Risk Of Adverse Clinical Events Research Articles

Initial eGFR Changes with SGLT2 Inhibitor in Patients With Type 2 Diabetes and Associations With the Risk of Abnormal Serum Potassium Level.

Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow-up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of -3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28-9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78-3.95]) as well as hypokalemia events <3.0 mmol/L (adjusted hazard ratio, 3.21 [95% CI, 1.90-5.42]) or use of potassium supplement (adjusted hazard ratio, 1.87 [95% CI, 1.37-2.56]) following SGLT2i treatment after multivariate adjustment. Physicians should be aware that the eGFR trough occurs shortly, and consequent serum potassium changes following SGLT2i initiation.

Prognostic implications of pre-transcatheter aortic valve replacement computed tomography-derived coronary plaque characteristics and stenosis severity.

The study aimed to investigate the prognostic value of pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) in assessing physiological stenosis severity (CTA-derived fractional flow reserve (CT-FFR)) and high-risk plaque characteristics (HRPC). Among TAVR patients who underwent pre-procedure CTA, the presence and number of HRPCs (minimum lumen area of < 4 mm2, plaque burden ≥ 70%, low-attenuating plaques, positive remodeling, napkin-ring sign, or spotty calcification) as well as CT-FFR were assessed. The risk of vessel-oriented composite outcome (VOCO, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) was compared according to the number of HRPC and CT-FFR categories. Four hundred and twenty-seven patients (68.4% were male) with 1072 vessels were included. Their mean age was 70.6 ± 10.6years. Vessels with low CT-FFR (≤ 0.80) (41.7% vs. 15.8%, adjusted hazard ratio (HRadj) 1.96; 95% confidence interval (CI): 1.28-2.96; p = 0.001) or lesions with ≥ 3 HRPC (38.7% vs. 16.0%, HRadj 1.81; 95%CI 1.20-2.71; p = 0.005) demonstrated higher VOCO risk. In the CT-FFR (> 0.80) group, lesions with ≥ 3 HRPC showed a significantly higher risk of VOCO than those with < 3 HRPC (34.7% vs. 13.0%; HRadj 2.04; 95%CI 1.18-3.52; p = 0.011). However, this relative increase in risk was not observed in vessels with positive CT-FFR (≤ 0.80). In TAVR candidates, both CT-FFR and the presence of ≥ 3 HRPC were associated with an increased risk of adverse clinical events. However, the value of HRPC differed with the CT-FFR category, with more incremental predictability among vessels with negative CT-FFR but not among vessels with positive CT-FFR. In transcatheter aortic valve replacement (TAVR) candidates, pre-TAVR CTA provided the opportunity to assess coronary physiological stenosis severity and high-risk plaque characteristics, both of which are associated with worse clinical outcomes. • The current study investigated the prognostic value of coronary physiology significance and plaque characteristics in transcatheter aortic valve replacement patients. • The combination of coronary plaque vulnerability and physiological significance showed improved accuracy in predicting clinical outcomes in transcatheter aortic valve replacement patients. • Pre-transcatheter aortic valve replacement CT can be a one-stop-shop tool for coronary assessments in clinical practice.

Pressure overload is associated with right ventricular dyssynchrony in heart failure with reduced ejection fraction.

The determinants and relevance of right ventricular (RV) mechanical dyssynchrony in heart failure with reduced ejection fraction (HFrEF) are poorly understood. We hypothesized that increased afterload may adversely affect the synchrony of RV contraction. A total of 148 patients with HFrEF and 36 controls underwent echocardiography, right heart catheterization, and gated single-photon emission computed tomography to measure RV chamber volumes and mechanical dyssynchrony (phase standard deviation of systolic displacement timing). Exams were repeated after preload (N=135) and afterload (N=15) modulation. Patients with HFrEF showed higher RV dyssynchrony compared with controls (40.6±17.5° vs. 27.8±9.1°, P<0.001). The magnitude of RV dyssynchrony in HFrEF correlated with larger RV and left ventricular (LV) volumes, lower RV ejection fraction (RVEF) and LV ejection fraction, reduced intrinsic contractility, increased heart rate, higher pulmonary artery (PA) load, and impaired RV-PA coupling (all P≤0.01). Low RVEF was the strongest predictor of RV dyssynchrony. Left bundle branch block (BBB) was associated with greater RV dyssynchrony than right BBB, regardless of QRS duration. RV afterload reduction by sildenafil improved RV dyssynchrony (P=0.004), whereas preload change with passive leg raise had modest effect. Patients in the highest tertiles of RV dyssynchrony had an increased risk of adverse clinical events compared with those in the lower tertile [T2/T3 vs. T1: hazard ratio 1.98 (95% confidence interval 1.20-3.24), P=0.007]. RV dyssynchrony is associated with RV remodelling, dysfunction, adverse haemodynamics, and greater risk for adverse clinical events. RV dyssynchrony is mitigated by acute RV afterload reduction and could be a potential therapeutic target to improve RV performance in HFrEF.

The significance of dynamic monitoring plasma TMAO level in pulmonary arterial hypertension - a cohort study.

Gut microbiota assumes an essential role in the development and progression of pulmonary arterial hypertension (PAH). Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, is correlated with the prognosis of patients with PAH. However, the correlation between changes in TMAO (ΔTMAO) and the prognosis of PAH remains elusive. To investigate the association between ΔTMAO and prognosis of PAH, and explore whether dynamic assessment of TMAO level was superior to measurement at a single time point in predicting prognosis. Single-center cohort study. Consecutive patients diagnosed with PAH and had at least two TMAO measurements taken from May 2019 to June 2020 were eligible. The outcome events of this study were defined as adverse clinical events. A total of 117 patients with PAH who had two TMAO measurements and follow-up were included in this study. Patients with ΔTMAO ⩾1.082 μmol/L had over four times increased risk of adverse clinical events than their counterparts after adjusting for confounders [hazard ratio (HR) 4.050, 95% confidence interval (CI): 1.468-11.174; p = 0.007]. Patients with constant high TMAO levels at both time points had the highest risk of adverse clinical events compared with patients with constant low TMAO levels (HR 3.717, 95% CI: 1.627-8.492; p = 0.002). ΔTMAO was also associated with changes in parameters reflecting PAH severity (p < 0.05). Changes in TMAO were independently correlated with prognosis in patients with PAH, irrespective of baseline level of TMAO. ΔTMAO also correlated with alteration in disease severity. Repeated assessment of TMAO level contributes to better identification of patients with increased risk of adverse clinical events.

Clinical analysis of patients with hemodynamic depression after carotid artery stenting

Hemodynamic depression (HD) is a complication after carotid artery stenting (CAS). However, there are existing controversies in predicting postoperative risk factors and subsequent clinical outcomes, especially in high-risk patients. Therefore, the present study aimed to investigate the rate of incidence, clinical predictors, and clinical significance associated with persistent HD (p-HD) pathology, as well as obstinate persistent HD (op-HD) after CAS in our center. We retrospectively analyzed 162 consecutively recruited carotid arteriosclerotic stenosis (CASS) patients who received interventional therapy in our hospital between September 2020 and September 2022. The acute/subacute effects of proximal internal CAS on p-HD and op-HD were studied to explore the relationship between CAS and perioperative adverse events. Logistic regression analysis was performed to identify independent predictors of p-HD after CAS. Pathological associations between p-HD/op-HD and clinical events at the 30-day time point were analyzed. Of 162 patients, 18.5 % (n = 30) patients had p-HD, while op-HD was observed in 5.6 % (n = 9) of patients. Hypertension (OR: 8.73; 95 % CI: 1.05–72.90; P = 0.045), history of stroke/transient ischemic attack (TIA) (OR: 4.05; 95 % CI: 1.55–10.59; P = 0.004), coronary artery disease (CAD) (OR: 3.38; 95 % CI: 1.29–8.89; P = 0.013), and distance from the carotid bifurcation to the lesion with maximum stenosis (OR: 2.467; 95 % CI: 1.02–5.93; P = 0.044) were significantly associated with p-HD onset. Patients with either p-HD or op-HD suffered from longer intensive care unit (ICU) stays (all P < 0.001) and were associated with a higher risk of stroke (P = 0.003; P < 0.001). Our data suggest that hypertension, previous stroke/TIA, CAD, and distance from the carotid bifurcation to the lesion with maximum stenosis may play roles in the development of p-HD after CAS. Moreover, this study indicates that either p-HD/op-HD can be associated with the risk of clinical adverse events, especially stroke.

Neighborhood Disadvantage Increases Risk of Adverse Clinical Events in Children with Sickle Cell Disease

Background: Hydroxyurea is the most widely used pharmacologic agent to treat patients with sickle cell disease (SCD). Hydroxyurea treatment has well established effects of inducing expression of fetal hemoglobin (HbF) and a beneficial impact on clinical outcomes such as reduced number of vaso-occlusive (VOC) events, transfusions, and hospitalizations. In non-SCD populations, living in socio-economic disadvantage is a well-established factor for poor health outcomes. However, there is a paucity of data to describe how social stressors impact children with SCD. We hypothesized that socio-economic disadvantage impacts risk of adverse clinical outcomes in pediatric SCD patients even while on hydroxyurea therapy. Methods: We performed a retrospective chart review on 121 pediatric patients with severe SCD genotypes (homozygous HbS and sickle-beta 0 thalassemia) seen at Texas Children's Hospital (TCH) between 2010-2021. All patients were treated with hydroxyurea for a minimum of five years. Adherence to hydroxyurea was assessed through lab markers including absolute neutrophil count and reticulocyte counts. Patients not adherent were excluded from analysis. We examined the incidence of all clinical events for a total of 1026 patient years, including the number of office visits, ER visits, hospitalizations, transfusions, VOC, acute chest syndrome episodes (ACS), acute splenic sequestration (ASS), and febrile illness. We collected laboratory data including absolute neutrophil count, hemoglobin level, and HbF levels for each patient per year they were on hydroxyurea. We used the area deprivation index (ADI) to determine a score of neighborhood disadvantage amongst our cohort of patients. The ADI is a factor-based index which uses 17 US Census variables including poverty, education, and employment. We used individual residential addresses during our observation period to assign a geocode specific to each individual and obtain an ADI score. The ADI scores are ranked from 1-10, with higher ADI rankings reflecting a higher level of disadvantage. Results: All individuals with SCD had a robust response to hydroxyurea within their first year of initiating the drug (&amp;gt;20% HbF). We stratified our cohort based on their ADI scores into low ADI (1-3; n=42); medium ADI (4-6; n=42); and high ADI groups (7-10; n=37), where high ADI is the group with highest levels of disadvantage. All three groups had a similar average duration of hydroxyurea treatment. There were no significant differences in age, sex, or reason given for starting hydroxyurea between the ADI groups. When we examined hydroxyurea response, there was no significant difference in HbF levels at 1 year (23.8 vs. 24.06 %HbF in the low vs. high ADI groups) or after 5 years (19.6 vs. 18.6 % HbF in the low and high ADI groups). Individuals with high ADI did started hydroxyurea at a younger age (2.9 years vs. 4.9 years, p=0.02). We found that any individual living in an area with higher ADI had an increased incidence of adverse clinical events. We calculated the incidence of each clinical event per 100 patient years in our 3 ADI groups and used a conditional maximum likelihood estimate of rate ratio method to compare incidences (Table 1). We found that among individuals living in an area with a higher ADI (more deprived region), there was increased frequency of ER visits, hospitalizations, transfusions, VOC, and ASS. In particular, patients with the highest ADI had a 3 and 5 times higher rate of VOC and ASS, respectively (Table 1). Discussion: While we did not observe an association between ADI and HbF expression, our results show that higher neighborhood disadvantage is associated with poorer clinical outcomes among hydroxyurea-adherent pediatric patients with SCD who maintained a robust response to the drug (&amp;gt;20% HbF). All individuals in our study had a similar number of routine office visits at our clinic but any patient living in an area of high ADI had significantly more ER visits and hospitalizations for VOC and ASS events. While hydroxyurea is shown to reduce hospitalizations and VOC events in pediatric sickle cell patients, we show that neighborhood disadvantage can influence clinical outcomes even among patients who respond to hydroxyurea. More analysis remains in order to better characterize this association, and to understand additional strategies that can be used to reduce clinical events in pediatric patients of lower socioeconomic status.

Increased Left Ventricular End-Diastolic Volume Index Is Associated With Increased Adverse Events After MitraClip Implantation

This study investigated the association between the left ventricular end-diastolic volume index (LVEDVI) and the incidence of adverse clinical events in patients after MitraClip implantation. In this retrospective, observational study, 123 patients who underwent the MitraClip procedure were enrolled. Participants were divided into 2 groups according to the LVEDVI cut-off level, calculated using receiver operating characteristic curve analysis, to predict the primary end point and the occurrence of cardiovascular events was compared between the groups. The primary end point was all-cause mortality and hospitalization because of heart failure. The receiver operating characteristic curve analysis for the composite primary end point revealed an LVEDVI cut-off point of 118ml/m2. Based on this threshold, 61 patients (49.6%) were categorized into the LVEDVI <118 ml/m2 group, whereas 62 (50.4%) fell into the LVEDVI ≥118 ml/m2 group. Over a median follow-up period of 336days (interquartile range 80 to 667), the primary end points occurred in 15 and 26 patients in the LVEDVI <118 and LVEDVI ≥118 ml/m2 groups, corresponding to incidence rates of 24.6% and 41.9%, respectively. Patients in the LVEDVI ≥118ml/m2 group demonstrated a significantly higher risk of adverse clinical events than those in the LVEDVI <118ml/m2 group (hazard ratio 2.24, 95% confidence interval 1.17 to 4.28, p=0.01). This trend persisted even after adjusting for several confounders (p=0.02). In conclusion, increased LVEDVI values were associated with increased adverse clinical events after MitraClip implantation in patients with severe mitral valve regurgitation.

Abstract 13106: Two-Year Clinical Outcomes of Staged Transcatheter Mitral Edge-to-Edge Repair After Transcatheter Aortic Valve Replacement

Introduction: Residual significant MR has been linked to an increased risk of adverse clinical events in patients undergoing TAVR. However, the effectiveness of staged TEER after TAVR has been poorly assessed. Hypothesis: To investigate clinical outcomes of staged transcatheter edge-to-edge repair (TEER) for residual significant mitral regurgitation (MR) after transcatheter aortic valve replacement (TAVR). Methods: This observational study included consecutive patients with residual grade 3+ or 4+ MR after TAVR performed at our institution between April 2016 and November 2020. The primary composite outcomes were all-cause mortality and heart failure (HF) hospitalization at 2 years, with HF hospitalization assessed as a secondary outcome for all-cause mortality. Additional analyses, including changes in MR grade and New York Heart Association (NYHA) functional classification, were performed. Results: Among 314 patients, 104 (33.1%) treated with staged TEER and 210 (66.9%) treated with medical therapy alone were enrolled. Patients who underwent staged TEER had a lower rate of primary composite outcomes than those who received medical therapy alone (33.7% vs. 48.1%, p=0.027) (Figure1). However, there was no significant difference in all-cause mortality (11.5% vs. 13.8%, p=0.46) or HF hospitalization (31.7% vs. 42.9%, p=0.061). Staged TEER was associated with a marked improvement in the MR grade and NYHA class from baseline to 2 years. Conclusions: Staged TEER following TAVR was associated with improved clinical outcomes and a reduced MR grade. The findings suggest that TEER should be considered a potential treatment option for significant residual MR in patients who have previously undergone TAVR.

Routine stress testing in diabetic patients after percutaneous coronary intervention: the POST-PCI trial.

The optimal follow-up surveillance strategy for high-risk diabetic patients with had undergone percutaneous coronary intervention (PCI) remains unknown. The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) study was a randomized trial comparing a follow-up strategy of routine functional testing at 1 year vs. standard care alone after high-risk PCI. Randomization was stratified according to diabetes status. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Among 1706 randomized patients, participants with diabetes (n = 660, 38.7%) had more frequent comorbidities and a higher prevalence of complex anatomical or procedural characteristics than those without diabetes (n = 1046, 61.3%). Patients with diabetes had a 52% greater risk of primary composite events [hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.02-2.27; P = .039]. The 2-year incidences of the primary composite outcome were similar between strategies of routine functional testing or standard care alone in diabetic patients (7.1% vs. 7.5%; HR 0.94; 95% CI 0.53-1.66; P = .82) and non-diabetic patients (4.6% vs. 5.1%; HR 0.89; 95% CI 0.51-1.55; P = .68) (interaction term for diabetes: P = .91). The incidences of invasive coronary angiography and repeat revascularization after 1 year were higher in the routine functional-testing group than the standard-care group irrespective of diabetes status. Despite being at higher risk for adverse clinical events, patients with diabetes who had undergone high-risk PCI did not derive incremental benefit from routine surveillance stress testing compared with standard care alone during follow-up.

Discordance Between Neutrophil to Lymphocyte Ratio and High Sensitivity C-Reactive Protein to Predict Clinical Events in Patients with Stable Coronary Artery Disease: A Large-Scale Cohort Study.

Neutrophil to lymphocyte ratio (NLR), a novel inflammatory biomarker, has been shown to positively predict prognosis independent of high-sensitivity C-reactive protein (hsCRP) in patients with coronary artery disease (CAD). This study aimed to use discordance analysis to evaluate the effectiveness of NLR and hsCRP to predict adverse events in patients with stable CAD. This observational cohort study included 7827 consecutive CAD patients at Fuwai Hospital from March 2011 to April 2017. Discordant NLR with hsCRP was defined by the highest quartiles and medians. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. During a median 36-month follow-up, 624 (8.0%) MACCEs occurred. Compared with the lowest NLR quartile,a significantly higher risk of MACCEs was observed in the highest NLR quartile after adjusting for confounding factors (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.09-1.71). High NLR and low hsCRP discordance were also associated with an increased risk of MACCEs in the fully adjusted model (HR, 1.39; 95% CI, 1.05-1.84). This study demonstrated that discordantly elevated NLR levels were associated with a greater risk of adverse clinical events in patients with stable CAD, suggesting the potential clinical significance of NLR as a goal of inflammatory risk management.

Incidence and adverse clinical events of primary sclerosing cholangitis with ulcerative colitis.

The aim of this study was to conduct a nationwide population-based study to estimate the incidence of primary sclerosing cholangitis in patients with ulcerative colitis (UC-PSC) and investigate healthcare use, medication use, surgery, cancer, and death as adverse clinical events of UC-PSC. We identified incident cases of UC with (UC-PSC) or without PSC (UC-alone) between 2008 and 2018 using health insurance claims data in Korea. Univariate (crude hazard ratio (HR)) and multivariate analyses were performed to compare the risk of adverse clinical events between groups. A total of 14,406 patients with UC using population-based claims data were detected in the cohort. Overall, 3.38% (487/14,406) of patients developed UC-PSC. During a mean follow-up duration of approximately 5.92years, the incidence of PSC in patients with UC was 185 per 100,000 person-years. The UC-PSC group showed statistically more frequent healthcare use (hospitalization and emergency department visits: HRs, 5.986 and 9.302, respectively; P < .001), higher immunomodulator and biologic use (azathioprine, infliximab, and adalimumab: HRs, 2.061, 3.457, and 3.170, respectively; P < .001), and higher surgery rate (operation for intestinal obstruction, and colectomy: HRs, 9.728 and 2.940, respectively; P < .001) than did the UC-alone group. The UC-PSC group also showed significantly higher colorectal cancer and biliary tract cancer (HRs, 2.799 and 36.343, respectively; P < .001) and mortality (HR, 4.257) rates than did the UC-alone group. Patients with UC-PSC have higher risks of colorectal cancer, biliary tract cancer, and death than do patients with UC-alone. Although considered a rare disease, managing this complex and costly disease requires recognition of the impact of increased burden on healthcare services.

#2560 HEMOGLOBIN VARIABILITY AND ADVERSE CLINICAL EVENTS IN PATIENTS WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE AND ANEMIA IN CONTINUOUS CARE

Abstract Background and Aims Anemia management in non-dialysis dependent chronic kidney disease (NDD-CKD) patients has attracted attention with the introduction of new treatment options, such as prolyl hydroxylase domain enzyme inhibitors (HIF-PHI). However, studies reporting comprehensive information on anemia management in NDD-CKD patients are limited. While previous studies reported increased risks of adverse clinical events associated with hemoglobin (Hb) fluctuation in hemodialysis patients, limited information is available in NDD-CKD patients. Method A retrospective cohort study was performed using a Japanese nationwide electronic medical record-based hospital database. Patients with stage ≥3a NDD-CKD, aged ≥18 years, and at least one recorded Hb &amp;lt;11 g/dL between January 1st 2013 and April 30th 2021 were included. Patients already receiving any anemia treatment (erythropoiesis stimulating agent (ESA), iron, or HIF-PHI) were excluded. Hb levels were collected at the index date (the date of the first recorded Hb &amp;lt;11 g/dL) and during the follow-up period. Clinical events included all-cause death, cardiovascular (CV) events (myocardial infarction, unstable angina pectoris, stroke, or hospitalization for heart failure), dialysis introduction, and red-blood-cell transfusion. Time-dependent Cox proportional hazard models, adjusted by clinically relevant variables were applied to assess the risk of clinical events associated with transitioning Hb fluctuation patterns, categorized into six groups: within the target Hb range (11–13 g/dL); consistently below the target (low); consistently above the target (high); low-amplitude fluctuation around the upper limit of the target (LAH); low-amplitude fluctuation around the lower limit of the target (LAL); and, high amplitude fluctuation across the target (HA). Results Of 162,170 patients with CKD, 26,626 (16.4%) NDD-CKD patients with Hb &amp;lt;11 g/dL were identified (median follow-up length, 1.9 years). The mean age was 75.9 years, and 37.8% were female. In overall patients, the mean (±SD) Hb levels at index and at 3, 6, and 12 months of follow up were 9.9±1.2 g/dL, 10.6±1.5 g/dL, 10.8±1.6 g/dL, and 10.9±1.6 g/dL, respectively. The proportion of patients with Hb &amp;lt;10 g/dL at index and at 12 months were 34.3% and 23.9%, respectively. In the subgroup of patients treated with ESA or HIF-PHI (n = 8,876), the mean Hb (±SD) levels had increased from 9.3±1.3 g/dL to 10.3±1.5 g/dL at 3 months, 10.5±1.5 g/dL at 6 months, and 10.6±1.5 g/dL at 12 months after treatment initiation. In this subgroup, the proportion of patients with Hb &amp;lt;10 g/dL had decreased from 70.0% to 30.1% at 12 months. Fig. 1 shows the Hb levels and proportions of patients with Hb &amp;lt;10 g/dL by treatment type. During the follow-up period, 5,991 (22.5%) deaths, 3,545 (13.3%) CV events, 4,231 (15.9%) dialysis introductions, and 5,561 (20.9%) red-blood-cell transfusions were observed. The risks of clinical events were significantly higher in the low and LAL Hb groups than in the target Hb group (Fig. 2). The hazard ratios (95% CIs) for death, CV events, dialysis introduction, and red-blood-cell transfusion in the low Hb group, compared to the target Hb group were 1.35 (1.20–1.52), 1.90 (1.58–2.27), 1.75 (1.39–2.20), and 2.80 (2.28–3.43), respectively, and in the LAL Hb group were 1.28 (1.14–1.43), 1.71 (1.43–2.04), 1.85 (1.48–2.33), and 1.64 (1.33–2.02), respectively. In HA Hb group, significantly higher risks for dialysis introduction and red-blood-cell transfusion were observed. Conclusion This study reports comprehensive information on anemia management in NDD-CKD patients in clinical practice. Despite treatment for Hb correction, 20–30% of patients persistently remained at low Hb levels. The increased risk of adverse clinical events associated with Hb fluctuations suggest that stable Hb control within the target range is important to reduce the risk of mortality and morbidity in patients with NDD-CKD and anemia.

#4476 PRIMARY GLOMERULAR DISEASES AND LONG-TERM RISKS OF CKD PROGRESSION, CARDIOVASCULAR EVENTS AND DEATH: A SWEDISH NATIONWIDE COHORT STUDY

Abstract Background and Aims Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide (after diabetes and hypertension), little is known about their long-term risks and complications. Method Using data from the Swedish Renal Registry (SRR-CKD) 2005-2021, we compared clinical outcomes between patients with the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD] and membranous nephropathy [MN]) and patients with CKD attributed to non-inflammatory etiologies (i.e. without systemic auto-immune, inflammatory, infectious, hematologic malignancy, genetic disease, or polycystic kidney disease). Poisson models were used to estimate adjusted incidence rate ratios (IRR) of all-cause and cause-specific hospitalizations (cardiovascular-, acute kidney injury-, thromboembolism- and infection-related). Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) of kidney replacement therapy (KRT), major adverse cardiovascular events (MACE) and death. Results We identified 2967 patients with primary glomerular disease (71% men, age 57 years, eGFR 28 mL/min/1.73 m2, uACR 63 mg/mmol) and 40026 patients with a non-inflammatory CKD (64% men, age 74 years, eGFR 22 mL/min/1.73 m2, uACR 20 mg/mmol). As compared to non-inflammatory CKD, patients with primary glomerular diseases were younger, had a lower prevalence of cardiovascular disease, higher eGFR but higher albuminuria. Over median follow-up of 6.3 [3.3;9.9] years, there were median 3.0 [1.0;7.0] hospitalizations per patient, 9890 (23%) KRT, 11708 (27%) MACE, and 21091 (49%) deaths. As compared to non-inflammatory CKD, patients with primary glomerular disease had a lower risk of all-cause (IRR 0.77 [0.75;0.79]), and all cause-specific hospitalizations, MACE (HR 0.56 [0.50;0.63]) and death (HR 0.57 [0.52;0.62], but a similar risk of KRT (HR 1.02 [0.95;1.10]) or AKI (HR 0.84 [0.70;1.02]) (Figure 1). Within primary glomerular diseases and as compared to IgAN, patients with FSGS had a higher risk of death (HR 1.29 [1.03;1.60]) and MACE (HR 1.49 [1.12;1.97]), and patients with MN and MCD had a lower risk of KRT. Conclusion In this nationwide analysis of patients with advanced CKD undergoing nephrologist-care, those with primary glomerular disease have an observed lower risk of adverse clinical events compared to non-inflammatory CKD diseases. However, their risks of AKI or KRT are similar, emphasizing the need of adequate treatment strategies in this population. We speculate that the long-term continuous exposure to comorbidities like diabetes and hypertension in patients with non-inflammatory CKD might explain these differences. Within single primary glomerular disease etiologies, FSGS is associated with the highest risk of cardiovascular and fatal complications. The study received grant support from CSL Vifor.

Does the clot burden as assessed by the Mean Bilateral Proximal Extension of the Clot score reflect mortality and adverse outcome after pulmonary embolism?

Rapid diagnosis and risk stratification are important to reduce the risk of adverse clinical events and mortality in acute pulmonary embolism (PE). Although clot burden has not been consistently shown to correlate with disease outcomes, proximally located PE is generally perceived as more severe. To explore the ability of the Mean Bilateral Proximal Extension of the Clot (MBPEC) score to predict mortality and adverse outcome. This was a single center retrospective cohort study. 1743 patients with computed tomography pulmonary arteriography (CTPA) verified PE diagnosed between 2005 and 2020 were included. Patients with active malignancy were excluded. The PE clot burden was assessed with MBPEC score: The most proximal extension of PE was scored in each lung from 1 = sub-segmental to 4 = central. The MBPEC score is the score from each lung divided by two and rounded up to nearest integer. We found inconsistent associations between higher and lower MBPEC scores versus mortality. The all-cause 30-day mortality of 3.9% (95% CI: 3.0-4.9). The PE-related mortality was 2.4% (95% CI: 1.7-3.3). Patients with MBPEC score 1 had higher all-cause mortality compared to patients with MBPEC score 4: Crude Hazard Ratio (cHR) was 2.02 (95% CI: 1.09-3.72). PE-related mortality was lower in patients with MBPEC score 3 compared to score 4: cHR 0.22 (95% CI: 0.05-0.93). Patients with MBPEC score 4 did more often receive systemic thrombolysis compared to patients with MBPEC score 1-3: 3.2% vs. 0.6% (p < .001). Patients with MBPEC score 4 where more often admitted to the intensive care unit: 13% vs. 4.7% (p < .001). We found no consistent association between the MBPEC score and mortality. Our results therefore indicate that peripheral PE does not necessarily entail a lower morality risk than proximal PE.

Weight cycling and risk of clinical adverse events in patients with heart failure with preserved ejection fraction: a post-hoc analysis of TOPCAT.

Previous studies hardly evaluated the association of variability of body mass index (BMI) or waist circumference with clinical adverse events and investigated whether weight cycling had an effect on the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). This study was a post-hoc analysis of TOPCAT. Three outcomes were evaluated: the primary endpoint, cardiovascular disease (CVD) death, and heart failure hospitalization. Among them, CVD death and hospitalization were outcomes of heart failure. Kaplan-Meier curves were used to describe the cumulative risk of outcome and were tested using the log-rank test. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95%CIs for outcomes. We also performed a subgroup analysis, and several subgroups were compared. A total of 3,146 patients were included. In the Kaplan-Meier curves, the coefficients of variation of both BMI and waist circumference were grouped according to quartiles, with the Q4 group having the highest cumulative risk (log-rank P < 0.001). In the coefficient of BMI variation and the outcomes, the HRs for group Q4 of coefficient of variation of BMI were 2.35 (95%CI: 1.82, 3.03) for the primary endpoint, 2.40 (95%CI: 1.69, 3.40) for death, and 2.33 (95%CI: 1.68, 3.22) for HF hospitalization in model 3 (fully adjusted model) compared with group Q1. In the coefficient of waist circumference variation and the outcomes, group Q4 had increased hazard of the primary endpoint [HR: 2.39 (95%CI: 1.84, 3.12)], CVD death [HR: 3.29 (95%CI: 2.28, 4.77)], and HF hospitalization [HR: 1.98 (95%CI 1.43, 2.75)] in model 3 (fully adjusted model) compared with group Q1. In the subgroup analysis, there was a significant interaction in the diabetes mellitus subgroup (P for interaction = 0.0234). Weight cycling had a negative effect on the prognosis of patients with HFpEF. The presence of comorbid diabetes weakened the relationship between waist circumference variability and clinical adverse events.

Novel insights into diminished cardiac reserve in non-obstructive hypertrophic cardiomyopathy from four-dimensional flow cardiac magnetic resonance component analysis.

Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk. Fifty-one participants (37 non-obstructive HCM and 14 matched controls) underwent 4D-flow CMR. Left-ventricular (LV) end-diastolic volume was separated into four components: direct flow (blood transiting the ventricle within one cycle), retained inflow (blood entering the ventricle and retained for one cycle), delayed ejection flow (retained ventricular blood ejected during systole), and residual volume (ventricular blood retained for >two cycles). Flow component distribution and component end-diastolic kinetic energy/mL were estimated. HCM patients demonstrated greater direct flow proportions compared with controls (47.9 ± 9% vs. 39.4 ± 6%, P = 0.002), with reduction in other components. Direct flow proportions correlated with LV mass index (r = 0.40, P = 0.004), end-diastolic volume index (r = -0.40, P = 0.017), and SCD risk (r = 0.34, P = 0.039). In contrast to controls, in HCM, stroke volume decreased with increasing direct flow proportions, indicating diminished volumetric reserve. There was no difference in component end-diastolic kinetic energy/mL. Non-obstructive HCM possesses a distinctive flow component distribution pattern characterised by greater direct flow proportions, and direct flow-stroke volume uncoupling indicative of diminished cardiac reserve. The correlation of direct flow proportion with phenotypic severity and SCD risk highlight its potential as a novel and sensitive haemodynamic measure of cardiovascular risk in HCM.

Association of Clinical Outcomes With Sex in Patients Receiving Chronic Maintenance Antiplatelet Monotherapy After Percutaneous Coronary Intervention: A Post Hoc Gender Analysis of the HOST-EXAM Study.

Background Clopidogrel monotherapy was more effective in reducing the risk of adverse clinical events than aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES), according to the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it remains unknown whether these effects differ based on sex. Methods and Results This was a prespecified secondary analysis of HOST-EXAM in South Korea. Patients who maintained dual antiplatelet therapy without adverse clinical events for 6 to 18 months after PCI with DES were included. The primary end point was a composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, or Bleeding Academic Research Consortium (BARC) bleeding type ≥3 at 24 months after randomization. The bleeding end point was BARC types 2 to 5. The primary end point was comparable between the sexes (adjusted hazard ratio [HR], 0.79 [95% CI, 0.62-1.02]; P=0.067), and the bleeding end point (adjusted HR, 0.79 [95% CI, 0.54-1.17]; P=0.240) was also similar. Compared with aspirin, clopidogrel was associated with lower risk of primary composite end point (adjusted HR, 0.70 [95% CI, 0.55-0.89]; P=0.004) and bleeding end point (adjusted HR, 0.65 [95% CI, 0.44-0.96]; P=0.031) in men but not in women. Conclusions The primary composite end point and bleeding events were comparable between the sexes during chronic maintenance antiplatelet monotherapy after PCI with DES. Clopidogrel monotherapy, compared with aspirin, significantly reduced the risk of the primary composite end point and bleeding events in men. However, the beneficial effect of clopidogrel on the primary end point and bleeding events was mitigated in women. Registration Information clinicaltrials.gov. Identifier: NCT02044250.

Papel de los niveles circulantes del antígeno carbohidrato 125 para identificar al paciente no frágil con IC

Introduction and objectivesHeart failure (HF) is an age-related syndrome with a high burden of frailty. However, frailty assessment is not regularly performed in clinical practice. Therefore, a clinical tool for frailty assessment is still required. High levels of Plasma carbohydrate antigen 125 (CA125) are related with a higher risk of adverse clinical events. In this study we aimed to evaluate different CA125 values and its association with frailty categories in HF. MethodsIn this observational, single-center and prospective study, frailty was assessed by Fried score along with the baseline characteristics of the HF stable patient. The discriminative ability of CA125 for predicting frailty status was evaluated by receiver operating characteristic (ROC). ResultsIn 277 patients (74±10 years, 42.59% women, 52.70% left ventricular ejection fraction <50% and 81.22% New York Heart Association grade I-II). There were 61 (22.02%) robust (Fried=0), 95 (34.29%) pre-frail (Fried=1-2) and 121 (46.68%) frail (Fried ≥ 3). CA125 values were lower in robust (13 U/mL (9-23) vs 19 U/mL (12-41), P=.002) and values ≤ 10 U/mL showed a negative predictive value of 66% to rule out the pre-frail/frailty status. Significant, positive, and non-linear association between CA125 and the Fried score (P=.003) was found. CA125 values ≤ 10 U/mL showed a high probability of the presence of robustness. ConclusionsIn a cohort of patients with chronic HF, low values of CA125 (< 10 U/mL) predicted robust patients.

Clinical characteristics and prognosis differences between isolated right and left ventricular myocardial infarction in the Chinese population: a retrospective study.

Acute myocardial infarction (AMI) is divided into left ventricular myocardial infarction (LVMI) and right ventricular myocardial infarction (RVMI) according to the regions of myocardial ischemic necrosis. Clinical characteristics, treatment strategies, and prognosis differences between isolated RVMI and LVMI have not been well characterized. This study aimed to explore this difference of patients with isolated RVMI and LVMI. This retrospective cohort study included 3,506 patients hospitalized with coronary angiography diagnosed type 1 myocardial infarction (MI). Characteristics of admission and treatment strategies were compared in patients with isolated RVMI and LVMI. COX proportional hazards models with and without inverse probability of treatment weighting (IPTW) adjustment were performed to estimate the difference in all-cause and cardiovascular mortality between the two groups. In this retrospective study, we found the frequency of isolated RVMI was significantly lower in the population than that of isolated LVMI (406 (11.6%) vs 3,100 (88.4%)). Patients with isolated RVMI have similar age, sex, and comorbidities to the patients with isolated LVMI. However, patients with isolated RVMI have lower heart rate and blood pressure, but higher rates of cardiogenic shock and atrioventricular block. It is noteworthy that patients with isolated RVMI are more likely to be complicated with the multivessel lesion. Patients with isolated RVMI have lower risk of all-cause mortality (HR 0.36; 95% CI [0.24-0.54], p < 0.001) and cardiovascular mortality (HR 0.37; 95% CI [0.22-0.62], p < 0.001) than patients with isolated LVMI. This study showed that patients with isolated RVMI and LVMI have similar baseline characteristics. However, the clinical manifestations were different in the isolated RVMI and LVMI patients. This study revealed a better prognosis of isolated RVMI patients compared to isolated LVMI, which indicates the ischemic region could be considered in AMI risk stratification models for better assessment of risk for adverse clinical events.

P659 Continuing or stopping 5-aminosalicylate in patients with Inflammatory Bowel Disease under anti-TNF therapy: A nationwide population-based study

Abstract Background The clinical impact of continuing or stopping 5-aminosalicylate (5-ASA) after escalating to treatment with an anti-tumour necrosis factor (TNF) agent in patients with inflammatory bowel disease (IBD) is currently unclear. We aimed to compare the outcomes of IBD patients who stopped or continued 5-ASA after starting anti-TNF therapy. Methods We analysed data obtained from the Korean National Health Insurance claims database between 2007 and 2020. Our analysis included IBD patients already on 5-ASA treatment who started anti-TNF treatment. We compared the prognosis of patients who stopped 5-ASA within 90 days of anti-TNF initiation with those who continued 5-ASA. The primary outcome was any adverse clinical event defined as a composite of intestinal surgery, IBD-related hospitalization, or new corticosteroid use. Kaplan-Meier method and Cox proportional hazards models at landmark time were used to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results Among 62,262 patients diagnosed with IBD during the study period, 7,442 patients were included for analysis. A total of 1,037 (13.9%) patients discontinued 5-ASA within 90 days of starting anti-TNF therapy (Figure 1). Among the included patients, 4,479 (60.2%) had Crohn’s disease, while 2,963 (39.8%) had ulcerative colitis (Table 1). Discontinuation of 5-ASA was not associated with an increased risk of any adverse clinical events, as well as its component outcomes of intestinal surgery, IBD-related hospitalization, and corticosteroid use, with aHRs of 1.011 (95% CI, 0.934 to 1.095), 0.954 (95% CI 0.760 to 1.198), 0.995 (95% CI 0.894 to 1.107), and 0.969 (95% CI, 0.890 to 1.056), respectively (Table 2). In addition, the cumulative incidence of each adverse clinical event, as well as the composite outcome, were not significantly different between the two groups (all, p &amp;gt; 0.05) (Figure 2). Subgroup analysis by sex, IBD type, the timeframe of anti-TNF use, pre-anti-TNF 5-ASA use duration, pre-anti-TNF corticosteroid use, pre-anti-TNF hospitalizations, pre-anti-TNF emergency department visits, and anti-TNF agent type also showed no significant difference in the development of adverse clinical events between the two groups. Conclusion In this nationwide population-based study, we observed that discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse clinical events.