1-year All-cause Mortality Research Articles

OGC O06 - Socioeconomic Health Inequality in Oesophago-gastric Cancer in a Single Tertiary Centre: On Behalf of Greater Manchester OG Unit

Abstract Background Oesophagogastric cancer (OGC) 5-year survival is poor (15%). Only 34% of patients are considered for potentially curative treatment, which is associated with a 41% chance of survival. In other cancer, deprivation is associated with poor outcomes. This study aims to determine the association between deprivation, tumour and treatment intent (TI), and 5-year all-cause mortality (M) in OGC. Method This retrospective cohort study analysed patients newly diagnosed with OGC (adenocarcinoma or squamous cell carcinoma) across Greater Manchester between January 2018 and January 2023. TI was defined as the treatment pathway, at completion of staging investigations, either curative (pathway to resection or definitive chemoradiotherapy) or palliative (best supportive care, palliative chemotherapy or radiotherapy). Statistical analysis encompassed methods such as binary logistic regression, Cox proportional hazards models and Kaplan-Meier survival curves with adjustments made for age, gender, and clinical stage. IMD scores were grouped from deciles into quintiles leaving 5 groups, with IMD1 representing the most deprived. Results 3027 patients were included (2102, 69.4% males). Patients in IMD1 were diagnosed 4 years younger than in IMD5 (most affluent) (median age 70 (IQR=17) vs 74 (IQR=16), p<0.001). There was a higher proportion of deprived patients (32.9% IMD1 vs 15.3% IMD5, p<0.001). The proportion of stage 4b disease in IMD1 compared with IMD5 was not different (406 (40.7%) vs 174 (37.5%), p=0.081). The median survival was lower in IMD1 compared with IMD5 (0.81 vs 0.90 years, p=0.074). Following adjustment for confounders IMD1 was associated with a poorer overall survival when compared with IMD5 (HR 1.16, CI[1.02-1.32],p=0.020). Conclusion This study highlights a significant health inequality in the outcomes of OGC. Poorer outcomes in the most deprived group were independent of tumour stage, gender and age. Urgent measures to address socioeconomic health inequalities need to be instigated.

Abstract 4132498: Hemodynamic and Clinical Outcomes with Balloon-Expandable Valves Versus Self-Expanding Valves in Patients with Small Aortic Annulus Undergoing Transcatheter Aortic Valve Implantation: A Meta-Analysis of Randomized Controlled Trials and Propensity Score Matched Studies

Background: Transcatheter aortic valve implantation (TAVI) is thought to be more effective than surgery for patients with small aortic annulus (SAA), however, the comparative efficacy of different transcatheter heart valves (THVs) remains uncertain. The objective of this meta-analysis was to compare the effects of balloon-expandable valves (BEVs) and self-expanding valves (SEVs) on hemodynamic parameters and clinical outcomes in patients with SAA who underwent TAVI. Methods: A thorough literature search was performed across PubMed/MEDLINE, Embase, and the Cochrane Library from their inception until May 2024 to identify eligible randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Clinical outcomes were evaluated using a random-effects model to pool risk ratios (RRs) with 95% confidence intervals (CIs). Results: The analysis included 8 studies; 2 RCTs and 6 PSM studies, with a total of 2,180 patients with SAA. BEVs were associated with a smaller indexed effective orifice area (MD: -0.18, 95% CI: -0.31 to -0.05) and a higher transvalvular mean pressure gradient (MD: 5.23, 95% CI 3.44 to 7.02) than SEVs. The risk for prosthesis-patient mismatch (PPM) (RR= 1.82, 95% CI: 1.27 to 2.60) and severe PPM (RR= 2.77, 95% CI: 1.93 to 3.98) was significantly higher for patients receiving BEVs than those receiving SEVs. However, no significant difference was observed between BEVs and SEVs regarding the risk of paravalvular leak (RR= 0.98, 95% CI: 0.57 to 1.69) and the permanent pacemaker implantation (RR= 0.78, 95% CI: 0.50 to 1.23). Although patients receiving BEVs showed a slightly lower risk of major bleeding events (RR= 0.69, 95% CI: 0.49 to 0.99), BEVs were associated with a significantly increased risk of 1-year cardiovascular mortality (RR= 1.61, 95% CI: 1.05 to 2.47) compared to those receiving SEVs. However, no significant differences were observed between BEVs and SEVs regarding 30-day all-cause mortality (RR= 1.19, 95% CI: 0.57 to 2.49), 1-year all-cause mortality (RR= 1.17, 95% CI: 0.89 to 1.53), stroke rates (RR= 0.83, 95% CI: 0.52 to 1.31) and any vascular complication (RR= 1.13, 95% CI: 0.72 to 1.75). Conclusion: In patients with SAA, SEVs showed reduced risks of PPM and severe PPM compared to BEVs, along with a larger indexed effective orifice area. Moreover, SEVs were associated with a lower risk of 1-year cardiovascular mortality.

Abstract 4119146: Pulmonary Artery Enlargement Predicts Mortality in Patients with Severe Aortic Stenosis after Transcatheter Aortic Valve Replacement.

Background: Pulmonary hypertension is associated with extensive remodeling of the pulmonary tree, with key finding the enlargement of the pulmonary artery (PA). Although the independent predictive value of the pulmonary hypertension in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis has been clearly demonstrated, data about the potential predictive value of the pre-interventional PA enlargement on mortality are scarce. Research questions: The aim of the present study was to assess the prognostic significance of the pre-interventional PA enlargement, assessed by cardiac CT scan, in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis. Methods: We conducted a retrospective study and recruited 337 patients with aortic stenosis, who underwent a right heart catheterization and a cardiac CT scan before the transcatheter aortic valve replacement. The cohort was divided in two groups according to the presence of an enlarged PA (PA e ), (main PA axial diameter ≥ 29 mm for males and ≥ 27 mm for females, n=192, mean age 83±6 years, 41% males) or not (PA n ), ( n=145, mean age 84±6 years, 46% males). The primary endpoint was all-cause mortality at 1 year. Results: Globally, a strong correlation between invasive mean PA pressure and main PA axial diameter was noted (Pearson r=0.393, p<0 .001). Compared to the PA n group, patients with enlarged PA exhibited higher 1 year mortality rates (hazard ratio 2.51, 95% CI: 1.1-6.04, p=0.027). The prognostic significance was even stronger after indexing the PA to the ascending aorta diameter (hazard ratio 3.82, 95% CI: 1.86-7.87, p<0.001, figure 1). Conclusions: Pre interventional PA enlargement, is strongly associated with 1-year all-cause mortality in patients undergoing transcatheter aortic valve. This may pave the way for a more precise non-invasive risk stratification in patients with severe aortic stenosis.

Clip It or Let It: The Efficacy of Mitral Valve Transcatheter Edge-to-Edge Repair Versus Conservative Treatment in Reducing Mortality Among Patients With Ischemic Mitral Regurgitation

BACKGROUND: Despite revascularization and optimal medial therapy (OMT) residual ischemic mitral regurgitation (IMR) continues in a self-aggravating vicious cycle to affect prognosis and survival adversely. Mitral valve surgery in combination with coronary artery bypass graft remains a subject of debate due to the absence of a net overall benefit. Mitral valve transcatheter edge-to-edge repair (M-TEER) has been gaining grounds as a viable option from observational studies, but results from randomized controlled trials (RCTs) have yielded mixed results. Thus, this study was conducted to determine whether the current collective data support the efficacy of M-TEER with OMT versus OMT alone in patients with clinically significant IMR. METHODS: A literature search from PubMed/MEDLINE, Cochrane Review Central, Clinical Trials Registry, ResearchGate, Mendeley, and Google Scholar for relevant RCTs and observational studies was conducted and reviewed independently by three reviewers. Published and unpublished studies indexed from inception until 2023 were included. The pooled estimates for the primary outcome of all-cause mortality and secondary outcomes of cardiac mortality and heart failure hospitalizations were measured using R Studio statistical software (R Foundation forStatistical Computing, Vienna, Austria). RESULTS: Seven eligible studies (five observational and two RCTs) allocated 1610 IMR patients to M-TEER + OMT (n = 942) or OMT alone (n = 668). The effect estimate using random-effects model demonstrated M-TEER with OMT to significantly reduce 1-year (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.52–0.86; P = 0.002) and 2-year (OR, 0.50; 95% CI, 0.38–0.67; P < 0.00001) all-cause mortality. Cardiac mortality (OR, 0.58; 95% CI, 0.27–1.23; P = 0.15) and heart failure hospitalization (OR, 0.45; 95% CI, 0.18–1.13; P = 0.09) did not reach statistical significance between the treatment arms. CONCLUSION: In patients with IMR, M-TEER on top of OMT was able to afford a 2-year allcause mortality advantage. KEYWORDS: ischemic mitral regurgitation, mitral valve transcatheter edge-to-edge repair, optimal medical therapy

Calcific Aortic Stenosis: A Review.

Calcific aortic stenosis (AS) restricts the aortic valve opening during systole due to calcification and fibrosis of either a congenital bicuspid or a normal trileaflet aortic valve. In the US, AS affects 1% to 2% of adults older than 65 years and approximately 12% of adults older than 75 years. Worldwide, AS leads to more than 100 000 deaths annually. Calcific AS is characterized by aortic valve leaflet lipid infiltration and inflammation with subsequent fibrosis and calcification. Symptoms due to severe AS, such as exercise intolerance, exertional dyspnea, and syncope, are associated with a 1-year mortality rate of up to 50% without aortic valve replacement. Echocardiography can detect AS and measure the severity of aortic valve dysfunction. Although progression rates vary, once aortic velocity is higher than 2 m/s, progression to severe AS occurs typically within 10 years. Severe AS is defined by an aortic velocity 4 m/s or higher, a mean gradient 40 mm Hg or higher, or a valve area less than or equal to 1.0 cm2. Management of mild to moderate AS and asymptomatic severe AS consists of patient education about the typical progression of disease; clinical and echocardiographic surveillance at intervals of 3 to 5 years for mild AS, 1 to 2 years for moderate AS, and 6 to 12 months for severe AS; and treatment of hypertension, hyperlipidemia, and cigarette smoking as indicated. When a patient with severe AS develops symptoms, surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) is recommended, which restores an average life expectancy; in patients aged older than 70 years with a low surgical risk, 10-year all-cause mortality was 62.7% with TAVI and 64.0% with SAVR. TAVI is associated with decreased length of hospitalization, more rapid return to normal activities, and less pain compared with SAVR. However, evidence supporting TAVI for patients aged younger than 65 years and long-term outcomes of TAVI are less well defined than for SAVR. For patients with symptomatic severe AS, the 2020 American College of Cardiology/American Heart Association guideline recommends SAVR for individuals aged 65 years and younger, SAVR or TAVI for those aged 66 to 79 years, and TAVI for individuals aged 80 years and older or those with an estimated surgical mortality of 8% or higher. Calcific AS is a common chronic progressive condition among older adults and is diagnosed via echocardiography. Symptomatic patients with severe AS have a mortality rate of up to 50% after 1 year, but treatment with SAVR or TAVI reduces mortality to that of age-matched control patients. The type and timing of valve replacement should be built on evidence-based guidelines, shared decision-making, and involvement of a multidisciplinary heart valve team.

Timing of coronary angiography in high-risk non-ST-elevation acute coronary syndrome: results from the Portuguese Registry for Acute Coronary Syndromes (ProACS).

Current guidelines recommend an early invasive coronary angiography (ICA) within 24 h of admission for high-risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Nevertheless, meta-analyses failed to demonstrate a clear advantage of this strategy in reducing hard endpoints such as death or nonfatal myocardial infarction compared to a delayed approach. Thus, the optimal timing of ICA in high-risk NSTE-ACS remains undetermined. This study aimed to determine the optimal timing for ICA in high-risk NSTE-ACS, regarding 1-year all-cause mortality and cardiovascular rehospitalizations. We conducted a national multicenter retrospective study of high-risk NSTE-ACS patients included in the Portuguese Registry for Acute Coronary Syndromes. Patients were divided into three groups according to the time of ICA: within the first 24 h, between 24 and 48 h, and between 48 and 72 h. The incidence of in-hospital complications and mortality, 1-year mortality, and cardiovascular rehospitalizations were assessed. Of the 9949 patients included, 46.7% underwent early ICA. This was associated with a lower incidence of acute heart failure (8.5% vs. 11.1% vs. 11.5%, P < 0.001) and shorter length of stay (3 vs. 4 vs. 6 days, P = 0.012). It, however, did not reduce in-hospital complications or mortality (1.2 vs. 0.7 vs. 0.8%, P = 0.066). We also found no significant association with the composite endpoint of 1-year mortality or cardiovascular rehospitalization (15.1 vs. 15.9 vs. 15.7%, P = 0.887). Early ICA was associated with a lower incidence of acute heart failure and shorter length of stay, without a significant impact on 1-year mortality risk or cardiovascular rehospitalizations.

Lymph Node Yield and Long-Term Mortality Risk in Patients with Colon Cancer: A 20-Year Follow-Up National Study.

Lymph node status is a well-established prognostic factor for colon cancer, but the optimal number of nodes for accurate staging remains unclear. This study explored the relationship between lymph node yield (LNY) and 5-year mortality rates in colon cancer patients in New Zealand. Data from the New Zealand Cancer Registry were retrospectively analyzed for patients with TNM stage I, II, and III colon cancer between August 2003 and December 2021, with follow-up until January 2024. The primary outcome was the 5-year all-cause mortality rate, with LNY, age, sex, ethnicity, tumor site, district health board (DHB), and the number of positive nodes as covariates. Statistical analyses included univariate analysis, Cox regression modeling, and chi-squared tests. LNY was a significant predictor of 5-year mortality risk (hazard ratio 0.985, p < 0.0001), adjusted for age, sex, ethnicity, tumor site, and DHB. The strongest association between LNY and mortality rate was observed at 12 nodes. Further increases in LNY beyond 22 nodes did not lead to statistically significant differences in mortality rates. Lymph node ratio (LNR) was strongly associated with survival in stage III colon cancer, independent of LNY and the number of positive nodes. Higher LNY is significantly associated with reduced 5-year mortality rates in stage I-III colon cancer up to the 22-node mark. The strong correlation between LNR and mortality highlights its potential value for improving treatment planning in future clinical practice.

Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records.

Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised. In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital. We excluded individuals with less than 1 year of medical history records in primary or secondary care; admissions to NHS hospitals for which less than 10% of heart failure cases were linkable to the National Heart Failure Audit (NHFA); individuals younger than 18 years at the time of the heart failure hospitalisation; and patients who died in hospital during the index heart failure admission. For patients with new onset heart failure, we assessed incidence rates of 30-day and 1-year all-cause and cause-specific (cardiovascular, non-cardiovascular, and heart failure-related) emergency rehospitalisation and mortality after discharge, and dispensed guideline-recommended medical therapy (GRMT). Follow-up occurred from the index admission to the earliest occurrence of the event of interest, death, or end of data coverage. We estimated adjusted hazard ratios (HRs) to compare HFrEF with HFpEF. We computed population-attributable fractions to quantify the percentage of outcomes attributable to coexisting chronic medical conditions. Among 233 320 patients identified who survived the index heart failure admission across 335 NHS hospitals between Jan 1, 2019, and Dec 31, 2022, 101 320 (43·4%) had HFrEF, 71 910 (30·8%) had HFpEF, and 60 090 (25·8%) had an unknown classification. In patients with new onset heart failure, there were reductions in all-cause 30-day (-5·2% [95% CI -7·7 to -2·6] in 2019-22) and 1-year rehospitalisation rates (-3·9% [-6·6 to -1·2]). Declining 30-day rehospitalisation rates affected patients with HFpEF (-4·8% [-9·2 to -0·2]) and HFrEF (-6·2% [-10·5 to -1·6]), although 1-year rates were not statistically significant for patients with HFpEF (-2·2% [-6·6 to 2·3] vs -5·7% [-10·6 to -0·5] for HFrEF). There were no temporal trends in incidence rates of 30-day or 1-year mortality after discharge. The rates of all-cause (HR 1·20 [1·18-1·22]) and cause-specific rehospitalisation were uniformly higher in those with HFpEF than those with HFrEF. Patients with HFpEF also had higher rates of 1-year all-cause mortality after discharge (HR 1·07 [1·05-1·09]), driven by excess risk of non-cardiovascular death (HR 1·25 [1·21-1·29]). Rates of rehospitalisation and mortality were highest in patients with coexisting chronic kidney disease, chronic obstructive pulmonary disease, dementia, and liver disease. Chronic kidney disease contributed to 6·5% (5·6-7·4) of rehospitalisations within 1 year for HFrEF and 5·0% (4·1-5·9) of rehospitalisations for HFpEF, double that of any other coexisting condition. There was swift implementation of newer GRMT, but markedly lower dispensing of these medications in patients with coexisting chronic kidney disease. Rates of rehospitalisation in patients with heart failure in England have decreased during 2019-22. Further population health improvements could be reached through enhanced implementation of GRMT, particularly in patients with coexisting chronic kidney disease, who, despite being at high risk, remain undertreated. Wellcome Trust, Health Data Research UK, British Heart Foundation Data Science Centre.

Systemic immune-inflammation index and 2-year all-cause mortality in elderly patients with hip fracture

PurposeTo assess the association between systemic immune-inflammation index (SII) and 2-year all-cause mortality in elderly patients with hip fractures. MethodsWe performed a cohort study of hip fracture patients aged 65 years or older who received hip fracture surgery at a tertiary hospital from January 2005 to March 2022. The SII was calculated as: SII = (neutrophil count * platelet count) / lymphocyte count, based on the latest blood test before discharge. Patients were categorized into 3 groups according to SII tertiles: low SII group (≤770.92 × 109/L), medium SII group (770.92 × 109/L -1293.03 × 109/L), and high SII group (>1293.03 × 109/L). The primary outcome was 2-year all-cause mortality. We evaluated the association between SII and 2-year all-cause mortality using the multivariate Cox regression model. ResultsAmong 2,766 patients, 296 patients died during the 2-year follow-up period. The incidence of 2-year all-cause mortality per 1,000 persons was 90.0 (95% CI, 73.2-110.2) in the low SII group, 86.8 (95% CI, 70.3-106.7) in the medium SII group, and 144.3 (95% CI, 123.1-168.5) in the high SII group. Compared with patients in the low SII group, the hazard ratio for 2-year all-cause mortality was 0.97 (95% Cl 0.69-1.37) in the medium SII group and 1.47 (95% Cl 1.07-2.01) in the high SII group (P for trend, 0.001). ConclusionSII is significantly associated with 2-year all-cause mortality in elderly patients with hip fracture. SII may be used to identify patients at high risk of mortality after hip fracture surgery.

Association of Psychotropic Prescriptions With Non-Registered Indications and the Risk of Mortality in Older Adults: A Danish Nationwide Cohort Study.

Psychotropic drug use is common in older adults, with off-label use reported despite limited understanding of the safety outcomes compared to on-label use. Incomplete recordings of treatment indications in the Danish National Prescription Register (DNPR) raise concerns about potential off-label medication use, particularly among older adults. We, therefore, investigated the association between psychotropic prescriptions with non-registered indications in DNPR and the 1-year all-cause mortality in older adults, including subgroups with any psychiatric disorders, depression, or dementia. Register-based cohort study following all older adults (≥ 65) who redeemed a first-time (since 1995) prescription of either antidepressants, antipsychotics, or benzodiazepine during 2006-2017. Redemption of a prescription with non-registered indications in the DNPR was the exposure. The outcome, 1-year all-cause mortality was analyzed using Poisson regression, estimating incidence rate ratios with 95% confidence intervals, adjusting for socio-demographics and clinical factors. 32% of prescriptions filled by 202,067 individuals for antidepressants, 37% of 97,387 for antipsychotics, and 22% of 130,471 for benzodiazepines had non-registered indications. No significant differences in mortality rates were found for antidepressants and antipsychotics with non-registered indications, while higher mortality rates were associated with benzodiazepines, mitigated when excluding individuals receiving intravenous administrations representing end-of-life treatment. The results remained consistent in subgroup analyses in patients with any psychiatric disorders, depression, or dementia and further stratified analyses by sex and age. We found that while psychotropic prescriptions with non-registered indications in DNPR were prevalent in older adults, they were not associated with excess mortality.

Characteristics and Outcomes of Patients With Valvular Cardiogenic Shock

BackgroundThe clinical characteristics and outcomes of patients who develop cardiogenic shock (CS) secondary to primary valvular dysfunction (valvular cardiogenic shock [VCS]) remain unclear. ObjectivesThe purpose of this study was to describe the cohort of patients with VCS and understand their outcomes compared to other forms of CS. MethodsAll patients admitted to Cleveland Clinic cardiac intensive care unit between January 1, 2010, and December 31, 2021, with a diagnosis of CS were retrospectively identified. Characteristics and outcomes for shock patients with VCS were compared to those without VCS. ResultsA total of 2,754 patients were admitted to our cardiac intensive care unit with CS, of which 442 (16%) had VCS. The median age of patients with VCS was higher than those with non-VCS (70 years vs 64 years, P < 0.001) and were more likely females (40.3% vs 32.1%, P = 0.001). VCS was predominantly due to native valve dysfunction as compared to prosthetic valve dysfunction (71% vs 29%, P < 0.001), with the aortic valve noted to be the most common valve affected. Patients with VCS had higher 1-year (44% vs 37%, P < 0.001) and 30-day all-cause mortality (28% vs 20%, P < 0.001) compared to those without VCS. When compared to percutaneous intervention and medical therapy alone, surgical intervention in VCS was associated with the best short- and long-term outcomes (P < 0.001). ConclusionsVCS is associated with poor short and long outcomes. Native valvular dysfunction and aortic valve involvement account for the majority of patients with VCS. Definitive surgical therapy and expanding the role of percutaneous therapies may be pivotal in improving clinical outcomes in this high-risk cohort.

Impact Of Preoperative Risk Factors On 5-year Survival After Fenestrated/Branched Endovascular Aortic Repair

To investigate which preoperative factors most impact the 5-year survival of patients undergoing fenestrated/branched endovascular aortic repair (F/BEVAR) and to identify modifiable elements that, if time allows, should be actively managed and adequately controlled preoperatively. Patients treated for aortic aneurysms with complex anatomy using either a patient-specific company manufactured or an off-the-shelf F/BEVAR devices were included. The exposure of interest was aneurysm type (group I: types I-III thoracoabdominal aneurysms (TAAA) vs group II: type IV TAAA vs group III: juxtarenal or suprarenal aneurysms) and the primary outcome was 5-year risk of all-cause mortality. Generalized linear models were used to estimate each group's crude 5-year risk of death and the 5-year risk of death across groups. Each preoperative factor was added to the model individually and a change in estimate was calculated between the new risks and the crude risk. Preoperative factors with a change of estimate of ≥10% were utilized to create an inverse probability of treatment weights for multivariable analysis. Results: 408 F/BEVAR patients were included, who were 71.6% male (mean age: 72.0±7.9 years). Eleven of the 22 preoperative factors analyzed had a change in estimate ≥10%. The greatest changes in estimates were observed for history of congestive heart failure (CHF), arrhythmia, overweight, obesity, COPD. Almost 60% of patients with CHF in group I died within 5 years. Current smoking or overweight at the time of F/BEVAR increases the 5-year risk of death more significantly than having a history of myocardial infarction. After adjustment, patients in group I had a significantly higher risk of 5-year all-cause mortality compared to those in group III (log-rank p-value=0.0082). The present findings suggest that cardiac arrhythmias, CHF, overweight, obesity, COPD, and aneurysm diameter above 7 cm are the most relevant preoperative elements that impact the 5-year survival post F/BEVAR. More specifically, CHF and arrhythmias should be used to alter patient selection and identify those individuals more likely to benefit from repair. Moreover, modifiable risk factors such as weight loss and smoking cessation during the surveillance period before the F/BEVAR procedure, might improve survival in this population. Considering that preoperatively, many patients are periodically evaluated by a vascular surgery team until the aneurysm diameter meets criteria for repair, a multidisciplinary approach that could address these modifiable risk factors might be an impactful strategy.

Validation of the Valve Academic Research Consortium High Bleeding Risk Definition in Patients Undergoing TAVR.

Background: The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) has recently introduced a consensus document that outlines risk factors to identify high bleeding risk (HBR) in patients undergoing transcatheter aortic valve replacement (TAVR). The objective of the present study was to evaluate the prevalence and predictive value of the VARC-HBR definition in a contemporary, large-scale TAVR population. Methods: Multicenter study including 10,449 patients undergoing TAVR. Based on consensus, twenty-one clinical and laboratory criteria were identified and classified as major or minor. Patients were stratified as at low, moderate, high, and very high bleeding risk according to VARC-HBR definition. The primary endpoint was the rate of BARC type 3 or 5 bleeding at 1 year, defined as the composite of peri-procedural (within 30 days) or late (after 30 days) bleeding. Results: Patients with at least one VARC-HBR criterion (n=9,267, 88.7%) had a higher risk of BARC 3 or 5 bleeding, proportional to the severity of risk assessment (10.8%, 16.1%, and 24.6% for moderate, high, and very high-risk groups, respectively). However, a comparable rate of bleeding events was observed in the low-risk and moderate-risk groups. The area under ROC curve was 0.58. Patients with VARC-HBR criteria also exhibited a gradual increase in 1-year all-cause mortality, with an up to 2-fold increased mortality risk for high and very high-risk groups (HR: 1.33, 95% CI: 1.04-1.70; and HR: 1.97, 95% CI: 1.53-2.53, respectively). Conclusions: The VARC-HBR consensus offered a pragmatic approach to guide bleeding risk stratification in TAVR. The results of the present study would support the predictive validity of the newly definition and promote its application in clinical practice to minimize bleeding risk and improve patient outcomes.

Relationship between clinical congestion and worsening renal function after intravenous initiation of furosemide in patients with acute heart failure.

To investigate if worsening renal function (WRF) appearing in some patients with acute heart failure (AHF) after intravenous furosemide initiation is influenced by severity of congestion. We conducted a retrospective secondary analysis of consecutive patients diagnosed with AHF and prospectively included in 10 Spanish emergency departments (EDs) for whom serum creatinine at ED arrival and after 2-7days of intravenous furosemide initiation were available. Congestion was clinically evaluated by identification of 7 signs/symptoms and by chest X-ray. The outcome was WRF, defined as a delta-creatinine ≥ 0.3mg/dL. Risk of WRF according to congestion was estimated in models adjusted by patient baseline characteristics and vitals at ED arrival, and interaction was also investigated. We included 3027 patients (median age 82years, 56% women), and 657 (21.7%) presented WRF after intravenous furosemide initiation. When signs/symptoms were individually considered, only lower limbs edema was associated with decreased risk of WRF (20.1% vs. 24.8%; OR = 0.76, 95%CI = 0.64-0.91). After adjustment, lower limbs edema persisted inversely associated with WRF (aOR = 0.78, 95%CI = 0.65-0.94), with significant lower risk for patients ≤ 80years and without chronic kidney disease, functional limitation, and hypoxemia (p for interaction 0.01, 0.04, 0.02 and 0.03, respectively). Neither degree of clinical congestion (number of signs/symptoms of congestion) nor radiological congestion in chest X-ray were related to WRF. Worsening renal function was associated with a higher 1-year all-cause mortality (40.1% vs 34.6%; HR = 1.27, 1.10-1.46; aHR = 1.331, 1.151-1.540). In patients with WRF, liver cirrhosis, chronic treatment with loop diuretics and renin-angiotensin system inhibitors, age (> 80years), dementia, heart valve disease and NYHA class III-IV were associated with higher mortality. Intravenous furosemide initiation in patients with AHF without lower limbs edema must be cautious, as they are at increasing risk of developing WRF during the next following days, which in turn is associated with a higher 1-year mortality.

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p &amp;lt; 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p &amp;lt; 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p &amp;lt; 0.001 and HR 1.12, p &amp;lt; 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p &amp;lt; 0.001 and HR 6.99, p &amp;lt; 0.001), cardiogenic shock (HR 26.3, p &amp;lt; 0.001, HR 12.0, p &amp;lt; 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p &amp;lt; 0.001, HR 18.1, p &amp;lt; 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p &amp;lt; 0.001) and (HR 62.7, p &amp;lt; 0.007; HR 18.9, p &amp;lt; 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

Growth differentiation factor-15 and 5-years cardiovascular risk in chest pain patients presenting to the emergency department: a multicenter cohort study

Abstract Background Growth differentiation factor 15 (GDF-15) has been explored as a prognostic biomarker in multiple disease entities, including ischemic heart disease and heart failure (HF), but its role as a prognostic marker in chest pain patients presenting to the emergency department (ED) is unknown. Purpose To investigate the association between GDF-15 and 5-year all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE), and to evaluate its prognostic incremental value. Methods Patients presenting to the ED with acute chest pain were prospectively enrolled in an international multicenter diagnostic study. GDF-15 concentrations were measured in a blinded fashion upon ED presentation. Follow-ups were performed at 3 months, 1-, 2- and 5-years. MACE was defined as the composite of cardiovascular mortality, acute myocardial infarction, stroke, and HF rehospitalization. Associations between GDF-15 and each prognostic outcome were modeled using multivariable Cox proportional hazard regression fitting restricted cubic splines to continuous variables. The magnitude of the effect of each GDF-15 unit change on multivariable-adjusted models was assessed graphically using dose-response plots. To compute an HR for the dose-response plots we chose a GDF-15 value of 1200 pg/mL as a reference value as this has been chosen in previous literature1. For the restricted cubic splines three knots were used. The added prognostic value of GDF-15 was evaluated by the increase in the C-statistic between a base and an extended model and the fraction of new information (FNI) provided by GDF-15. Results A total of 4779 chest pain patients had baseline GDF-15 values available. The median age was 61 [48-74] and 33% were female. Higher GDF-15 levels were more strongly associated with heart failure, kidney dysfunction, older age, hypertension, diabetes and coronary artery disease. GDF-15 was independently associated with 5-years all-cause mortality, cardiovascular mortality and MACE (Figure). When adding GDF-15 to a rich-for-prior-information base model which included age, sex, cardiovascular risk factors, creatinine, cardiac troponin and NT-proBNP, GDF-15 provided relevant incremental prognostic discrimination for 5-years all-cause death and cardiovascular death. (Table). Conclusions In chest pain patients presenting to the emergency department, GDF-15 concentration on admission was associated with 5-years all-cause mortality, cardiovascular mortality, and MACE. In addition, it provided relevant incremental prognostic information when added on top of troponin and NT-proBNP, the two current prognostic gold standard biomarkers.FigureTable

A propensity score matched analysis of transcatheter aortic valve replacement in failed bioprosthetic valves

Abstract Introduction While recently published data indicate similar long-term results of transcatheter aortic valve replacement (TAVR) compared to surgical procedures, surgical aortic valve replacement (SAVR) remains the standard of care in low-risk patients. However, since life expectancy increases, a non-negligible number of patients experience bioprosthetic valve dysfunction with the need for reintervention, but long-term data of TAVR in failed bioprosthetic valves is scarce. Purpose The aim of the study was to analyse long-term data of patients with TAVR in failed bioprosthetic valves compared to patients with native valve TAVR. The primary endpoint was 6-year all-cause mortality and the main secondary endpoint was echocardiographic valve function. Methods Patients undergoing TAVR for severe aortic valve disease between December 2012 and December 2020 were retrospectively analysed. Prior TAVR or aortic valve homografts led to exclusion from the study. A 2:1 propensity score matching by the optimal neighbor matching algorithm was performed to overcome differences in baseline characteristics. Results Between December 2012 and December 2020, 3,423 patients received TAVR for severe aortic valve disease and met inclusion criteria for the study. Of those, 3,287 patients underwent native valve TAVR, whereas 136 patients experienced bioprosthetic valve dysfunction and were treated with TAVR-in-SAV. After 2:1 propensity score matching, baseline characteristics without any relation to prior SAVR were similar between both groups. Concerning postprocedural echocardiographic function, a less pronounced gradient reduction (57.0 vs. 71.0 %, p &amp;lt; 0.01, Figure 1) and a higher number of patients with elevated mean pressure gradient &amp;gt; 20 mmHg could be found after prior SAVR (19.4 vs. 3.0 %, p &amp;lt; 0.01). However, there was no difference regarding 6-year all-cause mortality between both groups (log rank test p = 0.8, Figure 2). Conclusions Besides a less pronounced gradient reduction and higher mean aortic pressure gradients after TAVR-in-SAV compared to patients with native valve TAVR, no differences in 6-year all-cause mortality could be observed in a propensity score matched analysis.Reduction of mean pressure gradient6-year all-cause mortality

Prognostic significance of type 4a myocardial infarction and periprocedural myocardial injury in NSTEMI patients

Abstract Background Type 4a myocardial infarction (MI) and periprocedural myocardial injury (PMI) might occur in patients with non-ST-elevation MI (NSTEMI) after percutaneous coronary intervention (PCI) procedures. Purpose This study investigated the incidence and prognostic relevance of type 4a MI and PMI, according to current definitions, in NSTEMI patients undergoing PCI. The best cardiac troponin (cTn) threshold of PMI for prognostic stratification is also identified. Methods In this observational cohort study, we enrolled consecutive NSTEMI patients undergoing PCI with stable or falling pre-PCI cTn levels. According to the 4th Universal Definition of Myocardial Infarction (UDMI), we stratified the study population into three subgroups: those experiencing 1) type 4a MI; 2) PMI; 3) no periprocedural ischemic events. The primary endpoint was 1-year all-cause mortality. The secondary endpoint consisted in a composite of major adverse cardiovascular events (MACE) at 1-year, including all-cause mortality, non-fatal reinfarction, urgent revascularization, non-fatal ischemic stroke and hospitalization for heart failure. Results Among 1412 NSTEMI patients undergoing PCI with stable or falling cTn levels at baseline, 240 (17.0%) experienced type 4a MI, 288 (20.4%) PMI, and 884 (62.6%) no periprocedural ischemic events. Patients with type 4a MI had the highest 1-year all-cause mortality and MACE rates. PMI defined by the 4th UDMI (post-PCI delta cTn &amp;gt;20%) did not show significant associations with primary and secondary endpoints. PMI redefined as post-PCI delta cTn &amp;gt;40% was significantly correlated with 1-year all-cause mortality and MACE. Conclusion Periprocedural ischemic events are common in NSTEMI patients undergoing PCI and influence patient outcomes. Type 4a MI and PMI redefined as post-PCI delta cTn &amp;gt;40% are strongly associated with 1-year death and MACE. This study highlights the importance of identifying periprocedural ischemic events to aid risk stratification and management of NSTEMI patients.PMI and type 4a MI: mortality 1-yearPMI and type 4a MI: MACE 1-year

Transcatheter aortic valve replacement with balloon-expandable and self-expandable valves in Japanese patients with large annulus: the OCEAN-TAVI registry

Abstract Background East Asians have smaller aortic valve complexes than individuals from Western countries, and few studies have reported transcatheter aortic valve replacement (TAVR) outcomes in Asian patients with a large annulus. Purpose We aimed to compare the acute and long-term outcomes of TAVR using balloon-expandable valves (BEVs) and self-expandable valves (SEVs) in Asian patients with a large annulus. Methods We retrospectively analyzed the data from the Optimized transCathEter vAlvular interveNtion Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. A large annulus was defined by annular area ≥ 500 mm2 and average diameter ≥ 25 mm in computed tomography scans. The primary endpoint was the 3-year all-cause mortality. Secondary endpoints were 3-year heart-failure rehospitalization (HFR) after TAVR, acute outcomes of TAVR, and changes in valve function on echocardiography 2 years after TAVR. Results Among 773 patients, 671 (86.8%) underwent BEV-TAVR. The SEV-TAVR group showed a significantly higher incidence of above-moderate perivalvular leakage (2.1% vs. 7.8%; P &amp;lt; 0.001), and included a significantly greater percentage of patients who required postoperative pacemaker implantation (6.1% vs. 11.8%; P = 0.035). The incidence of moderate-to-severe prosthesis–patient mismatch did not differ between the two groups. The Kaplan–Meier curve showed no significant intergroup differences in the 3-year all-cause mortality and HFR rates (log-rank P = 0.900), and the echocardiography-indexed effective orifice area and mean transaortic valve pressure gradient at 2 years post-TAVR did not differ significantly between the two groups. Conclusions The benefits of BEV-TAVR may outweigh those of SEV-TAVR in patients with a large annulus.

Sex-specific models to predict 5-year mortality after ST-elevation myocardial infarction using machine learning: insight from FAST-MI registry

Abstract Background Most prognostic stratification tools in acute myocardial infarction (AMI) have been derived from populations including both women and men and including only a small proportion of women. Purpose Using supervised machine learning (ML), we examined the performance of 2 models assessing 5-year mortality after AMI, one derived from a population of women only and one from a population of men only, to determine whether sex-specific models improved outcome prediction. Methods This cohort study used the French registry on acute ST-elevation and non-ST-elevation myocardial infarction (FAST-MI) 2010 and 2015 surveys. This multicentric registry led in more than 200 French hospitals, enrolled all consecutive patients with acute myocardial infarction during a 1-month recruitment period. Our analysis included all men and women presenting STEMI who underwent invasive coronary angiography (ICA). To build and validate the models, the data set were split with a 70%/30% ratio into training and testing sets. The primary outcome was 5-year all-cause mortality. Then, 52 clinical, laboratory, ECG, echocardiographic, and ICA parameters were evaluated for feature selection using Boruta algorithm. Different supervised machine learning algorithms, including random forest (RF), were assessed for model building, and their performance were compared in women and men. To compare prediction accuracy according to sex, we evaluate the performance of the women-based ML model in men from the same cohort. Results 1,189 consecutive women and 3,685 men with STEMI (mean age 61±13 and 69±15 years, respectively) were recruited; 12% of men and 20% of women experienced 5-year all-cause mortality. Using Boruta algorithm, the 10 most important variables for prediction were selected (Figure 1). For women-based ML model building, the RF algorithm exhibited the best performance to predict mortality with an area under the receiver-operating characteristic curve (ROC-AUC) of 0.82 (95% CI: 0.77 – 0.88), an area under the precision-recall curve (PR-AUC) of 0.59 (95% CI: 0.54 – 0.64); and a F1-score of 0.58. The women-based ML model exhibited lower performance in men (ROC-AUC: 0.78; PR-AUC: 0.43; Figure 2). Conversely, the men-based model exhibited better accuracy in men than in women. Conclusion In a large multicentric cohort of STEMI patients, a women-based ML-model exhibited a good accuracy to predict 5-year all-cause mortality in women, but a drop of accuracy when applied to men. In mirror, the accuracy of the men-based model was lower in women. This suggests that sex-specific models might be superior to general models to predict mortality after AMI.Features selection and ML model buildingML model performance according to sex