Cox Proportional Hazard Ratio Analysis Research Articles

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Clinicopathological Aspects and Inflammation-Immune Markers in Alcohol and/or Hepatitis C Virus-Induced Hepatocellular Carcinoma Patients Treated With Sorafenib.

Tyrosine kinase inhibitors have been used to treat hepatocellular carcinoma (HCC), but the outcomes of patients under treatment vary. Since the roles of clinicopathological aspects and markers of chronic inflammation/immune homeostasis in the outcome of HCC patients treated with sorafenib are still unclear, these were the aims of this study. Patients with alcohol-induced and/or hepatitis C virus (HCV)-induced HCC (n = 182) uniformly treated with sorafenib were included in the study. Baseline clinicopathological aspects of patients were computed from the medical records. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) were obtained from the hematological exam performed before the administration of sorafenib. Overall survival (OS) was analyzed using Kaplan-Meier probabilities, log-rank test, and univariate and multivariate Cox proportional hazard ratio (HR) analyses. In multivariate analysis, alpha-foetoprotein (AFP) level and Child-Pugh score were predictors of OS. Patients with AFP levels higher than 157 ng/mL and Child-Pugh B or C had 1.40 (95% confidence interval (CI): 1.03 - 1.91, P = 0.03) and 1.64 (95% CI: 1.07 - 2.52, P = 0.02) more chances of evolving to death than the remaining patients, respectively. NLR, PLR, LMR, SIRI, and SII did not alter the OS of HCC patients. AFP level and Child-Pugh score act as independent prognostic factors in patients with alcohol and/or HCV-induced HCC treated with sorafenib, but markers of chronic inflammation/immune homeostasis seem not to alter the outcome of patients with HCC induced by alcohol and/or HCV.

Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction.

Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2). In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events' predictive and discriminative ability through Harrell's C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories. In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

Osteoporotic Patients Undergoing Total Hip Arthroplasty Have a Similar 5-Year Cumulative Incidence Rate of Periprosthetic Fracture Regardless of Cemented Versus Cementless Femoral Stem Fixation

BackgroundIn osteoporotic patients, surgeons may utilize cemented femoral fixation to minimize risk of fracture. The purpose of this study was to compare 5-year implant survivability in patients who have osteoporosis who underwent elective total hip arthroplasty (THA) with cementless versus cemented fixation. MethodsA retrospective analysis of patients who have osteoporosis undergoing THA with either cemented or cementless femoral fixation was conducted using a national administrative claims database. Of the 18,431 identified THA patients who have osteoporosis, 15,867 (86.1%) underwent cementless fixation. The primary outcome was a comparison of the 5-year cumulative incidences of aseptic revision, mechanical loosening, and periprosthetic fracture (PPF). Kaplan–Meier and Multivariable Cox Proportional Hazard Ratio analyses were used, controlling for femoral fixation method, age, sex, a comorbidity scale, use of osteoporosis medication, and important comorbidity. ResultsThere was no difference in aseptic revision (Hazard’s Ratio (HR): 1.13; 95% Confidence Interval (CI): 0.79 to 1.62; P value: .500) and PPF (HR: 0.96; 95% CI: 0.64 to 1.44; P value: .858) within 5 years of THA between fixation cohorts. However, patients who had cemented fixation were more likely to suffer mechanical loosening with 5 years post-THA (HR: 1.79; 95% CI: 1.17 to 2.71; P-value: .007). ConclusionsWe found a similar 5-year rate of PPF when comparing patients who underwent cementless versus cemented femoral fixation for elective THA regardless of preoperative diagnosis of osteoporosis. While existing registry data support the use of cemented fixation in elderly patients, a more thorough understanding of the interplay between age, osteoporosis, and implant design is needed to delineate in whom cemented fixation is most warranted for PPF prevention.

A long-term prognostic factor for cardiovascular risk in patients with chest pain without diabetes mellitus and significant coronary stenosis

Abstract Background Chest pain is the most common symptom of coronary artery disease (CAD); diabetes mellitus (DM) is a well-known single largest risk factor for cardiovascular diseases and survival worldwide. So, the impact of CAD and DM on long-term clinical effects is reported widely. This study aimed to evaluate the long-term prognostic factor for major adverse cardiac and clinical events (MACCE) in patients with chest pain without DM and CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation test. Methods A total of 1,046 patients with chest pain without DM and significant CAD who underwent CAG and ACH tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. All subjects were followed clinically for up to 5 years. Results Coronary spasm (CAS) seems the most common cause of chest pain. However, long-term MACCE of CAS is not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a repeated chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year follows, MACCE has occurred 7.3%, including recurrent angina of 6.9%. Dyslipidemia, mild to moderate CAD, and the use of aspirin/nitrates are associated with long-term MACCE. Conclusions Among the patients with chest pain without DM and significant CAD, the occurring major adverse cardiac events, including death, MI, and de novo CAD, are rare, but recurrent angina is still a challenging problem who had the treatment by anti-anginal medications.

Abstract 16620: Long-Term Prognostic Factors for Cardiovascular Events in Patients With Chest Pain Without Diabetes Mellitus and Significant Coronary Stenosis

Background: Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD and DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. Methods: A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiovascular events (MACE) were defined as the composite of total death, myocardial infarction (MI), and revascularization. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of MACE, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Results: Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a recurrent chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia, ICS, the use of aspirin and nitrates were associated with long-term MACCE. Conclusions: Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with anti-anginal medications.

O008 Refining the Hypoxic Burden Algorithm by Investigating different Methods for Calculating the SpO2 Baseline

Abstract Introduction Intermittent hypoxia is a key mechanism linking Obstructive Sleep Apnoea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. The hypoxic burden (HB) is a measure calculated from the oximetry signal that shows promise for predicting CVD mortality, but its calculation is complex. With a view to simplifying its calculation, we investigated three different baseline calculation methods and its impact on predicting CVD mortality for the HB algorithm. Methods Data from Sleep Heart Health Study (SHHS) with CVD mortality outcome and complete covariate information was used. We implemented the HB method of Azarbarzin et al 2018 ERJ. The three baseline methods included an event-based baseline (same as Azarbarzin et al 2018 ERJ), a record-based baseline, and a fixed baseline. The performance of each parameter in predicting CVD mortality was assessed using an adjusted Cox proportional hazard ratio (HR) analysis. Results The best performing method was the record-based baseline method which returned a fully adjusted model hazard ratio of 1.83 (95% CI: 1.03-3.27, p&amp;lt;0.05). The results for the event-based and record-based baseline methods were 1.60 (95% CI: 0.86-3.00, p=0.14) and 1.73 (95% CI: 0.93-3.22, p=0.08) respectively. Discussion HB with the record-based baseline was easier to calculate than the original event-based baseline method by Azarbarzin at al. and resulted in improved CVD mortality prediction performance. We believe that this method provides a step towards providing a novel parameter with easy calculation providing early risk stratification in cardiovascular patients.

Risk factors for mortality in severe COVID-19: Exploring the interplay of immunomodulatory therapy and coinfection.

Patients with severe clinical manifestations of coronavirus disease 2019 (COVID-19) present particular diagnostic and management challenges to critical care physicians, including identifying and responding to concurrent bacterial and fungal coinfections. This study evaluates risk factors for in-hospital mortality in patients admitted to the intensive care unit with severe COVID-19 during circulation of the B.1.617.2 (Delta) variant, including the impact of immunomodulators and bacterial and/or fungal coinfection. This retrospective cohort study enrolled patients with severe COVID-19. A Cox proportional hazard ratio analysis identified risk factors for in-hospital mortality. Outcomes were also compared between patients receiving and not receiving immunomodulatory therapy alongside standard care. Ninety patients admitted to the intensive care unit were enrolled. On multivariate analysis, the greatest risk factors for in-hospital mortality were invasive mechanical ventilation (hazard ratio (HR) = 15.27; 95% confidence interval (CI) 3.29-71.0; P < 0.001), elevated body mass index (HR = 1.07 per unit; 95% CI 1.02-1.13; P = 0.007) and older age (HR = 1.53 per decade; 95% CI 1.05-2.24; P = 0.028). Bacterial and/or fungal coinfection occurred at equal frequency in patients receiving and not receiving immunomodulatory therapy. However, in patients receiving immunomodulators, coinfection carried a significantly higher mortality risk (63.0%) compared with those without coinfection (15.4%; P = 0.038). Mortality from severe COVID-19 is significantly higher in older patients and those with elevated body mass index and requiring mechanical ventilation. Immunomodulatory therapy necessitates vigilance towards evolving coinfection in the intensive care setting.

Prognostic Value of Hematological Markers in Head and Neck Cancer Patients With a History of Hematological Malignancy

Background and Objectives Head and neck cancer can occur as a second primary tumor in patients with a history of hematological malignancy, and the pathological features of those are more aggressive than de novo primary head and neck cancer. However, research related to the prognostic value of hematological markers in the head and neck cancer patients with a history of hematological malignancy is scarce, so we performed this study.Subjects and Method We reviewed a total of 89 head and neck cancer patients with hematological malignancy diagnosed at a single tertiary hospital between 1997 and 2021, and enrolled 29. The analyzed hematological parameters included pre- and post-treatment hemoglobin, hematocrit, lactate dehydrogenase, absolute neturophil count (ANC), absolute platelet count, absolute leukocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio.Results Hematological malignancy was diagnosed almost 62.14±96.10 months before head and neck cancer. The most common hematological malignancy was acute myeloid leukemia. The overall survival (OS) rate was lower in patients with second primary tumor than in those with de novo primary head and neck cancer. The cox-proportional hazard ratio analysis showed that the post-treatment absolute neutrophil count was significantly correlated with disease-free survival but not with OS.Conclusion The post-treatment hematological profile, particularly ANC, can be considered a useful prognostic marker in the head and neck cancer patients with a history of hematological malignancy.

The impact of prior fragility fractures on long-term periprosthetic fracture risk following total knee arthroplasty.

The aim of this study was to characterize the association of prior FFs on long-term risk of secondary fragility fracture (FF), periprosthetic fracture (PPF), and revision TKA. Patients at least 50years of age who underwent elective TKA were identified in the PearlDiver Database. Patients were stratified based on whether they sustained a FF within 3years prior to TKA (7410 patients) or not (712,954 patients). Demographics and comorbidities were collected. Kaplan Meier analysis was used to observe the cumulative incidence of all-cause revision, PPF, and secondary FF within 8years of TKA. Cox Proportional hazard ratio analysis was used to statistically compare the risk. In total, 1.0% of patients had a FF within three years of TKA. Of these patients, only 22.6% and 10.9% had a coded diagnosis of osteoporosis and osteopenia, respectively, at time of TKA. The 8-year cumulative incidence of secondary FF and periprosthetic fracture was significantly higher in those with a prior FF (27.5% secondary FF and 1.9% PPF) when compared to those without (9.1% secondary FF and 0.7% PPF). After adjusting for covariates, patients with a recent FF had significantly higher risks of secondary FF (HR 2.73; p < 0.001) and periprosthetic fracture (HR 1.86; p < 0.001) than those without a recent FF. Recent FF before TKA is associated with increased risk for additional FF and PPF within 8years following TKA. Surgeons should ensure appropriate management of fragility fracture is undertaken prior to TKA to minimize fracture risk, and if not, be vigilant to identify patients with prior FF or other bone health risk factors who may have undocumented osteoporosis.

Repercussions of absolute and time-rated BMI "yo-yo" fluctuations on cardiovascular stress-related morbidities within the vascular-metabolic CUN cohort.

The association between body mass index (BMI) fluctuation and BMI fluctuation rate with cardiovascular stress morbidities in a Caucasian European cohort was evaluated to ascertain the impact of weight cycling. A total of 4,312 patients of the Vascular-Metabolic CUN cohort (VMCUN cohort) were examined and followed up during 9.35 years ( ± 4.39). Cox proportional hazard ratio analyses were performed to assess the risk of developing cardiovascular stress-related diseases (CVDs) across quartiles of BMI fluctuation, measured as the average successive variability (ASV) (ASV = |BMIt0 - BMIt1| + |BMIt1 - BMIt2| + |BMIt2-BMIt3| +…+ |BMItn - 1 - BMItn|/n - 1), and quartiles of BMI fluctuation rate (ASV/year). There were 436 incident cases of CVD-associated events involving 40,323.32 person-years of follow-up. A progressively increased risk of CVD in subjects with greater ASV levels was found. Also, a higher level of ASV/year was significantly associated with an increased risk of developing CVD stress independent of confounding factors with a value of 3.71 (95% CI: 2.71-5.07) for those in the highest quartile and 1.82 (95% CI: 1.33-2.50) for those in the third quartile. The BMI fluctuation rate seems to be a better predictor than BMI fluctuation of the potential development of cardiovascular stress morbidities. The time-rated weight fluctuations are apparently more determinant in increasing the risk of a CVD than the weight fluctuation itself, which is remarkable in subjects under "yo-yo" weight patterns for precision medicine.

BIOS-03. REAL WORLD CLINICAL OUTCOMES OF PATIENTS WITH DIFFUSE MIDLINE GLIOMA IN A LONGITUDINAL OUTCOMES REGISTRY

Abstract We utilized the longitudinal clinical outcomes registry XCELSIOR (NCT03793088) to understand real world outcomes and treatment patterns among patients with diffuse midline glioma. A total of 74 patients were identified with a diagnosis of diffuse midline glioma by pathology or imaging (36 pediatric and 38 adult patients). Median age at diagnosis was 20 years. As of 6/1/2022, 45 patients had expired. Median overall survival (mOS) of the entire cohort was 16.2 months. Cox proportional hazard ratio analysis identified age as the only significant covariate for OS (pediatric HR = 1.59, p=0.04). Pediatric patients had a mOS of 12.9 months and adult patients a mOS of 18.9 months from diagnosis. Frequency of primary tumor location in this dataset was brainstem (35%), thalamus (23%), and pons (20%). Pons location was associated with worst survival (mOS 11.4 months, n=15 patients). The most common anti-cancer interventions among all patients were ONC201 (39 patients), temozolomide (37 patients), bevacizumab (23 patients), panobinostat (8 patients), and immune checkpoint inhibitors (3 patients each, pembrolizumab and nivolumab). In this dataset, no interventions were statistically significant in a Cox proportional hazard model, but both immune checkpoint inhibitors (HR = -1.24, p=0.11) and ONC201 (HR = -0.38, p=0.27) trended toward benefit in the entire population. The subpopulation of patients treated with ONC201 whose tumor also harbored a TP53 mutation displayed a tendency toward activity (n=8); TP53-mutant patients treated with ONC201 had a mOS of 25.0 months vs. TP53 wild-type patients treated with ONC201 had a mOS of 20.3 months. Annotation of data for additional patients is ongoing and updated analyses will be presented at the meeting.

O073 Traditional Clinical and Novel Oximetry Measures as Predictors of Cardiovascular Events

Abstract Introduction Intermittent hypoxia is a key mechanism linking Obstructive Sleep Apnoea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. We investigated if traditional clinical and novel oximetry measures including hypoxic burden (HB) calculated from the polysomnogram SpO2 signal can predict CVD outcomes in all-comers and OSA subsample cohorts from the Sleep Heart Health Study (SHHS). Methods CVD mortality outcome and complete covariate information was used. We implemented 31 oximetry measures and assessed the performance of the parameters in predicting CVD outcomes (CVD death or incident CVD) in the all-comers and sleep apnoea subsamples. The performance of each measure was assessed using an adjusted Cox proportional hazard ratio (HR) analysis. Results In the general subsample, HB successfully predicted CVD death (HR&amp;gt;1.8, p&amp;lt;0.05) but did not predict incident CVD. In the sleep apnoea subsample (AHI&amp;gt;5) with no CVD at baseline, none of the SpO2 measures we considered predicted incident CVD. Discussion The ability of HB to predict CVD outcomes depends on the cohort and the CVD outcome. Our analysis of the selected SpO2 measures in an OSA subsample did not find strong links between any oximetry measures and incident CVD, and therefore no strong candidates for CVD risk phenotyping in the sleep clinic. Further work is needed to understand the complex relationship between OSA-related intermittent hypoxia patterns and development of CVD to further understanding of OSA phenotypes at risk of CVD consequences.

Neither Tumor-Infiltrating Lymphocytes nor Cytotoxic T Cells Predict Enhanced Benefit from Chemotherapy in the DBCG77B Phase III Clinical Trial.

Simple SummaryApart from the direct killing of cancer cells, cyclophosphamide-based chemotherapy has been shown to induce an antitumor immune response, and is being used in combination with immunotherapies in cancer care. We assessed the interaction of chemotherapy with immune biomarkers expressed on primary tumor tissue from a randomized phase III clinical trial, and confirmed that the presence of tumor-infiltrating lymphocytes is linked to improved survival in premenopausal women with high-risk breast cancer, regardless of their treatment allocation. However, immune biomarkers including tumor-infiltrating lymphocytes do not predict extra benefit from cyclophosphamide chemotherapy. This finding applies across the major molecular subgroups, including non-luminal and basal breast cancers that tend to be more immunogenic, and are often considered the most suitable subsets for receiving immunotherapy.Recent studies have shown that immune infiltrates in the tumor microenvironment play a role in response to therapy, with some suggesting that patients with immunogenic tumors may receive increased benefit from chemotherapies. We evaluated this hypothesis in early breast cancer by testing the interaction between immune biomarkers and chemotherapy using materials from DBCG77B, a phase III clinical trial where high-risk premenopausal women were randomized to receive chemotherapy or no chemotherapy. Tissue microarrays were evaluated for tumor-infiltrating lymphocytes (TILs) assessed morphologically on hematoxylin and eosin-stained slides, and by immunohistochemistry for CD8, FOXP3, LAG-3, PD-1 and PD-L1. Following REMARK reporting guidelines, data analyses were performed according to a prespecified statistical plan, using 10-year invasive disease-free survival as the endpoint. Differences in survival probabilities between biomarker groups were evaluated by Kaplan–Meier and Cox proportional hazard ratio analyses and prediction for treatment benefit by an interaction test. Our results showed that stromal TILs were associated with an improved prognosis (HR = 0.93; p-value = 0.03), consistent with previous studies. However, none of the immune biomarkers predicted benefit from chemotherapy in the full study set nor within major breast cancer subtypes. Our study indicates that primary tumors with higher immune infiltration do not derive extra benefit from cyclophosphamide-based cytotoxic chemotherapy.

Determinants of Non-calcified Low-Attenuation Coronary Plaque Burden in Patients Without Known Coronary Artery Disease: A Coronary CT Angiography Study

BackgroundAlthough epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD), it is unclear whether EAT volume (EAV) can be used to diagnose high-risk coronary plaque burden associated with coronary events. This study aimed to investigate (1) the prognostic impact of low-attenuation non-calcified coronary plaque (LAP) burden on patient level analysis, and (2) the association of EAV with LAP volume in patients without known CAD undergoing coronary computed tomography angiography (CCTA).Materials and MethodsThis retrospective study consisted of 376 patients (male, 57%; mean age, 65.2 ± 13 years) without known CAD undergoing CCTA. Percent LAP volume (%LAP, <30 HU) was calculated as the LAP volume divided by the vessel volume. EAT was defined as adipose tissue with a CT attenuation value ranging from −250 to −30 HU within the pericardial sac. The primary endpoint was a composite event of death, non-fatal myocardial infarction, and unstable angina and worsening symptoms requiring unplanned coronary revascularization >3 months after CCTA. The determinants of %LAP (Q4) were analyzed using a multivariable logistic regression model.ResultsDuring the follow-up period (mean, 2.2 ± 0.9 years), the primary endpoint was observed in 17 patients (4.5%). The independent predictors of the primary endpoint were %LAP (Q4) (hazard ratio [HR], 3.05; 95% confidence interval [CI], 1.09–8.54; p = 0.033] in the Cox proportional hazard model adjusted by CAD-RADS category. Cox proportional hazard ratio analysis demonstrated that %LAP (Q4) was a predictor of the primary endpoint, independnet of CAD severity, Suita score, EAV, or CACS. The independent determinants of %LAP (Q4) were CACS ≥218.3 (p < 0.0001) and EAV ≥125.3 ml (p < 0.0001). The addition of EAV to CACS significantly improved the area under the curve (AUC) to identify %LAP (Q4) than CACS alone (AUC, EAV + CACS vs. CACS alone: 0.728 vs. 0.637; p = 0.013).ConclusionsCCTA-based assessment of EAV, CACS, and LAP could help improve personalized cardiac risk management by administering patient-suited therapy.

Comparative Influence of Primary Healthcare Payer Types on Patient Outcomes After Lung Transplantation

<h3>Purpose</h3> Optimal outcomes in patients undergoing lung transplantation requires significant utilization of resources. We, therefore, evaluated the association of primary payer type with outcomes after lung transplantation. <h3>Methods</h3> Using the UNOS (United Network for Organ Sharing) registry we studied 15129 first-time lung transplant recipients from January 2000 to December 2017 and compared all-cause mortality at 1 year. Single lung (N=4524) and double lung (N=10605) recipients were subgrouped by payer type: Medicaid (32% and 27% respectively), Medicare (26% and 18%), and commercial insurance (42% and 54%). <h3>Results</h3> Primary payer type was not significantly associated with inferior outcomes at 1 year following both single-lung (P=0.447) and double lung transplant (P=0.531). Insurance was also not a predictor of worse outcomes following single lung transplant after 3 years (P=0.107). However, insurance type was associated with different outcomes in double lung recipients at 3 years (P=0.028) and remained significant predictors of early mortality after adjustment for covariates in multivariate Cox proportional hazard ratio analyses (P<0.05). <h3>Conclusion</h3> These data are among the first to provide insight into the impact of insurance status on patient outcomes for a modern cohort of lung transplant recipients. All-cause mortality after single-lung and double-lung transplantation did not differ significantly by payer type after 1 year. However, primary payer type was associated with 3-year outcomes following double lung transplant. More research is needed to confirm and define the reasons for insurance type playing a role in outcomes after double lung transplant as compared to single lung transplant.

Secondary interventions after fenestrated/branched aneurysm repairs are common and nondetrimental to long-term survival

ObjectiveSecondary interventions are common after endovascular repair of aortic aneurysms. However, the frequency and procedural details of secondary interventions after fenestrated or branched endovascular abdominal aortic aneurysm repair (F/BEVAR) have been less well described, and the effects on long-term survival and aneurysm-related mortality are unknown. MethodsConsecutive patients enrolled as a part of a multicenter research consortium in nine independent physician-sponsored investigational device exemption studies from 2005 to 2020 were evaluated. All secondary interventions performed after the initial procedure were classified as open or percutaneous and as major or minor in accordance with the Society for Vascular Surgery reporting standards. Secondary interventions were further classified as high or low magnitude according to the physiologic effects of the intervention. The demographics, procedural details, and perioperative outcomes were compared between those who had and those who had not undergone secondary interventions. Kaplan-Meier and Cox proportional hazard ratio (HR) analysis were used to evaluate long-term survival. ResultsOf 1681 patients who had undergone F/BEVAR, 385 (23%) had required a secondary intervention at any point during follow-up. Freedom from reintervention was 82% at 1 year and 59% at 5 years of follow-up. The mean follow-up period was 23 months. Most secondary interventions were percutaneous (84%), minor (70%), and of low magnitude (81%). Renal stenting (30%) and access-related procedures (24%) were the most frequent percutaneous and open procedures, respectively. High magnitude operations were required for 19% of the patients. Technical success was achieved for 94% of the secondary interventions, and mortality from the secondary interventions was <1%. Secondary interventions as a whole were associated with improved long-term survival (HR, 0.6; 95% confidence interval [CI], 0.5-0.7). In the subgroup analysis, major (HR, 0.6; 95% CI, 0.4-0.8), minor (HR, 0.6; 95% CI, 0.5-0.8), low magnitude (HR, 0.5; 95% CI, 0.4-0.7), and percutaneous (HR, 0.6; 95% CI, 0.5-0.7) secondary interventions were associated with improved survival. However, high magnitude (HR, 1.0; 95% CI, 0.7-1.5) and open (HR, 1.0; 95% CI, 0.7-1.5) secondary interventions were not. Similarly, when aneurysm-related survival was specifically assessed, low magnitude secondary interventions were found to improve survival (HR, 0.3; 95% CI, 0.1-0.7), and high magnitude secondary interventions (HR, 2.8; 95% CI, 1.4-5.8) and open secondary interventions (HR, 2.7; 95% CI, 1.3-5.5) were associated with increased mortality. ConclusionsSecondary interventions after F/BEVAR were frequent and were typically percutaneous, minor, and low magnitude procedures. Although uncommon, high magnitude and open secondary interventions were associated with decreased long-term survival and increased aneurysm-related mortality. These data highlight the importance of close, lifelong surveillance and suggest that a significant rate of secondary intervention should be anticipated but that these will not negatively affect survival.

RV free wall longitudinal strain as an independent predictor of survival in wtATTR-CA patients

Abstract Background Wild type transthyretin cardiac amyloidosis (wtATTR-CA) is increasingly recognized as a cause of heart failure with preserved ejection fraction (HFpEF) but prognosis is often limited due to late or misdiagnosis.Longitudinal left ventricular strain and biomarkers are established as markers of disease severity, but the role of RV free wall strain, reflecting RV contractility, is less well understood. Purpose We sought to determine whether RV free wall strain might add incremental prognostic value in wtATTR-CA. Methods Consecutive patients diagnosed with wtATTR-CA with tissue confirmation at Mayo clinic between 2013 and 2015 were included. Patients with TTR gene mutations were excluded. Baseline characteristics and transthoracic echocardiography measurements were obtained from the medical records. Speckle tracking RV free wall longitudinal 2D strain and peak LA longitudinal 2D strain were measured using Tom Tec Imaging System. Survival was determined using Kaplan Meier estimates and using the cox proportional hazard ratio, univariate and multivariable analysis were performed to identify predictors of mortality in patients with wtATTR. Results The study group comprised 139 patients (mean age 74.9±8.6, 92.8% male), of which 102 had adequate image quality for RV strain, and 99 for LA strain. Amongst these, 102 (73.3%) had AF and 118 patients (84.8%) had HF. During 3.23±2.0 years of follow up, 66 patients died. Both mean RV and LA strain were impaired at baseline: RV free wall strain was −14.7±4.9, and peak atrial longitudinal strain (PALS) was 13.2±8.8%. Using ROC analysis, RV strain of −16.8% was an independent predictor of all-cause mortality. In univariate modeling, higher levels of NT-proBNP (HR: 1.1 per 1000 pg.ml; 95%, CI 1.05–1.15, p&amp;lt;0.001) and Troponin T (HR: 2.0 per 0.1ng/ml; 95% CI 1.49–2.61, p&amp;lt;0.001) were associated with increased all-cause mortality. In addition, LV GLS (HR: 1.13 per 1%; 95% CI1.04–1.24, p=0.003), RV free wall LS (HR: 2.16 per 5%; 95%, CI 1.57–3.03, p&amp;lt;0.0001), and PALS (HR: 0.91 per1%; 95% CI 0.85–0.96, p&amp;lt;0.0001) were univariate predictors of all-cause mortality. In multivariate analysis using a stepwise regression model, RV free wall longitudinal strain (HR: 1.81; 95% CI 1.29–2.62, p&amp;lt;0.001) and Troponin T (HR: 1.7; 95% CI 1.25–2.26, p=0.001) remained independent predictors. Kaplan-Meier survival analysis demonstrated a higher mortality rate above −16.8 RV strain cut-off (Wilcoxon &amp;lt;0.0001). All stages were divided into two groups by −16.8% RV strain, and survival in individual stages analyzed. Stage 1 and 2 with &amp;lt;−16.8 RV free wall strain value had higher mortality than ≤-16.8% RV strain (Stage 1: Wilcoxon = 0.0041 and Stage 2: Wilcoxon = 0.023). However, there was not a survival difference between two RV strain groups in stage3 (Wilcoxon = 0.34) Conclusion RV free wall strain is an independent predictor of survival in wtATTR patients and may add incremental prognostic value to NT-proBNP and Troponin. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier curve of all patientsKaplan-Meier curve of stages

O036 Respiratory event related oxygen desaturation is predictive of cardiovascular mortality in sleep apnoea patients

Abstract Introduction Cardiovascular disease (CVD) is the leading cause of death globally. The mechanisms underpinning the development of CVD in OSA are multifaceted and include sympathetic overactivity, endothelial dysfunction, inflammation, and oxidative stress. Nocturnal hypoxaemic burden—the cumulative exposure to hypoxaemia experienced overnight—may contribute to the pathophysiology of CVD. We investigated if polysomnogram SpO2 parameters can predict CVD outcomes in OSA patients. Methods Data from the SpO2 signals from 4689 polysomnograms (PSGs) of the Sleep Heart Health Study with CVD mortality outcome and complete covariate information was used. Analysis of the average SpO2 responses to respiratory events revealed a transient response from the event start that extended for four event lengths. Based on the response we developed a respiratory event related oxygen desaturation (REROD) parameter for quantifying the desaturation associated with respiratory events that is readily calculated. The performance of the parameter in predicting CVD death was assessed using an adjusted Cox proportional hazard ratio (HR) analysis and compared to other methods including hypoxic burden, T90 and ODI3. Results The COX analysis was adjusted for known covariates of CVD. The HR results indicate a dose-response relationship with the highest quintile providing a HR=2.0(95% C.I. 1.3–3.2). Discussion Our REROD metric predicts CVD mortality independent of confounding covariates and provides prediction performance superior to other hypoxemia metrics. A big advantage of our metric is its computational simplicity and reproducibility. We believe the metric is an important enabling step towards clinical methods that provide CVD risk stratification from the PSG.

A nuclear polymorphism at the 8q24 region is associated with improved survival time and chemo-response in high-grade serous ovarian cancer.

The 8q24 chromosomal region is strongly associated with an increased risk of ovarian cancer. One single nucleotide polymorphism that is associated with ovarian cancer in this region is rs6983267, located within the long non-coding RNA colon cancer associated transcript 2 (CCAT2). The aim of the present study was to assess the association between rs6983267 and clinical outcomes in patients with high-grade serous ovarian cancer (HGSOC). The present retrospective genetic association study utilized Sanger sequencing to determine the genotype at the rs6983267 locus (GG, GT, TT) in 98 patients with HGSOC. Survival time and chemotherapy responses between patients were compared with the TT genotype and patients with a genotype containing a G allele (GT, GG). Survival analyses were performed using Cox proportional hazard ratio analysis. Association with chemo-response was performed using a logistic regression. The results revealed that patients with HGSOC and the TT genotype at the rs6983267 locus had improved survival time compared with patients with genotypes containing a G allele [hazard ratio=0.59; 95% confidence interval (CI), 0.36–0.97; P=0.039] and were significantly associated with International Federation of Gynecology and Obstetrics stage [odds ratio (OR)=5.34; 95% CI, 1.50–22.62; P=0.014] and positive chemo-response (OR=4.51; 95% CI, 1.40–18.00; P=0.018). In summary, patients with HGSOC and the TT genotype at the rs6983267 locus had improved survival time compared with those with a G allele, despite being associated with more advanced disease; this was possibly due to an improved response to chemotherapy.