Incidence Of Clinical Events Research Articles

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: implications of insulin treatment: a report from the GLORIA-AF Registry Phase III

Abstract Background Atrial Fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations has not been fully elucidated, especially in relation to insulin use. Purpose To analyze the associations between DM and the risk of clinical adverse events in patients with AF, and second, explore the impact of insulin treatment in these patients. Methods We studied patients with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-years follow-up. Clinical events included all-cause death, major bleeding, myocardial infarction (MI), stroke, thromboembolism (TE), and major adverse cardiovascular events (MACE). MACE was defined as a composite of stroke, MI and major bleeding. Kaplan-Meier curves were used to estimate the cumulative incidence of clinical events. Multivariable cox regression models with subgroups were used to estimate the association between DM and the risk of mortality and clinical events. Results A total of 15,861 AF patients were included (mean age 70.00 ± 10,21 years old; 55% male, 20% Asia), of which 3,666 had DM (mean age 70.04 ± 9.54 years old; 59% male, 21% Asia). Kaplan-Meier curves showed that AF patients with DM had higher cumulative hazard of all outcomes, including all-cause death (OR: 1.56, 95%CI: 1.38-1.77), CVD (OR: 1.72, 95%CI: 1.44-2.06), major bleeding (OR: 1.4, 95%CI: 1.17-1.67), stroke (OR: 1.29, 95%CI: 1.04-1.61), TE (OR: 1.26, 95%CI:1.02-1.56), MI (OR: 1.88, 95%CI: 1.48-2.39) and MACE (OR: 1.61, 95%CI: 1.41-1.84). After adjustment by prior disease and drugs, the outcomes of stroke (OR: 1.19, 95%CI: 0.95-1.49) and TE (OR: 1.22, 95%CI: 0.98-1.52) showed not significant. Subgroup analysis found that increased risks of stroke were found in female (OR: 1.43, 95%CI: 1.03-1.98, Pinteraction = 0.062) and non-Asian patients (OR: 1.39, 95%CI: 1.06-1.82, Pinteraction = 0.175) with DM. For all cause death, subgroup results were similar with overall patients. In addition, insulin use increased the risk of all cause death (OR: 1.82, 95%CI: 1.45-2.29), CVD (OR: 1.70, 95%CI: 1.22-2.37), major bleeding (OR: 1.54, 95%CI: 1.08-2.18), MI (OR: 1.72, 95%CI: 1.12-2.64), MACE (OR: 1.65, 95%CI: 1.28-2.11) in patients with AF and DM. Multivariable model showed similar result. Conclusions DM was independently associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF. Insulin use was associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF and DM.Figure 1Figure 2

A comprehensive assessment tool of acute-phase rehabilitation is associated with clinical outcomes in patients after cardiovascular surgery.

Perme intensive care unit (ICU) mobility score is a comprehensive mobility assessment tool; however, its usefulness and validity for patients after cardiovascular surgery remain unclear. We investigated the association between the Perme Score and clinical outcomes after cardiovascular surgery. We retrospectively enrolled 249 consecutive patients admitted to the ICU after cardiac and/or major vascular surgery. The Perme Score contains categories on mental status, potential mobility barriers, muscle strength and mobility level and was assessed within 2days after surgery. The outcomes of physical recovery were the number of days until 100-m ambulation achievement and 6-min walk distance (6MWD) at hospital discharge. The endpoint was a composite outcome of all-cause mortality and/or all-cause unplanned readmission. We analyzed the associations of the Perme Score with physical recovery and the incidence of clinical events. After adjusting for clinical confounding factors, a higher Perme Score was an independent factor of earlier achievement of 100-m ambulation (hazard ratio: 1.039, 95% confidence interval [CI]: 1.012-1.066) and higher 6MWD (β: 0.293, P = .001). During the median follow-up period of 1.1years, we observed an incidence rate of 19.4/100 person-years. In the multivariate Poisson regression analysis, a higher Perme Score was significantly and independently associated with lower rates of all-cause death/readmission (incident rate ratio: 0.961, 95% CI: 0.930-0.992). The Perme Score within 2days after cardiovascular surgery was associated with physical recovery during hospitalization and clinical events after discharge. Thus, it may be useful for predicting clinical outcomes.

Benefits of dapagliflozin in chronic kidney disease for US commercial payers: A cost-offset analysis.

One in 7 adults have chronic kidney disease (CKD), which is associated with high morbidity and mortality and substantial health care costs, especially in more advanced disease. Our data from a US commercial payer show rising per-member-per-year costs for renal and cardiac complications associated with CKD. To predict the clinical and economic impact of treatment with or without dapagliflozin from the perspective of a US commercial payer using a cost-offset model (COM). The COM used real-world cost and member count data from a US employer-sponsored commercial payer and results of the double-blind, randomized, phase 3 Dapagliflozin and Prevention of Adverse Outcomes in CKD clinical trial (NCT03036150) to predict the incidence of clinical events, including a greater than or equal to 50% decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, and hospitalization for heart failure, and their associated costs over a 3-year period. The COM compared a hypothetical scenario of the experience with or without dapagliflozin in members with CKD stages 2-4, aged younger than 65 years. In the simulated populations of 130 members, the COM projected 9 events of a greater than or equal to 50% decline in estimated glomerular filtration rate for the experience with dapagliflozin vs 15 events for the experience without dapagliflozin (6 fewer events; number needed to treat [NNT] = 20, amounting to estimated cumulative cost offsets of $0.57 million [M] over a 3-year period). The COM projected similar results for end-stage kidney disease (8 events with dapagliflozin vs 14 events without dapagliflozin; NNT = 24, amounting to $1.92 M in cumulative cost offsets) and for hospitalization for heart failure (13 events with dapagliflozin vs 33 events without dapagliflozin; NNT = 7, amounting to $0.79 M in cumulative cost offsets). These projections translated to total mean, cumulative cost offsets of $3.89 M for all clinical events evaluated over the 3-year period (36.6% reduction with dapagliflozin vs without dapagliflozin), and net mean, cumulative cost offsets of $2.58 M over the 3-year period (24.2% reduction with dapagliflozin vs without dapagliflozin) after factoring in a discounted wholesale acquisition cost for dapagliflozin expenditure ($1.31 M over 3 years). Thus, the net mean, cumulative cost offsets were $19,843 per member over 3 years, representing a 197% return on investment for dapagliflozin expenditure. Results of our COM suggest that dapagliflozin can reduce clinical events and their associated costs over a 3-year period when compared with a scenario without dapagliflozin. Cost offsets increased with each year, indicating that US commercial payers can substantially reduce costs associated with CKD morbidity and mortality.

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Novo Nordisk.

Quantitative flow ratio or angiography for the assessment of non-culprit lesions in acute coronary syndromes, a randomized trial.

Patients undergoing percutaneous coronary intervention for acute coronary syndromes often have multivessel disease (MVD). Quantitative flow ratio (QFR) is an angiography-based technology that may help quantify the functional significance of non-culprit lesions, with the advantage that measurements are possible also once the patient is discharged from the catheterization laboratory. Our two-center, randomized superiority trial aimed to test whether QFR, as compared to angiography, modifies the rate of non-culprit lesion interventions (primary functional endpoint) and improves the outcomes of patients with acute coronary syndromes and MVD (primary clinical endpoint). In total, 202 consecutive patients (64 [56-71] years of age, 160 men) with STEMI (n = 69 (34%)), NSTEMI (n = 94 (47%)), or unstable angina (n = 39 (19%)) and MVD who had undergone successful treatment of all culprit lesions were randomized 1:1 to angiography- vs. QFR-guided delayed revascularization of 246 non-culprit stenoses (1.2/patient). The proportion of patients assigned to medical treatment versus percutaneous intervention was not different between groups (angiography group: 45 (45%) vs. QFR: 56 (55%), P = 0.125; relative risk = 0.80 (0.60-1.06)). At 12months, a primary clinical endpoint event (composite of death, nonfatal myocardial infarction, revascularization, and significant angina) occurred in 24 patients (angiography-guided) and 23 patients (QFR-guided; P = 0.637, HR = 1.16 [0.63-2.15]). None of its components was different between groups. QFR guidance based on analysis of images from the primary intervention was not associated with a difference in the rate of non-culprit lesion staged revascularization nor in the 12-month incidence of clinical events in patients with acute coronary syndromes and multivessel disease. ClinicalTrials.gov Registry (NCT04808310).

Cost Offset of Dapagliflozin in the US Medicare Population with Cardio-Kidney Metabolic Syndrome.

Cardiovascular-kidney-metabolic (CKM) syndrome is highly prevalent in the US Medicare population and is projected to increase further. Sodium-glucose co-transporter2 inhibitors have indications in chronic kidney disease (CKD), heart failure (HF), and type2 diabetes (T2D), providing protective efficacy across conditions within CKM syndrome. The objective of this study was to develop a model to extrapolate key outcomes observed in pivotal clinical trials to the US Medicare population, and to assess the potential direct cost offsets associated with dapagliflozin therapy. All US 2022 Medicare beneficiaries (≥ 65years of age) eligible to receive dapagliflozin were estimated according to drug label indication and Medicare enrollment and claims data. Incidence of key outcomes from the dapagliflozin clinical program were modelled over a 4-year time horizon based on patient-level data with CKD, HF, and T2D. Published cost data of relevant clinical outcomes were used to calculate direct medical care cost-offset associated with treatment with dapagliflozin. In a population of 13.1million patients with CKM syndrome, treatment with dapagliflozin in addition to historical standard of care (hSoC) versus hSoC alone led to fewer incidents of HF-related events (hospitalization for HF, 613,545; urgent HF visit, 98,896), renal events (kidney failure, 285,041; ≥ 50% sustained decline in kidney function, 375,137), and 450,355fewer deaths (of which 225,346 and 13,206 incidences of cardiovascular and renal death were avoided). In total this led to medical care cost offsets of $99.3billion versus treatment with hSoC only (dapagliflozin plus hSoC, $310.3billion; hSoC, $211.0billion). By extrapolating data from trials across multiple indications within CKM syndrome, this broader perspective shows that considerable medical care cost offsets may result through attenuated incidence of clinical events in CKD, T2D, and HF populations if treated with dapagliflozin in addition to hSoC over a 4-year time horizon. Graphical abstract available for this article.

Evaluación de eventos clínicos y costes asociados a la adición de dapagliflozina al tratamiento de la enfermedad renal crónica: análisis de compensación de costes

Background and objectivesChronic kidney disease (CKD) is a serious health problem with an increasing clinical, social and economic impact in advanced stages. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor that reduces the risk of CKD progression, in addition to provide cardiovascular benefits and reduce all-cause mortality. The aim of this study was to determine the short-term clinical and economic impact of dapagliflozin as an add-on to renin-angiotensin-aldosterone system inhibitors (RAASi) standard therapy for CKD in Spain. Materials and methodsA cost-offset model was used to compare the costs of clinical events and pharmacological per 100,000 CKD patients in a virtual cohort treated with dapagliflozin added to RAASi standard therapy versus RAASi standard therapy alone. Renal (progression to renal failure and acute kidney injury), cardiovascular (hospitalisation for heart failure [HF]), and all-cause mortality events were assessed. The incidence of clinical events by treatment arm was obtained from the DAPA-CKD study, and costs were obtained from national databases and the literature. ResultsOver 3 years, treatment with dapagliflozin would reduce progression to renal failure (−33%; 7,221 vs. 10,767), hospitalisation for HF (−49%; 2,370 vs. 4,683) and acute kidney injury (−29%; 4,110 vs. 5,819). The savings associated with this reduction in events was €258 million per 100,000 patients, of which 63.4% is due to the avoidance of dialysis for renal failure. Considering the event and pharmacological treatment costs, the total net savings were estimated at €158 million per 100,000 patients. ConclusionsDelaying progression of CKD and reducing the incidence of clinical events thanks to the treatment with dapagliflozin could generate savings for the Spanish National Health System, even when pharmacological costs are taken into account.

Impact of the number of modifiable risk factors on clinical outcomes after percutaneous coronary intervention: An analysis from the e-Ultimaster registry

AimsA substantial proportion of the patients undergoing percutaneous coronary intervention (PCI) have none of the of standard modifiable cardiovascular risk factors (SMuRFs): hypertension, diabetes, hypercholesterolaemia and smoking. The aim of this analysis was to compare clinical outcomes after PCI according to the number of SMuRFs. MethodsPatients with an indication for a PCI were stratified based upon the number of SMuRFs: 0, 1, 2 or 3–4. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction or clinically driven target lesion revascularization at 1-year. Inverse weighted propensity score (IWPS) adjustment was performed to adjust for differences in baseline characteristics. ResultsThe prevalence of SMuRFs was: 0 SMuRF 16.4 %; 1 SMuRF 27.8 %; 2 SMuRFs 34.7 % and 3–4 SMuRFs 21.1 %. Patients without SMuRFs were younger, more likely to be male and had less complex coronary artery disease. The incidence of TLF increased with the number of SMuRFs: 2.65 %, 2.75 %, 3.23 %, and 4.24 %, Ptrend < 0.001. The relative risk (RR) for a TLF was 60 % higher (95 % confidence interval 1.32–1.93, p < 0.01) for patients with 3–4 SMuRFs compared to patients without SMuRFs. The trend remained (Ptrend < 0.01) after IWPS with TLF rates of 2.88 %, 2.64 %, 2.88 % and 3.65 %. The RR for a TLF was 27 % higher (95 % CI 1.05–1.53, p < 0.01). ConclusionThe incidence of clinical events at 1-year increased with the number of SMuRFs. While patients without SMuRFs have a relatively favourable risk profile, more research is needed to optimize therapeutic management in the majority of patients.

Clinical, laboratory, and molecular characteristics of a cohort of children with hemoglobinopathy S/beta-thalassemia

IntroductionHemoglobinopathy Sβ-thalassemia (HbSβ-thal) has a wide range of clinical and laboratory severity. There is limited information on the natural history of HbSβ-thal and its modulating factors. We described the molecular, hematological, and clinical characteristics of a cohort of children with HbSβ-thal and estimated its incidence in Minas Gerais, Brazil. MethodsLaboratory and clinical data were retrieved from medical records. Molecular analysis was performed by HBB gene sequencing, PCR-RFLP, gap-PCR, and MLPA. ResultsEighty-nine children were included in the study. Fourteen alleles of β-thal mutations were identified. The incidence of HbSβ-thal in the state was 1 per 22,250 newborns. The most common βS-haplotypes were CAR and Benin. The most frequent βthal-haplotypes were V, II, and I. Coexistence of 3.7 kb HBA1/HBA2 deletion was present in 21.3 % of children. β-thalassemia mutations were associated with several clinical and laboratory features. In general, the incidence of clinical events per 100 patient-years was similar for children with HbSβ0-thal, IVS-I-5 G>A, and IVS-I-110 G>A. Children with HbSβ+-intermediate phenotypes had a more severe laboratory and clinical profile when compared with those with HbSβ+-mild ones. βS-haplotypes and α-thalassemia did not meaningfully influence the phenotype of children with HbSβ-thal. ConclusionThe early identification of β-thalassemia alleles may help the clinical management of these children.

Long-term benefits of drug-coated balloons for coronary artery revascularization.

Percutaneous coronary intervention (PCI) with drug-eluting stents (DES) represents the treatment of choice for the majority of patients with coronary artery disease. While currently available DES, in addition to physiological support, has failed to show the non-inferiority to coronary artery bypass grafting (CABG) in terms of cumulative incidence of clinical events over the short-term follow-up. Studies have also shown that DES is associated with an increased risk of target vessel revascularization compared to CABG after long-term follow-up. Drug-coated balloons (DCB) have been shown to provide clinically significant benefits in the management of in-stent restenosis and diffuse coronary artery disease, as well as small coronary artery lesions. The aim of this review was to describe the inherent technical limitations of DES and highlight the potential advantages of PCI with DCB for long-term outcomes and potentially demonstrate its non-inferiority to CABG. Currently, ongoing studies will provide more information and help to understand if a blended therapy of DCB+DES can match the performance of CABG in the need for revascularization in more complex patients.

Impact of Preprocedural Frailty Status in Elderly Transvenous Pacemaker Recipients.

The number of TV-PM implantations in elderly people is increasing. Although frailty syndrome is common in elderly patients, the relationship between the pre-procedural frailty status and clinical outcomes has not been fully elucidated in elderly TV-PM recipients.This study included 103 consecutive patients over 80 years old who were newly implanted with a TV-PM (age 85.7 ± 4.2, 41.7% male). We assessed the relationship between the clinical outcome and predictive factors, especially for the pre-procedural frailty status after the TV-PM implantation. The pre-procedural frailty status was retrospectively assessed from the medical records and classified on the basis of impairments in 3 domains (walking, cognition, and activities of daily living). The primary endpoint was defined as a heart failure admission.During the follow-up period (4.1 ± 2.3 years), 20 patients (19.4%) met the primary endpoint. Frailty syndrome was identified in 40 patients (38.8%). In univariate analysis, the LVEF (HR 0.97, 95% CI 0.96-1.00 P = 0.0492), an RV pacing burden over 40% (HR 1.58, 95% CI 1.00-2.54 P = 0.0473), and presence of a frailty status (HR 1.82, 95% CI 1.13-2.87 P = 0.0134) were found to be statistically significant predictors for the study endpoint. In multivariate analysis, having frailty syndrome was the only predictive factor for a heart failure admission (HR 1.83, 95% CI 1.12-2.93 P = 0.0157).The presence of frailty syndrome and incidence of clinical events were high and a pre-procedural frailty status assessment was key in determining the clinical outcomes in TV-PM recipients over 80 years old.

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.

Abstract 13820: Association of Cardiothoracic Ratio With Heart Failure Events in Atrial Fibrillation Without Heart Failure: The Fushimi AF Registry

Background: The cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess cardiac volume status. We previously reported that N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was associated with higher incidence of clinical events in patients with atrial fibrillation (AF) without pre-existing heart failure (HF). However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF events in AF patients without HF. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. After excluding patients with pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%), we divided 1,049 patients into four groups according to their CTR and NT-proBNP level (median value: 495 ng/L) at baseline, and compared the incidence of HF events (composite of cardiac death or HF hospitalization) among the groups; G1 (Lower CTR&lt;50% and Lower NT-proBNP&lt;495, n=256), G2 (Higher CTR≥50% and Lower NT-proBNP&lt;495, n=268), G3 (Lower CTR&lt;50% and Higher NT-proBNP≥495, n=117) and G4 (Higher CTR≥50% and Higher NT-proBNP≥495, n=408). Results: During the median follow-up of 5.4 years, the incidence rates of HF events in the groups either having higher NT-pro BNP group or higher CTR group were higher, as compared with patients with lower CTR and lower NT-proBNP (G1: 0.5% per person-year, G2: 1.3%, G3: 1.6% and G4: 2.5%; p&lt;0.01) (Figure). Multivariate Cox regression analysis revealed that higher CTR (≥50%) was independently associated with the incidence of HF events in AF patients without prior HF hospitalization (hazard ratio: 1.47, 95% confidence interval: 1.09-2.00). Conclusion: In Japanese AF patients without pre-existing HF, higher CTR was associated with higher incidence of HF events irrespective of NT-proBNP level.

Estimating the impact of single pill combination therapy for hypertension: projections of patient outcomes in Italy.

Hypertension affects almost a third of the Italian population and is a major risk factor for cardiovascular disease. Management of hypertension is often hindered by poor adherence to complex treatment regimens. This analysis aimed to estimate the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with other treatment pathways for the management of hypertension in Italy. A microsimulation modeling approach was used to project health outcomes over a 10-year period for people with hypertension. Input data for four treatment pathways [current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and SPC] were sourced from the Global Burden of Disease 2017 data set. The model simulated clinical outcomes for 1 000 000 individuals in each treatment pathway, including mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD) and disability-adjusted life years (DALYs). Through improved adherence, SPC was projected to improve clinical outcomes versus CTP, SLGS, and FCC. SPC was associated with reductions in mortality, incidence of clinical events, and DALYs versus CTP of 5.4%, 11.5%, and 5.7%, respectively. SLGS and FCC were associated with improvements in clinical outcomes versus CTP, but smaller improvements than those associated with SPC. Over 10 years, combination therapies (including SPC and FCC) were projected to reduce the burden of hypertension compared with conventional management approaches in Italy. Due to higher adherence, SPC was associated with the greatest overall benefits versus other regimens.

A novel biodegradable polymer-coated sirolimus-eluting stent: the 1-year results of the HELIOS registry.

The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting. The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves. A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54%-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year. The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence of the HELIOS stent for the evaluation of Interventional Cardiologists and Policymakers. ClinicalTrials.gov, NCT03916432.

Comparison of thrombotic and clinical outcomes in SARS-CoV-2-pneumonia versus other viral pneumonia in an urban academic medical center

BackgroundInfection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations. ObjectivesAssess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia. MethodsRetrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding. ResultsOf 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not. ConclusionLow overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

Long Term Follow-Up of Patients with Systemic Right Ventricle and Biventricular Physiology: A Single Centre Experience.

A progressively increasing prevalence of congenital heart disease (CHD) in adulthood has been noticed in recent decades; CHD cases with a systemic right ventricle have a poorer outcome. Seventy-three patients with SRV evaluated in an outpatient clinic between 2014 and 2020 were enrolled in this study. Thirty-four patients had a transposition of the great arteries treated with an atrial switch operation; 39 patients had a congenitally corrected transposition of the great arteries (ccTGA). Mean age at the first evaluation was 29.6 ± 14.2 years; 48% of the patients were female. The NYHA class at the visit was III or IV in 14% of the cases. Thirteen patients had at least one previous pregnancy. In 25% of the cases, complications occurred during pregnancy. Survival free from adverse events was 98.6% at one year and 90% at 6-year follow-up without any difference between the two groups. Two patients died and one received heart transplantation during follow-up. The most common adverse event during follow-up was the presence of arrhythmia requiring hospitalization (27.1%), followed by heart failure (12.3%). The presence of LGE together with lower exercise capacity, higher NYHA class and more dilated and/or hypokinetic RV predicted a poorer outcome. Quality of life was similar to the QoL of the Italian population. Long-term follow-up of patients with a systemic right ventricle is characterized by a high incidence of clinical events, prevalently arrhythmias and heart failure, which cause most of the unscheduled hospitalizations.

Prevalence of multimorbidity and its associations with hospitalisation or death in Japan 2014–2019: a retrospective cohort study using nationwide medical claims data in the middle-aged generation

ObjectiveTo describe the prevalence of multimorbidity and its associations with clinical outcomes across age groups.DesignRetrospective cohort study using nationwide medical claims data.SettingCarried out in Japan between April 2014 and March...

Morbidity and mortality after anesthesia in early life in Italy. A subgroup analysis of the NECTARINE Trial.

Recent literature on neonatal anesthesia focuses on the importance of keeping physiology within the ranges of normality to improve the long-term neurological outcome. The Neonate and Children audit of Anesthesia pRactice IN Europe (NECTARINE) showed a derangement of one or more than one physiological parameters during anesthesia needing a medical intervention in 35.2% of 6592 anesthesia procedure performed in infants up to 60 weeks postmenstrual age. Subanalysis of the Italian NECTARINE cohort providing a snapshot of anesthesia management, incidence of clinical events requiring intervention during anesthesia, and morbidity and mortality at 30 and 90 days. Secondary aim was to compare outcomes between Italy and Europe. Twenty-three Italian centers recruited 501 patients (63% male, 37% female) undergoing 611 procedures (441 surgical and 170 non-surgical) with a mean gestational age at birth of 38 weeks. Events requiring a medical intervention during anesthesia occurred in 177 cases (28.9%), lower than those reported in Europe (35.3%). The majority of events concerned episodes of cardiovascular instability, most commonly due to hypotension. The incidence of mortality at 30 days was 2.7%, consistent with the European incidence. Anesthetizing neonates is challenging. It is crucial that neonatal anesthesia practice is performed in specialized centers to maximize the potential positive outcome. We recommend a certification of quality for Institutions providing care for very young patients.

Six-months clinical and intracoronary imaging follow-up after reverse T and protrusion or double-kissing and crush stenting for the treatment of complex left main bifurcation lesions.

There is a debate regarding the best stent strategy for unprotected distal left main (LM) bifurcation disease. Among two-stent techniques, double-kissing and crush (DKC) is favored in current guidelines but is complex and requires expertise. Reverse T and Protrusion (rTAP) was shown to be a comparable strategy regarding short-term efficacy and safety, but with reduced procedural complexity. To compare rTAP vs. DKC by optical coherence tomography (OCT) on the intermediate term. 52 consecutive patients with complex unprotected LM stenoses (Medina 0,1,1 or 1,1,1) were randomized to either DKC or rTAP and followed-up for a median of 189[180-263] days for clinical and OCT outcomes. At follow-up OCT showed similar change in the side branch (SB) ostial area (primary endpoint). The confluence polygon showed a higher percentage of malapposed stent struts in the rTAP group that did not reach statistical significance (rTAP: 9.7[4.4-18.3] % vs. DKC: 3[0.07-10.9] %; p = 0.064). It also showed a trend towards larger neointimal area relative to the stent area (DKC: 8.8 [6.9 to 13.4] % vs. rTAP: 6.5 [3.9 to 8.9] %; p = 0.07), and smaller luminal area (DKC: 9.54[8.09-11.07] mm2 vs. rTAP: 11.21[9.53-12.42] mm²; p = 0.09) in the DKC group. The minimum luminal area in the parent vessel distal to the bifurcation was significantly smaller in the DKC group (DKC: 4.64 [3.64 to 5.34] mm² vs. rTAP: 6.76 [5.20 to 7.29] mm²; p = 0.03). This segment also showed a trend for smaller stent areas (p = 0.05 to 0.09), and a bigger neointimal area relative to the stent area (DKC: 8.94 [5.43 to 10.5]% vs. rTAP: 4.75 [0.08 to 8.5]%; p = 0.06) in the DKC patients. The incidence of clinical events was comparably low in both groups. At 6-months, OCT showed a similar change in the SB ostial area (primary endpoint) in rTAP compared to DKC. There was also a trend for smaller luminal areas in the confluence polygon and the distal parent vessel, and a larger neointimal area relative to the stent area, in DKC, along with a tendency for more malapposed stent struts in rTAP. https://clinicaltrials.gov/ct2/show/NCT03714750, identifier: NCT03714750.