Worse Clinical Outcomes Research Articles

Which blood pressure metrics should be used in patients on dialysis?

Remarkable progress has recently been achieved in blood pressure (BP) control based on key research findings in the general population. It has been observed that maintaining BP slightly lower than previously recommended goals leads to better clinical outcomes, provided that patients can tolerate it. Previously, BP control targets for dialysis patients were extrapolated from studies conducted on the general population. However, dialysis patients are considered a distinct group with unique characteristics, which makes defining appropriate BP targets a matter of debate. Several observational studies measuring BP in hemodialysis (HD) patients within dialysis units have shown that lower peridialysis BP (pre-, post-, and interdialytic BP) is associated with worse clinical outcomes. However, this association is likely confounded by factors specific to dialysis patients. The relationship between BP and mortality appears to be more linear in patients with fewer underlying cardiovascular diseases and longer survival. Recent studies have indicated that BP measurements taken outside of dialysis sessions, such as standardized BP on nondialysis days, home BP, and ambulatory BP monitoring between HD sessions, are more predictive of clinical outcomes. Due to the varied effects of dialysis-related treatment practices on BP, there is a lack of data from large-scale clinical trials. As a result, it is challenging to provide strong recommendations for BP targets directly applicable to dialysis patients. This review addresses various factors influencing BP in dialysis patients, including the establishment of individualized target BP levels and discussions on maintenance strategies, while incorporating a recent literature review.

CTNI-59. RARE AND NOVEL KIAA1549-BRAF FUSION BREAKPOINTS PREDICT POOR CLINICAL OUTCOME FOR PATIENTS WITH RECURRENT OR PROGRESSIVE PEDIATRIC LOW-GRADE GLIOMA: PHASE II PNOC001 TRIAL RESULTS

Abstract OBJECTIVES PNOC001 sought to estimate progression-free survival (PFS) associated with everolimus for progressive/recurrent pediatric low-grade glioma (pLGG) and to determine if activated PI3K/AKT/mTOR pathway as measured by positive phosphorylated-ribosomal protein S6 (p-RPS6) was associated with response. A secondary objective was to assess whether somatic drivers influence median PFS. METHODS Patients, 3-21 years of age, with recurrent/progressive pLGG received everolimus orally at 5 mg/m2 daily. Somatic drivers, when available, were associated with PFS and compared to four independent molecular pLGG cohorts with newly-diagnosed and progressive/recurrent patients. RESULTS From 2012 to 2019, 65 subjects enrolled [median age 9.6 years, 3.0-19.9; 46% female]; Median PFS for all-comers was 11.1 months (95%-CI 7.6-19.8, n = 64). PFS was not modulated by PI3K/AKT/mTOR pathway activation (median PFS 11.2 vs 9.4 months, P = 0.83, n = 62). BRAF alterations were identified in 67.8% (40/59) of patients. Rare/novel KIAA1549-BRAF fusion breakpoints were enriched in PNOC001 compared to newly-diagnosed pLGGs in independent cohorts (28.6% vs 2.6%, P = 1.4e-4, n = 214). In PNOC001, patients with rare/novel KIAA1549-BRAF fusion breakpoints had worse clinical outcomes than patients with common fusion breakpoints (median PFS 6.1 vs 16.7 months, P < 0.05, n = 20). Rare/novel KIAA1549-BRAF fusion breakpoints were also enriched in patients with progressive/recurrent disease in independent pLGG cohorts (17.6% vs 2.6%, P = 2e-3, n = 227). Integration of BRAF alterations and DNA methylation-based tumor subtypes further revealed that rare/novel KIAA1549-BRAF fusion breakpoints are more frequent in supratentorial midline (14.1%) compared to infratentorial (2.0%) pilocytic astrocytomas (P = 1e-4). KIAA1549-BRAF fusion breakpoints remained risk factors for progressive/recurrent disease in PNOC001 (P = 0.05) and independent pLGG cohorts (P < 0.05) after accounting for tumor location and DNA methylation subtypes. CONCLUSIONS Rare/novel KIAA1549-BRAF fusion breakpoints are more frequent in supratentorial midline pLGGs and define independent genomic risk factors for disease progression/recurrence. Our results indicate that future clinical trials must interrogate and define KIAA1549-BRAF fusion breakpoints for informative results and conclusions.

Influence of socioeconomic status on the presence of obstructive coronary artery disease and cardiovascular outcomes in patients undergoing invasive coronary angiography

Abstract Background Although it has been documented that low socioeconomic status (SES) is associated with increased risk of mortality and cardiovascular disease (CVD), this issue has not been addressed in patients at high CVD risk. This study was performed to investigate the association of the patient’s SES with the presence of obstructive coronary artery disease (CAD) and long-term cardiovascular outcomes who undergo invasive coronary angiography (ICA). Methods A total of 9,530 patients who underwent ICA for the evaluation and treatment of CAD (66.0 ± 12.3 years and 60.2% male) were retrospectively reviewed. The patients were divided into two groups according to the health insurance type: those with low SES who had the Medical aid program (Medical aid beneficiary [MAB] group; n = 1,436) and those with high SES who had the National Health Insurance program (National Health Insurance beneficiary [NHIB] group; n = 8,094). The primary outcome was a composite of cardiac death, acute myocardial infarction, coronary revascularization, and ischemic stroke. Results Of the study patients, 1,436 (15.1%) were in the MAB group. The prevalence of cardiovascular risk factors was higher in the MAB group compared to the NHIB group. However, the prevalence of obstructive CAD was similar between the two groups (62.8% vs. 64.2%; p = 0.306). During a median follow-up period of 3.5 years (interquartile range, 1.0-5.9 years), the incidence of the composite cardiovascular event was significantly higher in the MAB group than in the NHIB group (20.2% vs. 16.2%, p < 0.001). In multivariable Cox regression analysis, compared to the NHIB group, the MAB group was independently associated with worse clinical outcomes even after controlling for potential confounders (adjusted odds ratio, 1.28; 95% confidence interval, 1.07-1.54; p = 0.006). Conclusions Although CAD prevalence was similar, MABs showed an increased risk of composite cardiovascular events than NHIBs in Korean adults undergoing ICA. This provides additional evidence for the association between low SES and an increased risk of CVD, even in high-risk subjects.

Selenium deficiency is associated with anemia in heart failure patients - The HARVEST Study

Abstract Background Heart failure (HF) patients with anemia have worse clinical outcomes with increased hospitalization rates, decreased exercise tolerance, and higher mortality compared to those without anemia. Previous studies have indicated a correlation between selenium deficiency and anemia in healthy elderly individuals and in pregnant women. The BIOSTAT-CHF study reported that HF patients with higher selenium levels were less likely to have anemia or iron deficiency. These studies suggest that selenium deficiency can lead to the development of anemia. However, studies regarding this association in HF patients are limited. Purpose The purpose of this study was to examine the relationship between selenium deficiency, measured by selenoprotein P (SELENOP) levels, and anemia, hemoglobin levels, and iron state in subjects with acute HF. Methods SELENOP, a well-validated plasma marker of selenium status, was measured in 320 subjects hospitalized for HF in the Swedish HeArt and bRain failure inVESTigation trial (the HARVEST study). Of these subjects, 310 had complete data on all covariates. Prior to analyses, skewed variables were ln-transformed. The relationships between continuous SELENOP levels and 1) Hb levels, 2) anemia (Hb < 115 g/L (women), < 130 g/L (men)), and 3) iron status (as measured by transferrin receptor 1 (TfR1) which increase in iron deficiency) were evaluated using multivariable logistic and linear regression models adjusting for age, sex and renal function (cystatin C). Additionally, selenium deficiency was defined as SELENOP levels in the lowest quartile and its association with anemia, hemoglobin, and iron state was explored in multivariable logistic and linear models. Results Anemia was present in 133 subjects (42.9%). SELENOP levels were positively correlated with hemoglobin levels (0.238; p = 2.3x10-5) and negatively associated with TfR1 levels (-0.238, p = 2.0x10-6). In multivariable linear regression models, each 1 standard deviation increase in SELENOP was linked to higher Hb levels and lower TfR1 levels (Table 1). Furthermore, selenium deficiency was associated with lower Hb levels, higher TfR1 levels, and higher odds of anemia in HF patients (Table 1). Conclusions In acute heart failure patients, lower levels of selenoprotein P were associated with lower hemoglobin levels, higher transferrin receptor 1 levels, and a higher prevalence of anemia.

Colistin plasma concentrations are not associated with better clinical outcomes in patients with pneumonia caused by extremely drug-resistant Pseudomonas aeruginosa.

The objective of this study was to examine the relationship between colistin plasma concentrations and clinical outcomes in patients with hospital-acquired pneumonia (HAP) caused by extensively drug-resistant Pseudomonas aeruginosa (XDR-PA). A prospective observational cohort study was conducted at a tertiary care hospital. Patients diagnosed with HAP caused by XDR-PA between January 2010 and September 2018 were included. Steady-state plasma concentrations (Css,avg) of colistin were measured by high performance liquid chromatography (HPLC). Based on the pharmacokinetic/pharmacodynamic data of colistin in animal models, previous clinical data, and the minimum inhibitory concentration (MIC) of the most prevalent strain in our center, an area under the ROC curve (AUC)/MIC24h between 30 and 60 mg·h/L was considered optimal. The primary outcome was 30-day mortality, and the secondary outcomes were clinical cure and colistin-associated nephrotoxicity. Seventy-five patients were included. The median Css,avg was 1.1 (0.56-1.75) mg/L and only 23 (30.7%) patients achieved an AUC/MIC24h of 30-60 mg·h/L and the 30-day mortality was 30.7%. In multivariate analysis, sequential organ failure assessment score [adjusted hazard ratio (95% confidence interval, CI) 1.19 (1.07-1.32)] and high AUC/MIC24h (hazard ratio 1.55, 95% CI 1.17-2.04, P = 0.002) were associated with increased risk of death and clinical failure. Based on the maximally selected standardized log-rank statistic, the Css,avg cutoff point that best predicted mortality was 1.5 mg/L. Nephrotoxicity at the end of treatment was 38.7%. High colistin exposure was not associated with improved clinical outcomes in the setting of HAP caused by XDR-PA. These data suggest that caution is required with intravenous colistin for the treatment of HAP caused by XDR-PA.IMPORTANCEIn some cases, colistin is the only treatment option for infections caused by the very drug-resistant Pseudomonas aeruginosa. However, in the past decade, there have been questions concerning its pharmacokinetics and concentration at the site of infection. In this scenario, its use in a difficult-to-treat infection like pneumonia is currently debatable. This is a clinical pharmacokinetic study of colistin in patients with multidrug-resistant P. aeruginosa pneumonia. Our findings demonstrate that colistin exposure is associated with worse clinical outcomes rather than better clinical outcomes, implying that other therapeutic options should be explored in this clinical setting.

Arterial hypertension, chronic kidney and severe valvular heart disease predict worse outcome after postponing non-emergency cardiac interventions during the COVID-19-pandemic

Abstract Background Deferral of non-emergency cardiac procedures is associated with increased early emergency cardiovascular hospitalizations. Criteria to identify patients at risk for adverse events when postponing their scheduled intervention are needed. Aim The aim of this study was to identify predictors associated with worse clinical outcome in cardiac patients whose non-emergency cardiovascular intervention has been deferred during the COVID-19 pandemic. Methods This monocentric retrospective study included patients whose non-emergency cardiac intervention has been postponed during COVID-19-related lockdown between March 19th and April 30th 2020. Cox regression was performed to identify predictors of the combined endpoint emergency cardiovascular hospitalization and death. Patients’ outcome after 12 months was compared to a seasonal control group undergoing non-emergency interventions in 2019 as scheduled. Results The combined endpoint of death and emergency cardiovascular hospitalization occurred in 70 (36.5%) of 193 patients with a postponed cardiovascular intervention. The planned intervention was deferred by a median of 23 [19 – 36] days. Arterial hypertension (Hazard ratio [HR] 2.27; 95%-Confidence interval [CI] 1.00-5.12; P=0.049), chronic kidney disease (HR 1.89; 95%-CI 1.03 – 3.49, P=0.041) as well as severe valvular heart disease (HR 3.08; 95%-CI 1.68-5.64; P<0.001) were independent predictors of death or emergency hospitalization. Kaplan-Maier estimators of the combined endpoint were 31% in patients with arterial hypertension, 56% in patients with severe valvular heart disease and 77% with both risk factors (HR 12.4, 95%-CI 3.8-40.7; P<0.001) and only 9% in patients without these risk factors (log rank P<0.001). Separate analyses of patients with arterial hypertension, chronic kidney disease and severe valvular heart disease revealed that deferred patients showed significantly poorer clinical outcomes when compared to the control group 2019 (log rank P<0.001, P=0.006 and P<0.001, respectively). NT-proBNP cut-off ≥ 1,109 pg/ml best predicts the occurrence of primary endpoint event in deferred patients (AUC 0.71; P<0.001; sensitivity 64%, specificity 69%). Conclusion Our results suggest that patients with either arterial hypertension, chronic kidney or severe valvular heart disease are at very high risk for emergency hospitalization and increased mortality in case of postponed cardiac interventions even in supposed stable clinical status. Risk is even higher in patients suffering from a combination of these conditions. In addition, measuring NT-proBNP levels might help to identify those at high or very high risk.

Anti-diabetic medication adherence and cardiovascular outcomes in patients with cancer: a nationwide population-based cohort study

Abstract Background Diabetes is an important cause of morbidity, which predisposes patients to major cardiovascular (CV) events and mortality. However, clinical implications of anti-diabetic medication adherence for cancer patients have not been well studied in the real clinical practice. Purpose This study aimed to evaluate the association between anti-diabetic medication adherence and clinical outcomes in adult patients with cancer. Methods Using the prospective nationwide cohort (Korean NHIS-NSC), we extracted adult cancer patients treated with anti-diabetic medications. Based on the medication possession ratio (MPR) value, participants were divided into 3 groups: good (MPR ≥0.8), moderate (0.5 ≤ MPR < 0.8), and poor (MPR<0.5) adherence groups. The primary outcomes were overall and CV mortality. The secondary outcome was CV events requiring hospitalization due to major CV diseases. Results Among 8,052 cancer patients with concomitant diabetes, 59.4% were nonadherence group (21.5% were moderate and 37.9% were poor adherence group). Over a median of 8.4 years of follow-up, 1,475 deaths and 2,931 CV events occurred. Compared to the good adherence group, the moderate and poor adherence groups had a 1.61-fold and 2.00-fold increased risk for overall mortality; and 1.66-fold and 1.98-fold elevated risk for CV mortality, respectively, after adjustment for possible confounders. Furthermore, moderate and poor adherence groups had a 1.29-fold and 1.38-fold elevated risk for new-onset CV events. These trends were consistent across CV event subtypes. Conclusions Nonadherence to anti-diabetic medication is common in cancer patients and is associated with worse clinical outcomes in adult cancer patients with diabetes. More attention should be paid to improve adherence to anti-diabetic medication among patients with cancer.

Antitumor activities against breast cancers by an afucosylated anti-HER2 monoclonal antibody H2 Mab-77-mG2a -f.

Breast cancer patients with high levels of human epidermal growth factor receptor 2 (HER2) expression have worse clinical outcomes. Anti-HER2 monoclonal antibody (mAb) is the most important therapeutic modality for HER2-positive breast cancer. We previously immunized mice with the ectodomain of HER2 to create the anti-HER2 mAb, H2 Mab-77 (mouse IgG1 , kappa). This was then altered to produce H2 Mab-77-mG2a -f, an afucosylated mouse IgG2a . In the present work, we examined the reactivity of H2 Mab-77-mG2a -f and antitumor effects against breast cancers invitro and invivo. BT-474, an endogenously HER2-expressing breast cancer cell line, was identified by H2 Mab-77-mG2a -f with a strong binding affinity (a dissociation constant [KD ]: 5.0 × 10-9 M). H2 Mab-77-mG2a -f could stain HER2 of breast cancer tissues in immunohistochemistry and detect HER2 protein in Western blot analysis. Furthermore, H2 Mab-77-mG2a -f demonstrated strong antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) for BT-474 cells. MDA-MB-468, a HER2-negative breast cancer cell line, was unaffected by H2 Mab-77-mG2a -f. Additionally, in the BT-474-bearing tumor xenograft model, H2 Mab-77-mG2a -f substantially suppressed tumor development when compared with the control mouse IgG2a mAb. In contrast, the HER2-negative MDA-MB-468-bearing tumor xenograft model showed no response to H2 Mab-77-mG2a -f. These findings point to the possibility of H2 Mab-77-mG2a -f as a treatment regimen by showing that it has antitumor effects on HER2-positive breast tumors.

Predictive value of d-dimer for plaque rupture, thrombus and worse clinical outcomes in acute coronary syndrome from TACTICS registry

Abstract Background Acute coronary syndrome (ACS) mainly occurs by the rupture of lipid plaques with platelet aggregation. D-dimer (DD) is a primary degradation product and circulating marker of fibrinolysis. The use of DD helps to diagnose thrombosis. The serum DD level may indicate a thrombus within coronary artery in patients with ACS. Purpose The present study determined the association of serum DD level on admission with a thrombus within culprit lesion and ACS mechanism assessed by optical coherence tomography (OCT), and clinical outcomes. Methods and Results Tokyo/ Kanagawa/ Chiba/ Shizuoka/ Ibaraki active OCT applications for ACS (TACTICS) registry includes 695 consecutive ACS patients who underwent emergent PCI with OCT guidance. Of those, the information of serum DD level was available in 653 cases. Those patients were divided into two groups according to serum DD level on admission: high DD group(≧0.73 μg/ml, n= 328) and low DD group(＜0.73 μg/ml, n= 325). Comparison of type of plaque morphology and thrombus are shown in Figure. ACS patients with high DD level had poor long-term outcomes. Conclusion High serum DD level was associated with red-thrombus, plaque rupture, and worse prognosis in ACS. The simple test of DD may give us useful information in clinical practice for ACS.

Impact of kidney function, ticagrelor and genetic polymorphism on high platelet reactivity

Abstract Background High platelet reactivity (HPR) is associated with worse clinical outcomes. Patients with chronic kidney disease (CKD) respond poorly to clopidogrel. The purpose was to investigate what is major determinant on HPR in CKD patients. Methods A total of 219 (139 normal kidney function, 80 CKD) patients who were treated with clopidogrel or ticagrlor were assessed platelet reactivity and genetic polymorphisms. Platelet function was evaluated by the VerifyNowTM P2Y12 assay. Genes tested were ABCB1, PON1, cytochrome P450 (CYP) 2C19, CYP2C9 and P2Y12. HPR was defined as P2Y12 reaction units ≥ 230. Results Platelet reactivity were significantly higher in patients with CKD compared to normal kidney function (288 ± 96 vs 223 ± 69, p < 0.01). But, there were no significant differences of genetic distribution between 2 groups. In patients with CKD and normal kidney function, CYP2C19 carriers had greater platelet reactivity during clopidogrel therapy but there were no differences during ticagrelor treatment regardless of CYP2C19 status (Figure). In multivariate analysis, CKD [hazard ratio (HR): 4.67 (2.27 – 9.78), p < 0.01], CYP2C19 carriers [HR: 2.81 (1.36 – 5.82), p < 0.01] and ticagrelor treatment [HR: 0.29 (0.18 – 0.48), p < 0.01] were significantly correlated with HPR. Conclusion Ticagrelor treatment achieved greater platelet inhibition in patients with CKD whereas CKD and CYP2C19 genotype were significantly correlated with HPR.

Relationship of clinical complexity domains to management and outcomes of european and asian patients with atrial fibrillation: a comparison of two regional prospective observational AF registries

Abstract Background Clinical complexity domains, defined as multimorbidity, frailty and polypharmacy, have been associated with worse clinical outcomes in atrial fibrillation (AF) patients. Differences between European and Asian patients in the prevalence of these clinical complexity domains, the differential prescription of oral anticoagulant (OAC) and risks of clinical outcomes remain unclear. Purpose To examine the epidemiology and impact of clinical complexity domains in a large prospective cohort of European and Asian AF patients on OAC prescriptions and the risk of clinical outcomes. Methods We studied AF patients derived from two large prospective observational AF registries, conducted in Europe and Asia, on the basis of the same electronic case report form. Multimorbidity and polypharmacy were defined according to the number of comorbidities and drugs at baseline, while frailty was defined according to a 40-items frailty index (FI). Prescription of OAC was assessed at baseline. The primary clinical outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Logistic and Cox regression analyses were used to determine associations with domains, and interaction analyses were performed to investigate differences between European and Asian patients. Results European patients had a higher burden of all three clinical complexity domains (Multimorbidity: 79.5% European vs 70.2% Asian, p<0.001; Frailty: 21.3% European vs 7.8% Asian, p<0.001; Polypharmacy: 53.9% European vs 36.7% Asian, p<0.001). At baseline, Asian patients with multimorbidity, frailty and polypharmacy were less likely prescribed with OAC than European ones, with the largest difference seen in frail patients (83.0% European vs 76.2% Asian, p=0.003). After adjustments, being frail was associated with lower OAC prescription (OR 0.45, 95% CI 0.39-0.52), while Asian patients were less likely prescribed OAC than Europeans (OR 0.34, 95% CI 0.25-0.45 vs. OR 0.47, 95% CI 0.40-0.55, Pint=0.037). Adjusted Cox regression found that in the overall population, clinical complexity domains were associated with a higher risk of composite outcome, all-cause death, and MACEs [Figure 1]. On subgroup analysis, frail Asian patients had a higher risk of composite outcome (Pint= 0.003) compared with Europeans [Figure 1]. Similarly, a higher risk of all-cause death was found among Asians [Figure 1] for all the three clinical complexity domains [Figure 1]. Conclusions Clinical complexity domains have different epidemiological characteristics amongst European and Asian AF patients, being more prevalent in Europeans. These domains differently affect European and Asian patients in terms of OAC use. The presence of clinical complexity domains increases the risk of several clinical outcomes, with Asian patients being burdened with a much higher risk compared to Europeans.Figure 1

The significance of excessive supraventricular ectopic activity immediately after catheter ablation in the risk stratification for late recurrence of atrial fibrillation

Abstract Background/Introduction Early recurrence of atrial fibrillation (AF) (<3 months) after ablation is associated with late recurrence (≥3 months). Even absent early AF recurrence, patients frequently experience postprocedural supraventricular ectopic complexes (SVEC). Excessive supraventricular ectopic activity (ESVEA) is a new surrogate marker for new-onset AF and poor stroke prognosis. However, the relationship between ESVEA and late recurrence of AF post-ablation is poorly understood. Purpose We hypothesized that postprocedural ESVEA would be associated with late recurrence of AF. We also investigated use of ESVEA compared to early recurrence of AF for stratifying patients’ risk of late recurrence of AF. Methods Participants were patients with AF who underwent initial radiofrequency catheter ablation and 24-Holter monitoring the day after the procedure between 2014 and 2020. SVEC was defined as supraventricular complexes occurring ≥30% earlier than expected compared with the previous RR interval. ESVEA was defined as at least 30 beats of SVEC per hour, or any episodes of SVEC runs ≥20 beats. Atrial tachyarrhythmia lasting for longer than the 30s was defined as AF recurrence. We analyzed the association between postprocedural Holter monitoring results and late recurrence of AF. Results We enrolled 469 patients with AF (average ± SD 63.6 ± 10.1 years; 32% female; 56% paroxysmal AF). We observed early recurrence of AF (n = 57; 12%) and ESVEA (n = 287; 61%) during postprocedural Holter monitoring in these patients; 125 patients (27%) had no signs of AF or ESVEA. During a median follow-up of 25 months, 152 patients (32%) experienced a late recurrence of AF. Patients who demonstrated early AF recurrence or ESVEA during Holter monitoring were significantly more likely to experience late recurrence of AF, even after adjusting for various clinical parameters and left atrial enlargement. Patients with early recurrence of AF had the worst outcomes, and AF-free survival was significantly worse in patients with ESVEA than patients without early recurrence of AF (Figure). Conclusions ESVEA on post-procedure day 1, even without AF, was associated with worse clinical outcomes following initial AF ablation. Postprocedural 24-Holter monitoring may reveal an increased risk of late recurrence of AF secondary to observation of recurrent AF or ESVEA.

Side branch closure in patients undergoing coronary bifurcation stenting with or without side branch predilatation

Abstract Background Considerable progress in the treatment of coronary bifurcation lesions has been achieved. Side branch pre-dilatation (SPPD) is a technique that is generally not recommended by the latest guidelines and consensus statements. The main reason is the risk of side branch (SB) dissection or vessel closure. Aim The aim of the current study is to explore the rates of SB closure in patients undergoing bifurcation PCI with or without SB pre-dilatation. Methods All patients with coronary bifurcation lesions treated between 2012 and 2022 were included in the prospective registry. For the current analysis, only patients with stable or unstable angina were included, with follow-up of at least two years. Patients with STEMI and left main stenosis were excluded. Propensity Score Matching (PSM) was performed to equalize the effects of the following characteristics: age, sex, diabetes, smoking, hypertension, dyslipidemia, renal failure, cancer, COPD, atrial fibrillation, left ventricular ejection fraction, and SYNTAX score. SB closure was defined as SB ostial stenosis ≥99% with TIMI 0-1 flow. Results 832 patients from the registry covered the criteria for the current analysis. After PSM, 324 matched couples remained, and 648 patients were analyzed. The demographic characteristics of SBP(+) and SBP (-) were well balanced, with no differences between groups – age 68±10 years, 71% males, 40% smokers, 47% with diabetes, 26% with previous MI, 53% with previous PCI, 4% after CABG, 12% with peripheral arterial disease, 13% with COPD, 32% with renal failure, 23% AFib, LVEF 55±10%. Patient with SBP(+) wad more CTOs (17% vs. 9%, p=0.003), longer lesions (42±21mm vs. 36±20mm, p<0.001) and more severe SB stenoses (68%±25% vs. 41%±31%, p<0.001). Among true bifurcation stenoses (Medina xx1 – 63%, 410/648), 88% were predilated. SB closure was non-significantly different in groups with SBPD and SBnPD (3.6% vs. 2.2%, p=0.272). Acute SB closure after stenting occurred at similar rates in SBPD and SBnPD groups (3.6% vs. 2.7%, p=0.505), without difference in rates of MI if SB was closed or not (n=10/17, 59% vs. n=227/631, 36%, p=0.058). The rate of periprocedural MI was not significantly different between groups with and without SB closure – 52% vs. 34%, p=0.066. At the end of the procedure, only 7 SBs were closed, 2 in the SBPD group and 5 in the SBnPD group (p=0.461). Conclusions The rates of final SB closure were numerically lower (but not significantly different) when SBPD was performed. SB closure did not translate into worse clinical outcomes.

Comparisons of effectiveness and safety between different dosage strategy in patients with atrial fibrillation treated with rivaroxaban: a systemic review and meta-analysis

Abstract Background Limited real world data show that rivaroxaban following dosage criteria from either ROCKET AF (15mg/day or 10mg/day if creatinine clearance (CrCl)<50ml/min) or J-ROCKET AF (15mg/day or 10mg/day if CrCl<50ml/min) are associated with comparable risks of thromboembolism and bleeding with each other in patients with non-valvular atrial fibrillation (NVAF). We aimed to study whether these observations differ between Asian and non-Asian subjects. Methods Databases were searched for adjusted observational study that compared relevant clinical outcomes of NVAF patients receiving off-label under-dosing rivaroxaban (10mg/day if CrCl>50ml/min), on-label dose rivaroxaban eligible for ROCKET AF or J-ROCKET AF, and off-label over-dosing rivaroxaban (20mg/day if CrCl<50ml/min). Results Eighteen studies were included. Rivaroxaban following J-ROCKET AF criteria (n=19,513) was associated with comparable risks of thromboembolism in the Asian subgroup (n=43,076), whereas rivaroxaban following J-ROCKET AF criteria (n=8555) was associated with higher risks of thromboembolism (hazard ratio (HR):1.27;[95% confidential interval (CI):1.05–1.53]) and all-cause mortality (HR:1.30;[95%CI:1.05–1.60]) compared with that of ROCKET AF criteria (n=23,139) in the non-Asian subgroup (n=31,694)(Figure). There was no differences in risks of major bleeding between rivaroxaban following J-ROCKET AF versus ROCKET AF criteria either in the Asian or non-Asian subgroup (Figure). Off-label underdosed rivaroxaban 10mg (n=6305) was associated with a higher risk of thromboembolism (HR:1.64;[95%CI:1.28–2.11]) but lower risk of major bleeding (HR:0.72;[95%CI:0.57–0.90]) compared with eligible dosage criteria (n=11,673). Off-label overdosed rivaroxaban 20mg (n=7572) was associated with worse clinical outcomes in the risks of thromboembolism (HR:1.42;[95%CI:1.14–1.79]), mortality (HR:1.41;[95%CI:1.15–1.73]) and major bleeding (HR:1.27; 95%CI:1.05–1.54; N=7 with I2=25%) compared with eligible dosage criteria (n=39,097). Conclusions Rivaroxaban dosing regimen following J-ROCKET criteria may serve as an alternative to ROCKET-AF criteria for the Asian population with NVAF, whereas the dosing regimen following ROCKET AF criteria was more favorable for the non-Asian population. Off-label underdosed rivaroxaban 10mg was associated with a higher risk of thromboembolism but a lower risk of major bleeding, while off-label overdosed rivaroxaban 20mg was associated with worse outcome in most clinical events.

Iron status and the Pi/FGF-23-axis in HFrEF in relation to renal function

Abstract Background Recent studies linked dysregulated phosphate metabolism, fibroblast growth factor-23 (FGF-23) and iron deficiency (ID) with worse clinical outcome and mortality in heart failure with reduced ejection fraction (HFrEF). These factors are intertwined as FGF-23 regulates inorganic phosphate (Pi) through increased renal phosphate secretion and is stimulated by elevated Pi levels and ID. This interplay has recently gained attention as intravenous iron supplementation has hypophosphataemia as a side effect. The relationship between ID and the Pi/FGF-23-axis, particularly concerning renal function, has not been investigated in detail. Purpose We aimed to evaluate the relationship between iron status, Pi and FGF-23 in relation to renal function in HFrEF. Methods Stable HFrEF patients were enrolled at our outpatient clinic between 2018 and 2023 in a prospective registry. Baseline characteristics, medications and laboratory values were documented. For this study patients with complete phosphate, intact FGF-23 and iron status were analyzed (n = 429). Patients were divided into three groups based on their renal function determined by estimated glomerular filtration rate (GFR): GFR > 60, GFR 60-30, GFR < 30. Results The median age was 65 (IQR 52-74), 310 (72%) patients were male, median NT-proBNP was 1657 pg/ml (IQR 512-4116) and median GFR was 57 ml/min/BSA (IQR 37-74). Of the 429 patients, 180 (42%) suffered from ID. Pi levels did not vary based on NYHA stage and showed only a weak correlation with NT-proBNP (r = 0.13, p = 0.008). In contrast, FGF-23 increased with NYHA stage (NYHA I vs NYHA II vs NYHA III/IV: 69.9 (IQR 50-90.2) vs 82.4 (IQR 58.9-115.8) vs 104.2 (IQR 77-199.5), p<0,0001) and correlated positively with NT-proBNP (r = 0.43, p<0.0001) (Figure 1 a, b). Patients with a GFR < 30ml/min/BSA had significantly higher concentrations of Pi and FGF-23 compared to GFR 30-60 ml/min/BSA or > 60ml/min/BSA [Pi: 1.36 mmol/l (IQR 1.15-1.61) vs 1.145 mmol/l (IQR 0.96-1.27) vs 1.1 mmol/l (IQR 0.98-1.25), p<0.0001; FGF-23: 253.1 pg/ml (141.1-936.2) vs 94.3 pg/ml (IQR 75.43-121.5) vs 71.7 pg/ml (IQR 53.18-89.33), p<0.0001)] (Figure 1 c, d). While there was no difference regarding mortality according to Pi levels, patients in the highest FGF-23 tertile had excess mortality (p=ns and p = 0.0002, log rank test) (Figure 1 e). Interestingly, Pi and FGF-23 levels did not differ between patients without and with ID (p=ns for both, Figure 2 a). No correlation could be shown between transferrin saturation and Pi or FGF-23 (p=ns, Figure 2 b). Conclusion The regulation of Pi and FGF-23 is dependent on renal function. Patients with a GFR < 30ml/min/BSA exhibited the highest levels of both FGF-23 and Pi. The phosphaturic effect of FGF-23 seems to rely on renal function, as elevated FGF-23 cannot sufficiently decrease Pi in patients with a GFR < 30ml/min/BSA. No correlation between iron status and FGF23/Pi could be identified for HFrEF.Figure 1Figure 2

Prevalence of atrial fibrillation in patients with atrial septal defect and its impact on in-hospital outcomes

Abstract Background Atrial septal defect (ASD) is one of the most common congenital heart diseases in adulthood. ASDs have left-to-right shunt and primarily right-sided volume overload. This leads to electrical remodeling that may predispose patients to atrial fibrillation (AF). There is limited data on the impact of AF on clinical outcomes in patients with ASD. Purpose To study the prevalence of AF and its impact on in-hospital outcomes in adult patients with ASD. Methods This is a retrospective cohort analysis of all ASD related hospitalizations between January 1, 2016, and December 31, 2020, from the National Inpatient Sample, the largest publicly available all-payer inpatient care database in the United States. Our study population included adult patients (≥ 18 years) with ASD using ICD-10 diagnostic codes. Patients with a diagnosis of acquired ASD were excluded. ASD patients were divided into two groups: with and without AF. We used Chi square test for categorical variables and t-test for continuous variables to compare group differences between ASD with AF and ASD without AF. Univariate and multivariate logistic regression were used to analyze the clinical outcomes between the two groups. Results From 2016 to 2020, we identified 82,574 hospitalizations with primary diagnosis of ASD, of which 23,907 (29%) had coexisting AF. The mean age was 71 years. Among them, 48% were female. Racial distributions were: 81% Whites, 8.8% Blacks, 5.9% Hispanics and 2.1% Asians. Compared to ASD without AF, ASD with AF hospitalizations were older in age (mean age: 71 vs 59, p<0.001), had higher prevalence of chronic heart failure (56% vs 25%, p<0.001), hypertension (71% vs 61%, p<0.001), obstructive sleep apnea (16% vs 9%, p<0.001), and higher Charlson comorbidity index (CCI) of ≥3 (52% vs 46%, p<0.001). ASD patients with AF had higher in-hospital mortality (aOR: 1.25, 95% CI: 1.14, 1.37, p<0.001), longer length of stay (beta coefficient: 0.15, 95% CI 0.13, 0.17, p<0.001), higher odds of acute heart failure (aOR:3, 95% CI: 2.86, 3.15, p<0.001), cardiogenic shock (aOR: 2.68, 95% CI: 2.42, 2.97, p<0.001), acute kidney injury (aOR:1.4, 95% CI: 1.35, 1.46, p<0.001) and requirement of permanent pacemaker (PPM) (aOR: 2.51, 95% CI: 2.16, 2.92, p<0.001) compared to ASD without AF after controlling for age, race, CCI, obesity, COPD and pulmonary hypertension. Conclusions Our study showed that a significant percentage of hospitalized patients with ASD had concomitant AF. AF can contribute to higher in-hospital mortality and worse clinical outcomes in patients with ASD. This highlights the importance of optimal management of AF in patients with ASD.

Abstract 17257: Aortopulmonary Collateral Burden in the Fontan Circulation: Longitudinal Changes and Relationship With Clinical Outcomes

Background: Aortopulmonary collaterals (APC) are a common source of volume load in patients with a Fontan circulation and their burden can be quantified by CMR. Longitudinal trends in APC flow and their relationship with outcomes have not been described. Hypothesis: Higher APC flow will be associated with worse clinical outcomes in Fontan patients. Aims: To assess longitudinal changes in APC flow in the Fontan circulation using CMR and their relationship with outcomes. Methods: Single-center retrospective analysis of Fontan patients who had at least 1 CMR with APC flow data. APC flow was estimated as the difference between aortic and systemic venous flows and also expressed as a percent of aortic flow. Primary outcome was a composite of death or heart transplantation; secondary outcomes included protein losing enteropathy, ascites, chylothorax, and hemoptysis. The baseline (time at Fontan=time 0) and trend in APC flow were estimated using a linear mixed model with a random intercept and slope for each patient. Results: Analysis included 758 CMRs from 356 patients; 123 of whom had ≥ 2 CMRs. Median age at first CMR was 14 y (IQR 10-19 y) and median CMRs per patient were 2 (range 1-12). Baseline APC flow was 0.6 (±0.5) L/min/m 2 or 17 (±10) % of aortic flow. Increasing APC flow over time correlated with increasing trend in ventricular dilation and decreasing trend in SaO 2 . Over a median follow-up of 17 years, 22 patients (6%) had the composite outcome. High baseline APC flow as well as an increasing trend in APC flow were associated with clinical outcomes including an independent association with death or heart transplantation (Table). Conclusions: APCs represent a significant hemodynamic burden in functional single ventricle hearts palliated to the Fontan circulation. Higher and increasing APC flow is associated with worse clinical outcomes. Factors contributing to APC development and whether APC occlusion results in a lasting reduction in the burden remain to be elucidated.

Abstract 16828: Plaque Rupture is Not Associated With Worse Clinical Outcomes in Contemporary Patients With Acute Coronary Syndrome

Introduction: The worse clinical outcomes in patients with plaque rupture (PR) than those with other pathogenesis of acute coronary syndrome (ACS) including plaque erosion and calcified plaque-related ACS have been reported. Hypothesis: The incidence of recurrent adverse events in patients with PR is not higher than other ACS patients in the contemporary clinical setting of secondary prevention using high-intensity statin. Methods: A total of 329 consecutive patients with ACS who underwent optical coherence tomography imaging of culprit lesions were included. Patients were classified into either the PR group (n = 133) or the non-PR group (n = 196). The incidence of major adverse cardiovascular events (MACE) at 1-year was compared between the two groups. MACE included cardiac death, non-fatal myocardial infarction, target vessel revascularization (TVR), and non-TVR. Results: The prevalence of ST-elevation myocardial infarction (STEMI) as the initial clinical presentation was significantly higher in the PR group than in the non-PR group (58.6 vs. 42.3 %, p = 0.005). The prescription rate of high-intensity statin and/or ezetimibe at discharge was comparable in the two groups (84.2 vs. 84.7 %, p = 1.000). The incidence of MACE at 1-year was significantly lower in the PR group than in the non-PR group (log-rank p = 0.009) (Panel A). In the non-PR group, the levels of body mass index (26.5 ± 2.9 vs. 24.0 ± 3.9 kg/m 2 , p = 0.004) and hemoglobin A1c (7.2 ± 2.5 vs. 6.4 ± 1.2 %, p = 0.021) were significantly higher in patients with MACE than in those without (Panel B). Conclusions: The incidence of MACE at 1-year in patients with PR was significantly lower than in those without PR in contemporary patients with ACS despite of the higher prevalence of baseline STEMI presentation. Further tailored optimization of secondary prevention against obesity and diabetes may be still required in ACS patients without PR.

Abstract 13078: Prognostic Significance of Reticulocyte Production Ability in Patients With Chronic Heart Failure

Background: Anemia is frequently observed in patients with chronic heart failure (CHF), and many studies have evaluated the association between anemia and mortality in CHF. The quality of erythropoiesis is an intrinsic aspect of pathophysiology of anemia, and the ability of reticulocyte production would be one of the pivotal factors in the quality of erythropoiesis. However, it remains unclear whether reticulocyte production ability is associated with clinical outcomes in patients with CHF. Methods: We prospectively examined 1,274 symptomatic CHF patients (mean age 71.9±13.4 years, median LVEF 50 [IQR 36-63]%) in a multicenter registry (25 sites). The reticulocyte production ability was evaluated by calculating the reticulocyte production index (RPI) using reticulocyte counts and serum hematocrit. Patients were divided into four groups according to the presence of WHO defined anemia and the median value of RPI. The primary outcome was composite of all-cause death and hospitalization for worsening HF. Results: During a median follow-up period of 427 (IQR 273-642) days, the primary outcome occurred in 222 (17%) patients. The group with anemia and high RPI (≥0.982, the median) showed the highest incidence of the primary outcome among the groups ( P < 0.001) (Figure A). In an anemic subgroup (n = 611), higher RPI was independently associated with increased adverse events (HR 1.67, 95% CI 1.31-2.13) adjusted for age, sex, estimated glomerular filtration rate, NT-pro BNP, hemoglobin, serum sodium and iron parameters. In this subgroup, erythrocyte counts were not significantly increased in patients with higher RPI compared to lower RPI (Figure B). Moreover, there were no significant differences on transferrin saturation and serum iron between the groups (Figure B). Conclusions: Higher reticulocyte production ability, which might reflect the impaired process of erythropoiesis, was associated with worse clinical outcomes in patients with CHF, especially with anemia.

Abstract 14035: Clinical Outcomes Following Hospitalization for COVID-19 in Patients With Cardiac Sarcoidosis in the United States

Background: Chronic immunosuppressive therapy and concomitant pulmonary involvement are two possible factors that could contribute towards adverse outcomes for patients with a history of Cardiac Sarcoidosis (CS) who are hospitalised with Covid-19. In this study, we aimed to identify co-morbidities and clinical outcomes for patients with CS post hospitalization for Covid-19. Methods: Patients aged ≥18 years, with a positive diagnosis of COVID-19 (via ICD-10 code “U071”) between 1st April 2020 to 31st December 2020, were identified from National Inpatient Sample Database. Patients with CS were compared for patient characteristics, demographics and hospital-related outcomes against patients without CS using multivariable regression analysis. Results: We identified a total of 1,608,285 cases of COVID-19 infection admitted to the hospital out of whom 60 patients were confirmed to have CS. CS patients were younger (mean 57.8 vs. 63.3 years, p<0.01), had a higher mean Charlson comorbidity index (CCI: 5.17 vs. 2.72, p<0.01) with greater prevalence of previous myocardial infarction (25.0% vs. 4.2%, p<0.01), atrial fibrillation (58.3% vs. 15.6%, p<0.01), smoking (50% vs. 26.1%, p<0.01), chronic kidney disease (66.7% vs. 20.6%, p<0.01) and diabetes (75.0% vs. 40.0%, p<0.01) as compared to patients without CS. Moreover, clinical outcomes of patients with CS were more adverse following hospitalization for COVID-19 including use of mechanical ventilation (25.0% vs. 11.2%, p<0.01, adjusted OR 1.39 95% CI: 1.37-1.41), acute kidney injury (50.0% vs. 28.2%, p<0.01, adjusted OR 1.86, 95% CI: 1.84-1.88) and death (25.0% vs. 13.1%, p<0.01, adjusted OR 3.15, 95% CI: 3.10- 3.20) (Table 1). Conclusion: CS patients hospitalized for COVID- 19 infection had greater CCI and worse clinical outcomes such as mechanical ventilation use, acute kidney injury and death when compared to patients without cardiac sarcoidosis. Keywords: Cardiac sarcoidosis, COVID- 19, outcomes.