline NAC. Women who received non-anthracycline NAC were older (median 62 years vs. 50 years; p< 0.001), more likely to have stage I-II disease (77.0% vs. 51.3%; p< 0.001), and more likely to have triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p< 0.001) than those who received anthracyclines.On propensity adjusted multivariable analysis, factors associated with an increased risk of BC mortality include Stage III (HR 9.3, 95%CI 4.5 - 19.2, p< 0.0001) or stage II at presentation (HR 2.57 95% CI 1.24, 5.34, p=.01) (ref: stage I) or triple negative subtype (HR 3.7 95% CI 3.03, 4.51, p< .0001) (ref: hormone positive/HER2-). There was no significant difference in the relative risks of BC death (HR 0.8, 95% CI 0.5-1.27) or all-cause mortality (HR 0.85, 95% CI 0.60-1.21) for patients selected for treatment without anthracyclines compared to those treated with anthracyclines.Overall, among individuals selected for treatment without or with anthracycline NAC there was no significant difference in the 5-year cumulative incidence of BC (15.4% vs 10.5%, P=.05) or all-cause mortality (16.4% vs 11.9%, P=.07). However, the 5-year cumulative incidence of BC specific death (31.8% vs 16.5%, p=.03) and 5-year cumulative incidence of all-cause death (31.8% vs. 18.2%, p=.06) was higher among 420 women with HER2+ Stage III breast cancer who received non-anthracycline versus anthracycline-based chemotherapy. No difference was observed for other subgroups. Conclusions The omission of anthracyclines in NAC for individuals with stage III HER2+ breast cancer was associated with higher cumulative risks of breast cancer and all-cause mortality but no difference was observed for other subgroups. Further research is warranted to better understand in whom anthracyclines can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Rinku Sutradhar, Matthew Castelo, Lena Nguyen, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-02.

Two-year outcomes of drug-coated balloon only strategy for de novo lesions in large coronary vessels

Abstract Background Drug-coated balloons (DCB) are effective for the treatment of in-stent restenosis and de novo lesions in small coronary vessels (reference vessel diameter: RVD < 3.0 mm). Recently, several studies have reported acceptable results of DCB for de novo lesions in large coronary vessels (RVD ≧ 3.0 mm). However, previous studies were limited, we investigated the clinical outcomes of the DCB only strategy for de novo lesions in large coronary vessels. Methods We retrospectively analyzed 97 patients with 107 de novo lesions (RVD ≧ 3.0 mm) who underwent DCB only angioplasty from January 2016 to December 2021. We scheduled angiographic follow-up at 6 months after procedure and analyzed quantitative coronary angiography (QCA) data. Results The mean duration of follow-up was 737.8 ± 512.6 days. Patients who met the high bleeding risk (HBR) criteria was 56 (57.7%). Procedure success rate was 97.2% (3 lesions needed bailout drug eluting stent implantation) and acute coronary occlusion was not observed. The 2-year cumulative incidences of all-cause death was 7.1%, cardiac death was 1.6%. Target vessel revascularization was 9.2%, target lesion revascularization was 4.2%, respectively. Two patients had major bleeding events (BARC type 3 or 5) within 3 months after treatment and during the DAPT period. No major bleeding events were observed during the SAPT period. Conclusion The clinical outcomes of the DCB only strategy for de novo lesions in large coronary vessels were safe and acceptable. Especially in HBR patients, DCB only strategy could be an alternative treatment option.

The incidence and risk factors of newly-diagnosed cancer after diagnosis of venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background/Introduction Venous thromboembolism (VTE) may be the earliest sign of cancer, although there are no established screening strategies for occult cancer. This could be partly due to lack of the real-world incidence and risk factors of occult cancer after diagnosis of VTE in the current era. Purpose The current study aimed to evaluate clinical characteristics and outcomes between patients who were newly diagnosed with cancer after diagnosis of VTE and those who were not, and investigate incidence and risk factors of newly-diagnosed cancer after diagnosis of VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population was consisted of 3706 patients without known active cancer at diagnosis of VTE, who were divided into patients with newly-diagnosed cancer after diagnosis of VTE (N=250, 6.7%) and those without (N=3456, 93.3%). To explore risk factors of newly-diagnosed cancer, we constructed the multivariable Cox proportional hazard model which consisted of variables with P values <0.05 in univariate analysis. Results The cumulative incidences of newly-diagnosed cancer were 1.5% at 30-day, 3.7% at 1-year, 7.0% at 3-year, 11.1% at 5-year, and 16.0% at 7-year. The most common types of newly-diagnosed cancer was colon (17.2%), followed by lung (14.8%) and blood (8.0%). Patients with newly-diagnosed cancer were older (71.6 vs. 67.2 years, P<0.001) and had lower body mass index (22.9 vs. 23.8 kg/m2, P=0.004) than those without. Patients with newly-diagnosed cancer more frequently had several comorbidities such as history of cancer (35% vs. 11%, P<0.001), hypertension (51% vs. 44%, P=0.04), diabetes mellitus (21% vs. 16%, P=0.03), and autoimmune disorder (20% vs. 13%, P=0.004), whereas they less frequently had transient provoking risk factors for VTE (29% vs. 39%, P<0.001). The cumulative incidence of all-cause death was significantly higher in patients with newly-diagnosed cancer than those without (59.3% vs. 21.0% at 7-year). The multivariable Cox proportional hazard model revealed that old age (hazard ratio [HR]: 1.02 per 1 year [1.01-1.03], P<0.001), history of cancer (HR: 3.60 [2.75-4.67], P<0.001), autoimmune disorder (HR: 1.51 [1.09-2.05], P=0.01), and absence of transient provoking risk factors for VTE (HR: 1.36 [1.03-1.80], P=0.03) were independently associated with newly-diagnosed cancer after diagnosis of VTE. Conclusions In the current era, the incidence of newly-diagnosed cancer was 3.7% at 1-year with initial acute increase followed by continuous increase, and several independent risk factors were identified, which might be useful for consideration of optimal screening strategies for occult cancer based on individual risk.Newly-diagnosed cancer

Abstract 15165: Clinical Characteristics and Outcome of Venous Thromboembolism in Patients After Surgical Procedure: From the COMMAND VTE Registry-2

Background: Undergoing surgical procedure is a risk factor for venous thromboembolism (VTE). However, the prognosis of VTE in patients after surgical procedure has not been fully evaluated in the Era of direct oral anticoagulant (DOAC). We elucidated the prognosis of VTE in patients who have undergone surgical procedure. Methods: The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. According to the history of surgical procedure within 2 months, we divided the study patients into 2 groups; Surgical group (N=793) and Non-surgical group (N=4404). Clinical outcome including all-cause death and recurrence of VTE was compared between the two groups. Results: There were more women in surgical group than non-surgical group (64% vs. 58%, P<0.01). In addition, surgical group had higher prevalence of active cancer (34% vs. 28%, P<0.01), and lower prevalence of kidney disease (16% vs. 20%, P<0.01) than non-surgical group. The cumulative incidences of all-cause death and recurrent VTE at 2-year were significantly lower in surgical group than non-surgical group (all-cause death: 16.6±1.4% vs. 24.4±0.7%, P<0.01; recurrent VTE: 2.8±0.7% vs. 5.7±0.4%, P<0.01, respectively). In surgical group, Cox regression analysis identified diabetes mellitus as the independent risk factor for recurrence of VTE (hazard ratio 2.90; 95% confidence interval, 1.24-6.74; P=0.01). Conclusion: Patients after surgical procedure had lower mortality and incidence of recurrent VTE than non-surgical group. Diabetes mellitus is the independent risk factor for recurrence of VTE in patients after surgical procedure.

Asymptomatic vs. symptomatic atrial fibrillation: Clinical outcomes in heart failure patients

BackgroundThe outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified. MethodsIn a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF. ResultsA total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %).After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both). ConclusionsIn a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %.

Mid-term outcomes and hemodynamic performance of transcatheter aortic valve implantation in bicuspid aortic valve stenosis: Insights from the bicuSpid TAvi duraBILITY (STABILITY) registry.

Limited data are available on transcatheter heart valves (THVs) durability in bicuspid aortic valve (BAV) stenosis. To evaluate evaluating 4-year clinical and echocardiographic outcomes of patients with BAV undergoing transcatheter aortic valve implantation (TAVI). The bicuSpid TAvi duraBILITY (STABILITY) registry is an Italian multicentre registry including all consecutive patients with BAV and severe aortic stenosis (AS), treated by means of TAVI between January 2011 and December 2017. Outcomes of interest were all-cause death at 4-year, over time changes in echocardiographic measurements, and THV durability according to the valve aortic research consortium (VARC)-3 update definitions. Study population included 109 patients (50% females; mean age 78 ± 7.5 years) with a mean Society of Thoracic Surgeons Predicted Risk of Mortality score of 5.1 ± 4.3%. Median follow-up (FU) duration was 4.1 years [interquartile range: 2.8-5.1]. The overall cumulative incidence of all-cause death by Kaplan-Meier estimates at 4 years was 32%. Compared to baseline, a significant decrease in transprosthetic mean gradient was obtained after TAVI (54 ± 16 vs. 10 ± 5 mmHg; p < 0.001), whereas a significant increase was observed at 4-year (13 ± 6.4 mmHg, p = 0.03). Cumulative incidence of hemodynamic valve dysfunction (HVD) was 4%. Six patients met HVD criteria: three moderate and three severe HVD. All three cases of severe HVD were clinically relevant (bioprosthetic valve failure[BVF]) with two patients receiving a reintervention (TAVI in TAVI), and one patient experiencing a valve-related death due to endocarditis. The STABILITY registry suggests that in patients with severe AS and BAV undergoing TAVI, postprocedural clinical benefits might last, over time, up to 4-year FU. The low rates of severe HVD and BVF may support the hypothesis of good THV durability also in BAV recipient.

Association of Metformin Treatment with Risk for Death in Diabetic Patients with Concomitant Gastric Cancer.

Despite the existing guideline's recommendation of metformin therapy as the initial approach for managing diabetes mellitus (DM), there remains a scarcity of comprehensive documentation regarding metformin's impact on outcomes that are important for patients. The objective of this study was to assess the potential impact of metformin treatment on the risk of death in individuals diagnosed with both gastric cancer and pre-existing diabetes mellitus (DM); Design, Setting, and Participants: The study made use of a dataset encompassing nationwide health insurance claims, allowing for a retrospective analysis of all patients with a history of gastric cancer diagnosis (classified under International Classification of Diseases 10th Revision code: C16.X) spanning from 1 January 2002 to 31 December 2012. The primary objective was to observe death within a 5-year follow-up period. The study population comprised 63,664 individuals who fell into two categories: those treated with metformin (n = 29,548) and those who did not receive metformin treatment (n = 34,116). This classification was based on the initial treatment allocation following the diagnosis of gastric cancer. Metformin treatment, comorbidities, concurrent medication, and procedural information. All-cause death, disease-specific death, cardiovascular death. During the 5-year follow-up period, the metformin treatment group exhibited a lower cumulative incidence of all-cause death (27.5%) in comparison to the group not receiving metformin treatment (32.8%). Furthermore, the relative hazards for all-cause death were significantly reduced in the metformin treatment group (HR: 0.80, 95% CI 0.78-0.82), indicating a lower risk of death when compared to the non-metformin group. In addition, metformin treatment was associated with lower occurrences of disease-specific death (related to gastric cancer) and cardiovascular death when compared to the group not undergoing metformin treatment. The findings demonstrated that the use of metformin was effective at improving prognosis among gastric cancer patients documented with prior DM. In this population-based cohort study, metformin treatment was associated with reduced risk of mortality.

The predictive value of relative wall thickness on the prognosis of the patients with ST-segment elevation myocardial infarction

ObjectiveThe study aimed to evaluate the prognostic value of relative wall thickness (RWT) in the patients with ST-segment elevation myocardial infarction (STEMI).MethodsA total of 866 patients with STEMI admitted in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from November 2010 to December 2018 were enrolled in the current study retrospectively. Three methods were used to calculate RWT: RWTPW, RWTIVS+PW and RWTIVS. The included patients were divided according to the median values of RWTPW, RWTIVS+PW, and RWTIVS, respectively. Survival analysis were performed with Kaplan–Meier plot and multivariate Cox proportional hazard model was established to evaluate the adjusted hazard ratio of the three kinds of RWT for all cause death, cardiac death and MACE (major adverse cardiac death).ResultsThere was no significance for the survival analysis between the low and high groups of RWTPW, RWTIVS+PW and RWTIVS at 30 days and 12 months. Nonetheless, the cumulative incidence of all cause death and cardiac death in the low group of RWTPW and RWTIVS+PW was higher than those in the high group at 60 months. The cumulative incidence of MACE in the low group of RWTPW was higher than the high group at 60 months. Multivariate Cox regression model showed that RWTPW were inversely associated with long-term cardiac death and MACE in STEMI patients. In the subgroup analysis, three calculations of RWT had no predictive value for the patients with anterior myocardial infarction. By contrast, RWTPW was the most stable independent predictor for the long-term outcomes of the patients with non-anterior myocardial infarction.ConclusionRWTPW, RWTIVS+PW and RWTIVS had no predictive value for the long-term clinical outcomes of patients with anterior myocardial infarction, whereas RWTPW was a reliable predictor for all cause death, cardiac death and MACE in patients with non-anterior myocardial infarction.

Association of dynamic change of triglyceride-glucose index during hospital stay with all-cause mortality in critically ill patients: a retrospective cohort study from MIMIC IV2.0

BackgroundBiomarker of insulin resistance, namely triglyceride-glucose index, is potentially useful in identifying critically ill patients at high risk of hospital death. However, the TyG index might have variations over time during ICU stay. Hence, the purpose of the current research was to verify the associations between the dynamic change of the TyG index during the hospital stay and all-cause mortality.MethodsThe present retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV) critical care dataset, which included data from 8835 patients with 13,674 TyG measurements. The primary endpoint was 1-year all-cause mortality. Secondary outcomes included in-hospital all-cause mortality, the need for mechanical ventilation during hospitalization, length of stay in the hospital. Cumulative curves were calculated using the Kaplan–Meier method. Propensity score matching was performed to reduce any potential baseline bias. Restricted cubic spline analysis was also employed to assess any potential non-linear associations. Cox proportional hazards analyses were performed to examine the association between the dynamic change of TyG index and mortality.ResultsThe follow-up period identified a total of 3010 all-cause deaths (35.87%), of which 2477 (29.52%) occurred within the first year. The cumulative incidence of all-cause death increased with a higher quartile of the TyGVR, while there were no differences in the TyG index. Restricted cubic spline analysis revealed a nearly linear association between TyGVR and the risk of in-hospital all-cause mortality (P for non-linear = 0.449, P for overall = 0.004) as well as 1-year all-cause mortality (P for non-linear = 0.909, P for overall = 0.019). The area under the curve of all-cause mortality by various conventional severity of illness scores significantly improved with the addition of the TyG index and TyGVR. The results were basically consistent in subgroup analysis.ConclusionsDynamic change of TyG during hospital stay is associated with in-hospital and 1-year all-cause mortality, and may be superior to the effect of baseline TyG index.

Effect of left ventricular ejection fraction Spectrum on 1-Year mortality in patients with acute ischemic stroke or transient ischemic attack.

We aimed to investigate the association of the left ventricular ejection fraction (LVEF) spectrum with 1-year clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). In a prospective registry for the Third China National Stroke Registry (CNSR-III), AIS or TIA patients with echocardiography records during hospitalization were recruited. All LVEFs were categorized into intervals of 5% in width. The lowest and highest intervals are ≤40% and >70%, respectively. The primary outcome was all-cause death at 1 year. Cox proportional hazards regression analysis was performed to investigate the association between baseline LVEF and clinical outcomes. This analysis included a total of 14,053 patients. In total, 418 patients died during 1-year follow-up. Overall, LVEF ≤60% was associated with a higher risk of all-cause death compared to LVEF >60%, independent of demographic and clinical characteristics (aHR 1.29 [95% CI 1.06-1.58]; p = 0.01). The cumulative incidence of all-cause death was significantly different among the eight LVEF groups that survival declined successively with the decrease of LVEF (log-rank p ≤ 0.0001). Patients with AIS or TIA with decreased LVEF (≤60%) had a lower 1-year survival rate after onset. LVEF 50%-60% even within the normal range, may still contribute to poor outcomes in AIS or TIA. Comprehensive evaluation of cardiac function after acute ischemic cerebrovascular disease should be strengthened.

Fifteen-year clinical prognosis and cardiovascular or limb event associated with homocysteine levels in peripheral arterial disease

BackgroundThere are limited reports on the relationship between plasma homocysteine (Hcy) levels and long-term all-cause death (ACD), cardiovascular events, or limb events in patients with peripheral arterial disease (PAD). We examined the relationship between plasma Hcy levels and 15-year these events in PAD patients. MethodsWe performed a prospective cohort study in 955 PAD patients. The patients were divided into four groups based on plasma Hcy levels with median (interquartile range). The endpoints were cumulative incidences of ACD, major adverse cardiovascular events (MACE), and MACE plus limb events (MACLE). ResultsThe incidences of ACD, MACE, and MACLE were correlated with plasma Hcy levels (P < 0.05). In multiple regression analysis, plasma Hcy had positive correlations with C-reactive protein (CRP), men, and critical limb ischemia (CLI) and negative correlations with estimated glomerular filtration rate (eGFR) and high-density lipoprotein cholesterol (p < 0.05). In Cox multivariate analysis, higher Hcy (HR 1.614, 95 % CI 1.229–2.119, p = 0.001), age, CRP, brain natriuretic peptide (BNP), D-dimer, lower body mass index, ankle brachial pressure index (ABI), serum albumin, eGFR, CLI, coronary heart disease (CHD), cerebrovascular disease, and diabetes were related to ACD; higher Hcy (HR 1.242, 95 % CI 1.004–1.535, p = 0.045), age, BNP, lower ABI, serum albumin, diabetes, and CHD were related to MACE; and higher Hcy (HR 1.290, 95 % CI 1.057–1.574, p = 0.012), BNP, lower ABI, serum albumin, CHD, and diabetes were related to MACLE (P < 0.05). Statins improved ACD, MACE, and MACLE (p < 0.01). ConclusionsPlasma Hcy was a risk factor for 15-year ACD, MACE, and MACLE in patients with PAD.

External Validation of the Japanese Clinical Score for Mortality Prediction in Patients With Acute Heart Failure.

To predict mortality in patients with acute heart failure (AHF), we created and validated an internal clinical risk score, the KICKOFF score, which takes physical and social aspects, in addition to clinical aspects, into account. In this study, we validated the prediction model externally in a different geographic area.Methods and Results: There were 2 prospective multicenter cohorts (1,117 patients in Osaka Prefecture [KICKOFF registry]; 737 patients in Kochi Prefecture [Kochi YOSACOI study]) that had complete datasets for calculation of the KICKOFF score, which was developed by machine learning incorporating physical and social factors. The outcome measure was all-cause death over a 2-year period. Patients were separated into 3 groups: low risk (scores 0-6), moderate risk (scores 7-11), and high risk (scores 12-19). Kaplan-Meier curves clearly showed the score's propensity to predict all-cause death, which rose independently in higher-risk groups (P<0.001) in both cohorts. After 2 years, the cumulative incidence of all-cause death was similar in the KICKOFF registry and Kochi YOSACOI study for the low-risk (4.4% vs. 5.3%, respectively), moderate-risk (25.3% vs. 22.3%, respectively), and high-risk (68.1% vs. 58.5%, respectively) groups. The unique prediction score may be used in different geographic areas in Japan. The score may help doctors estimate the risk of AHF mortality, and provide information for decisions regarding heart failure treatment.

Life Expectancy of Patients With Severe Aortic Stenosis in Relation to Age and Surgical Risk Score

BackgroundThere is a paucity of data regarding shorter life expectancy after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). MethodsAmong 3815 patients with severe AS enrolled in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry, there were 1469 patients (initial AVR: n = 647; conservative strategy: n = 822) with low surgical risk, 1642 patients (initial AVR: n = 433; conservative strategy: n = 1209) with intermediate surgical risk, and 704 patients (initial AVR: n = 117; conservative strategy: n = 587) with high surgical risk. Among 1163 patients who actually underwent surgical AVR as the initial strategy, patients were divided into 4 groups according to age <65 years (n = 185), 65 to 74 (n = 394), 75 to 80 (n = 345), and >80 (n = 239). The expected survival of the general Japanese population was obtained from the Statistics Bureau of Japan. The surgical risk was estimated using The Society of Thoracic Surgery (STS) score. ResultsThe median follow-up was 3.7 years. The cumulative incidences of all-cause death were significantly lower in the initial AVR strategy than in the initial conservative strategy across the 3 STS groups. Shorter life expectancy after surgical AVR was seen especially in younger patients. The observed mortality in low-risk patients was comparable to the expected mortality across all the age-groups, while intermediate-risk patients aged <75 years, and high-risk patients across all age-groups had higher mortality compared with the expected mortality. ConclusionsThe risk stratification according to age and STS score might be useful to estimate shorter life expectancy after AVR, and these findings have implications for decision making in the choice of surgical or transcatheter AVR.

298 MPACT OF GUIDELINES-ORIENTED AGE CUT-OFF IN INTERMEDIATE TO LOWVRISK PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT WITH NEWEST GENERATION SELF-EXPANDING VALVES: A COMBINED ANALYSIS FROM NEOPRO AND NEOPRO-2 REGISTRIES

Abstract Introduction While randomized controlled trials have widely shown superiority or non-inferiority of transcatheter aortic valve replacement (TAVR) across the whole spectrum of surgical risks, 2021 ESC guidelines on valvular heart disease provide a class Ia indication for TAVR for patients at high surgical risk or, alternatively, aging &amp;gt;=75 years, irrespective of their surgical risk. Conversely, for patients aging &amp;lt;75 y and at low risk, surgical aortic valve replacement is recommended. Thus, in intermediate-low (IL) risk patients, the 75 y age cut-off is pivotal to guide the choice of intervention. The aim of the present study was to explore the impact on such cut-off on clinical outcomes in a real-world setting. Methods Consecutive IL surgical risk patients enrolled in the NEOPRO and NEOPRO-2 registries were included. A 1:1 propensity score matching (PSM) was used to match patients aged &amp;gt;= vs. &amp;lt;75 years old. The primary endpoint was the composite of all-cause death or cardiovascular hospitalizations. Results A total of 3642 patients undergoing TAVR with self-expanding transcatheter heart valves (THVs) from 2012 to 2021 were enrolled. After PSM, 484 patients (N=242 in both groups) were included in the final analysis. Mean age was 70.1±5.2 in patients aged &amp;lt;75 y and 81.56±4.18 in those aged &amp;gt;=75 y (p&amp;lt;0.001), while mean Society of Thoracic Surgeon (STS) score was 3.6±2.5%. Implanted THVs were Acurate Neo, Evolut Pro, Acurate Neo 2 and Evolut Pro+ in 199 (41.1%), 188 (38.8%), 73 (15.1%) and 24 (5%) patients respectively, with no between-groups differences. Rates of in-hospital complications were comparable across the two age categories. At 1-year follow-up, the cumulative incidence of all-cause death was 11% in patients aged &amp;gt;=75 y and 13% in those aged &amp;lt;75y (Log-Rank p=0.627); similarly, the composite of all-cause death or cardiovascular hospitalizations occurred in 14% vs. 16% of patients (Log-Rank p=0.554). Conclusions TAVI has comparable benefit across age strata in IL risk patients. The age cut-off suggested by current guidelines is not predictive of adverse events during hospital stay, neither of all-cause mortality through a mid-term follow-up. This opens the question to future studies focusing on lifetime management and not age cut-off.

Sex difference after acute myocardial infarction patients with a history of current smoking and long-term clinical outcomes: Results of KAMIR Registry.

The contribution of sex as an independent risk factor for cardiovascular disease still remains controversial. The present study investigated the impact of sex on long-term clinical outcomes in Korean acute myocardial infarction (AMI) patients with a history of current smoking on admission after drug-eluting stents (DESs). A total of 12,565 AMI patients (male: n = 11,767 vs. female: n = 798) were enrolled. Major adverse cardiac events (MACEs) comprising all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcomes that were compared between the two groups. Probable or definite stent thrombosis (ST) was the secondary outcome. After adjustment, the early (30 days) cumulative incidences of MACEs (adjusted hazard ratio [aHR]: 1.457; 95% confidence interval [CI]: 1.021-2.216; p = 0.035) and all-cause death (aHR: 1.699; 95% CI: 1.074-2.687; p = 0.023) were significantly higher in the female group than in the male group. At 2 years, the cumulative incidences of all-cause death (aHR: 1.561; 95% CI: 1.103-2.210; p = 0.012) and Re-MI (aHR: 1.800; 95% CI: 1.089-2.974; p = 0.022) were significantly higher in the female group than in the male group. However, the cumulative incidences of ST were similar between the two groups (aHR: 1.207; 95% CI: 0.583-2.497; p = 0.613). The female group showed worse short-term and long-term clinical outcomes compared with the male group comprised of Korean AMI patients with a history of current smoking after successful DES implantation. However, further studies are required to confirm these results.

Patterns and trends in the cause of death for patients with endometrial cancer.

Racial disparities in endometrial cancer have been reported in the United States, but trends and the underlying causes are not well understood. We aimed to examine the trends and contributing factors in racial disparities for causes of death among endometrial cancer patients. In this population-based cohort study, we identified 139 473 women diagnosed with first, primary endometrial cancer between 1992 to 2018 from the Surveillance, Epidemiology, and End Results Program. We used the "Fine and Gray" method to calculate the cumulative incidence of all-cause and specific-cause death. We used proportional subdistribution hazard (PSH) and cause-specific hazard (CSH) models to quantify the relative risk of Black-White disparities. We performed a mediation analysis to assess the contribution of potential factors to disparities. The cumulative incidence of all-cause death decreased in endometrial cancer patients, with estimates at 5 years of 26.72% in 1992-1996 and 22.59% in 2007-2011. Compared with White patients, Black patients persistently had an increased risk of death due to endometrial cancer (PSH hazard ratio [HR] = 2.05, 95% confidence interval [CI] = 1.90 to 2.22; CSH HR = 2.19, 95% CI = 2.00 to 2.40) and causes other than endometrial cancer (PSH HR = 1.23, 95% CI = 1.10 to 1.37; CSH HR = 1.46, 95% CI = 1.31 to 1.63). Grade, histological subtype, surgery utilization, and stage at diagnosis explained 24.4%, 20.1%, 18.4%, and 16.6% of the Black-White disparity in all-cause death, respectively. Although the cumulative incidence of all-cause death decreased, the Black-White gaps persisted in patients with endometrial cancer. Grade and histological subtype had the greatest influence. More efforts are needed to address the disparities.

History of heart failure and chronic kidney disease and the risk for all-cause death after COVID-19 during the three first waves in comparison to influenza outbreaks in Sweden

Abstract Background Infection with SARS-CoV-2 (COVID-19) affects people globally causing hospitalisation and reduced life expectancy. To improve future preventive measures there is a need of extensive analysis on contributing risk factors for severe COVID-19 outcome. Purpose To explore how cardiorenal disease (CRD; heart failure and/or chronic kidney disease) impacted mortality in patients hospitalised for COVID-19 during the three first waves in Sweden in comparison to previous influenza outbreaks and with a sex perspective. Methods All patients in Sweden with a main hospital diagnosis of COVID-19 (January 2020-September 2021) or influenza (January 2015-December 2019) with previous CRD were identified in registries and compared with a reference group free from CRD but with COVID-19 or influenza. Associated risk of all-cause death during the first year was analysed using adjusted Cox proportional hazards models. Results In COVID-19 patients with and without prior history of CRD (n=44,866) mean age was 79.8 years (SD 11.8) and 43% were women. In influenza patients (n=8897) mean age was 80.6 (SD 11.5) years and 45% were women. COVID-19 vs. influenza was associated with higher mortality risk the first two waves (HR 1.53; 95% CI 1.45–1.62, p&amp;lt;0.001 and 1.52; 1.44–1.61, p&amp;lt;0.001) but not in the third wave (1.07; 0.99–1.14, p=0.072). The cumulative incidence of all-cause death was increased in COVID-19 patients and in influenza patients if CRD was present (Figure 1). Further, CRD was an independent risk factor for all-cause death after COVID-19 in men and women (men: 1.37; 1.31–1.44, p&amp;lt;0.001, women: 1.46; 1.38–1.54, p&amp;lt;0.001). At ages &amp;lt;70 years women with CRD had a similar mortality rate as men with CRD while at ages ≥70 years mortality rate was higher in men (Figure 2). Conclusions Outcome after COVID-19 is worse if CRD is present. In women at ages &amp;lt;70 years the presence of CRD attenuates the protective effect of female sex. Further COVID-19 was associated with higher mortality risk than influenza during the first two waves. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The Family Kamprad FoundationAstraZeneca (study sponsor)

Deferral of Coronary Revascularization in Patients With Reduced Ejection Fraction Based on Physiological Assessment: Impact on Long-Term Survival.

Background Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all-cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all-cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR-guided group and 634 in the angiography-guided group). Median follow-up was 7 years (interquartile range, 3.22-11.08 years). After 1:1 propensity-score matching, baseline characteristics between the 2 groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49-0.85]; P<0.01). The rate of major adverse cardiovascular and cerebrovascular events was lower in the FFR-guided group (123 [59.7%] versus 139 [67.5%]; HR, 0.75 [95% CI, 0.59-0.95]; P=0.02). Conclusions In patients with reduced left ventricular ejection fraction, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and major adverse cardiovascular and cerebrovascular events at 10 years.

ST-elevation versus non-ST-elevation myocardial infarction after combined use of statin with renin-angiotensin system inhibitor: Data from the Korea Acute Myocardial Infarction Registry.

BackgroundLimited data are available comparing the combined effects of statins and renin–angiotensin system inhibitor (RASI) between patients with ST-segment elevation myocardial infarction (STEMI) and those with non-STEMI (NSTEMI). We compared the effects of statins combined with RASI in STEMI and NSTEMI patients after stent implantation during a 2-year follow-up period.MethodsA total of 21,890 acute myocardial infarction (AMI) patients who underwent successful stent implantation and who received statins with RASI were enrolled. They were separated into the STEMI group (n = 12,490) and the NSTEMI group (n = 9400). The major clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization.ResultsTwo propensity score-matched groups (5891 pairs, n = 11,782, C-statistic = 0.821) were generated. Even though the cumulative incidences of MACE, Re-MI, total repeat revascularization were similar between the two groups, the cumulative incidences of all-cause death (hazard ratio [HR] 1.407; 95% confidence interval [CI] 1.106–1.790; p = 0.005) and cardiac death (HR 1.311; 95% CI 0.983–1.749; p = 0.046) were significantly higher in the NSTEMI group.ConclusionsIn this study, statin with RASI combination therapy was more beneficial to the STEMI patients than to the NSTEMI patients in reducing all-cause death and cardiac death.

Impact of myocardial revascularization on long-term outcomes in a nationwide cohort of first acute myocardial infarction survivors.

The long-term clinical benefits of myocardial revascularization in a contemporary, nationwide cohort of acute myocardial infarction (AMI) survivors are unclear. We aimed to compare the mortality rates and clinical outcomes at 8 years of patients admitted in Italy for a first AMI managed with or without myocardial revascularization during the index event. This is a national retrospective cohort study that enrolled patients admitted for a first AMI in 2012 in all Italian hospitals who survived at 30 days. The outcomes of interest were all-cause mortality, major cardio-cerebrovascular events (MACCE), and re-hospitalization for heart failure (HF) at 8 years. Time to events was analysed using a Cox and Fine and Gray multivariate regression model. A total of 127 431 patients with AMI were admitted to Italian hospitals in 2012. The study cohort consisted of 62 336 AMI events, of whom 63.8% underwent percutaneous or surgical revascularization ≤30 days of the index hospital admission. At 8 years, the cumulative incidence of all-cause death was 36.5% (24.6% in revascularized and 57.6% in not revascularized patients). After multiple corrections, the hazard ratio (HR) for all-cause mortality in revascularized vs. not revascularized patients was 0.61 (P < 0.0001). The rate of MACCE was 45.7% and 65.8% (adjusted HR 0.83; P < 0.0001), while re-hospitalizations for HF occurred in 17.6% and 29.8% (adjusted HR 0.97; P = 0.16) in AMI survivors revascularized and not revascularized, respectively. In our contemporary nationwide cohort of patients at their first AMI episode, those who underwent myocardial revascularization within 1 month from the index event compared to those not revascularized presented an adjusted 39% risk reduction in all-cause mortality and 17% in MACCE at 8-year follow-up.