Occurrence Of Adverse Clinical Events Research Articles

Right ventricular dyssynchrony for the prediction of prognosis in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension: a study with two-dimensional speckle tracking.

Pulmonary arterial hypertension (PAH) is a common complication of systemic lupus erythematosus (SLE), and PAH can cause right ventricle (RV) remodel and dyssynchrony. The aim of this study was to explore the value of RV dyssynchrony in predicting adverse clinical events in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension (SLE-PAH) using two-dimensional speckle tracking echocardiography (2D-STE). A total of 53 patients with SLE-PAH were enrolled in this study. The dyssynchrony of the RV (RV-SD6) was evaluated by 2D-STE. The clinical data of all participants were collected, and routine cardiac function parameters were measured by two-dimensional echocardiography, and analyzed for their correlation with RV-SD6. The predictive value of RV-SD6 in clinical adverse event was evaluated. RV-SD6 was negatively correlated with RV-FLS, RV-FAC, and TAPSE (r = -0.788, r = -0.363 and r = -0.325, respectively, all P < 0.01), while the correlation with RV-FLS was the strongest. linear regression analysis showed that RV-FLS was an independent risk factor for RV-SD6 (β = -1.40, 95% CI -1.65 ~ -1.14, P < 0.001). Cox regression analysis showed that RV-SD6 was a predictor with clinical adverse events (HR = 1.03, 95% CI 1 ~ 1.06, P < 0.05). RV-SD6 was highly discriminative in predicting clinical adverse events (AUC = 0.764), at a cutoff of 51.10ms with a sensitivity of 83.3% and specificity of 68.3%. RV-FLS was negatively correlated with RV-SD6 and was an independent risk factor for it. RV-SD6 can serve as an indicator for predicting the occurrence of adverse clinical events in SLE-PAH patients, with high sensitivity and specificity.

The impact of concomitant metabolic dysfunction-associated fatty liver disease on adverse outcomes in patients with hepatitis B cirrhosis: a propensity score matching study.

In cirrhotic patients, the clinical relevance of metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. We aimed to research the relationship between MAFLD and adverse clinical outcomes in patients with hepatitis B cirrhosis. A total of 439 patients with hepatitis B cirrhosis were enrolled. Abdominal MRI and computed tomography were used to calculate liver fat content in order to evaluate steatosis. The Kaplan-Meier method was implemented to generate survival curves. The independent risk factors for prognosis were identified by multiple Cox regression. Propensity score matching (PSM) was used to reduce the influence of confounding factors. This study explored the relevance between MAFLD and mortality, first decompensation and further decompensation. In our study, most patients were decompensated cirrhosis (n = 332, 75.6%) and the ratio of decompensated cirrhosis patients in non-MAFLD to MAFLD group was 199 : 133. Compared to the non-MAFLD group, patients with MAFLD had worse liver function which mainly reflected that there were more Child-Pugh C patients and higher model for end-stage liver disease score in the MAFLD group. A total of 207 adverse clinical events occurred in the total cohort during a median follow-up of 47 months, including 45 deaths, 28 hepatocellular carcinoma, 23 first decompensation and 111 further decompensation. Cox multivariate analysis showed that MAFLD was an independent risk factor for death [hazard ratio (HR) 1.931; 95% confidence interval (CI) 1.019-3.660; P = 0.044 HR 2.645; 95% CI, 1.145-6.115; P = 0.023] and further decompensation (HR 1.859; 95% CI, 1.261-2.741; P = 0.002 HR 1.953; 95% CI, 1.195-3.192; P = 0.008) before and after PSM. In decompensated group with MAFLD, diabetes had a more significant effect on adverse prognosis than overweight or obesity and other metabolic risk factors. In patients with hepatitis B cirrhosis, concomitant MAFLD can predict a higher risk of further decompensation and death among decompensated individuals. According to patients among MAFLD, diabetes may be a major factor in the occurrence of adverse clinical events.

Predictive value of left atrial strain analysis in adverse clinical events in patients with hypertrophic cardiomyopathy: a CMR study

BackgroundA subset of patients with hypertrophic cardiomyopathy (HCM) will experience adverse clinical events such as heart failure (HF), cardiovascular death, and new-onset atrial fibrillation (AF). Current risk stratification methods are imperfect and limit the identification of patients at high risk for HCM. This study aimed to evaluate the role of cardiac magnetic resonance (CMR)-derived left atrial strain parameters in the occurrence of adverse clinical events in patients with HCM.MethodsLeft atrial (LA) structural, functional, and strain parameters were evaluated in 99 patients with HCM and compared with 89 age-, sex-, and BMI-matched control subjects. LA strain parameters were derived from CMR two- and four-chamber cine images by a semiautomatic method. LA strain parameters include global longitudinal strain (GLS) and global circumferential strain (GCS). The LA GLS includes reservoir strain (GLS reservoir), conduit strain (GLS conduit), and booster strain (GLS booster). Three LA GLS strain rate (SR) parameters were derived: SR reservoir, SR conduit, and SR booster. The primary endpoint was set as a composite of adverse clinical events, including SCD, new-onset or worsening to hospitalized HF, new-onset AF, thromboembolic events, and fatal ventricular arrhythmias.ResultsLA GLS, GLS SR and GCS were impaired in HCM patients compared to control subjects (all p < 0.001). After a mean follow-up of 37.94 ± 23.69 months, 18 HCM patients reached the primary endpoint. LA GLS, GLS SR, and GCS were significantly lower in HCM patients with adverse clinical events than in those without adverse clinical events (all p < 0.05). In stepwise multiple Cox regression analysis, LV SV, LA diameter, pre-contraction LAV (LAV pre-ac), passive LA ejection fraction (EF), and LA GLS booster were all independent determinants of adverse clinical events. LA GLS booster ≤ 8.9% was the strongest determinant (HR = 8.9 [95%CI (1.951, 40.933)], p = 0.005). Finally, LA GLS booster provided predictive adverse clinical events value (AUC = 0.86 [95%CI 0.77–0.98]) that exceeded traditional outcome predictors.ConclusionLA strain assessment, a measure of LA function, provides additional predictive information for established predictors of HCM patients. LA GLS booster was independently associated with adverse clinical events in patients with HCM.

Цитомегаловирусная инфекция как фактор риска неблагоприятных сердечно-сосудистых событий у больных с хронической сердечной недостаточностью

The purpose — to study the effect of cytomegalovirus (CMV) infection on the production of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and its relationship with functional status in patients with chronic heart failure (CHF) of ischemic genesis. Material and methods. We examined 187 patients with CHF of ischemic etiology, hospitalized in the cardiology department for decompensated heart failure (functional class (FC) CHF II-IV). Subsequently, patients were prospectively monitored for 24 months. The end point was a combined one and was defined as an increase by 1 or more in the FC of CHF (according to NYHA), hospitalization for decompensation of CHF, progressive deterioration of the structural and functional parameters of the left ventricle during the study period, the occurrence of adverse clinical events (cardiovascular death, non-fatal myocardial infarction or acute cerebrovascular accident, pulmonary embolism) during 24 months of prospective observation. After stabilization of patients upon inclusion in the study, plasma concentrations of TNF-α and IL-1β were determined by enzyme-linked immunosorbent assay. Qualitative determination of cytomegalovirus DNA in blood was carried out using the polymerase chain reaction method. Results. Based on the results of quantitative determination of CMV DNA, patients were divided into two groups: group 1 — seropositive (CMV+) (n = 128) and group 2 — seronegative (CMV-) (n = 59). In seropositive patients, functional class IV of CHF was significantly more often recorded (p &lt; 0.035), as well as higher levels of TNF-α (p &lt; 0.001) and IL-1β (p &lt; 0.001) regardless of the FC of CHF. In the group of patients with positive CMV serostatus, adverse cardiovascular events were recorded significantly more often during 24 months of observation compared to seronegative patients: there was a significantly higher number of hospitalizations due to decompensation of CHF (p = 0.023), development of acute coronary syndrome (p = 0.031) and pulmonary embolism (p = 0.042), and lethal cases (p = 0.018). Conclusion. High levels of proinflammatory cytokines in patients with CHF correlate with carriage of CMV infection. Seropositive patients have an increased risk of adverse cardiovascular events compared to seronegative patients with CHF.

Abstract 11427: Clot Strength and Platelet Reactivity for Prediction of Major Cardiovascular Events After Percutaneous Coronary Intervention

Introduction: Platelet-fibrin clot strength (PFCS) is associated with the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Hypothesis: The interaction between PFCS and platelet reactivity, and their prognostic implication remain uncertain. Methods: We enrolled CAD patients undergoing percutaneous coronary intervention (PCI) with available PFCS (measured by thromboelastography) and platelet reactivity (measured by VerifyNow). PFCS High was defined as maximal amplitude (MA)≥68, and high platelet reactivity (HPR) was categorized as P2Y12 reaction unit (PRU) &gt;208. Patients were stratified into 4 groups according to the levels of MA and PRU: (1) normal platelet reactivity (NPR)-PFCS Low (31.9%); (2) HPR-PFCS Low (28.9%); (3) NPR-PFCS High (18.1%); and (4) HPR-PFCS High (21.1%). The primary endpoint was MACE (a composite of all-cause death, myocardial infarction, or stroke) and the risk of major bleeding was also evaluated. Results: At 4-year follow-up, prognostic implication of HPR and PFCS High showed the synergistic effect, and risks of MACE were significantly different across the groups (log-rank test, P &lt; 0.001) (Figure 1). Compared with the NPR-PFCS Low group, the HPR-PFCS High group only showed a significantly higher risk of MACE (adjusted hazard ratio [HR adj ]: 1.87; 95% confidence interval [CI]: 1.22-2.87; p=0.004). In addition, the HPR-PFCS High group had a greater rate of MACE compared with the HPR-PFCS Low group (HR adj : 1.47; 95% CI: 1.04-2.09; p=0.03). Similar results were revealed in the risk of all-cause death. Compared with HPR-PFCS Low , NPR-PFCS Low was associated with a higher major bleeding rate (HR adj : 3.03; 95% CI: 1.27-7.14; p=0.01). Conclusions: In PCI-treated patients, PFCS and HPR phenotypes show important relationships in the occurrence of adverse clinical events. Therefore, a combined assessment of clot strength and platelet reactivity may enhance post-PCI risk stratification.

Use of Anticoagulant Therapy in Patients with Acute Myocardial Infarction and Atrial Fibrillation.

The incidence of atrial fibrillation (AF) in acute coronary syndrome (ACS) ranges from 2.3–23%. This difference in the incidence of AF is explained by the different ages of the patients in different studies and the different times of application of both reperfusion and drug therapies in acute myocardial infarction (AMI). About 6–8% of patients who underwent percutaneous intervention within AMI have an indication for oral anticoagulant therapy with vitamin K antagonists or new oral anticoagulants (NOAC).The use of oral anticoagulant therapy should be consistent with individual risk of bleeding as well as ischemic risk. Both HAS-BLED and CHA2DS2VASc scores are most commonly used for risk assessment. Except in patients with mechanical valves and antiphospholipid syndrome, NOACs have an advantage over vitamin K antagonists (VKAs). One of the advantages of NOACs is the use of fixed doses, where there is no need for successive INR controls, which increases the patient’s compliance in taking these drugs. The use of triple therapy in ACS is indicated in the case of patients with AF, mechanical valves as well as venous thromboembolism. The results of the studies showed that when choosing a P2Y12 receptor blocker, less potent P2Y12 blockers such as Clopidogrel should be chosen, due to the lower risk of bleeding. It has been proven that the presence of AF within AMI is associated with a higher degree of reinfarction, more frequent stroke, high incidence of heart failure, and there is a correlation with an increased risk of sudden cardiac death. With the appearance of AF in ACS, its rapid conversion into sinus rhythm is necessary, and in the last resort, good control of heart rate in order to avoid the occurrence of adverse clinical events.

Impact of the initial decline in estimated glomerular filtration rate on the risk of new-onset atrial fibrillation and adverse cardiovascular and renal events in patients with type 2 diabetes treated with sodium-glucose co-transporter-2 inhibitors.

To investigate the impact of initial decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes (T2D) following sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment. We used medical data from a multicentre healthcare provider in Taiwan and recruited 11 769 patients with T2D with baseline/follow-up eGFR data available after 1 to 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2018. Patients were followed up from the drug index date until the occurrence of adverse clinical events, SGLT2i discontinuation or the end of the study period, whichever took place first. Overall, SGLT2i treatment was associated with an initial eGFR decline of 3.5% ± 14.0% after a median treatment period of 10 weeks. A total of 37.1% (n=4371) of patients experienced no eGFR decline, and 30.5% (n=3593), 20.2% (n=2376), 8.5% (n=999) and 3.7% (n=430) of patients experienced an eGFR decline of 0%-10%, 10%-20%, 20%-30% and more than 30%, respectively. The mean eGFR over time became stable after 6 months in all eGFR decline categories, even in the group with a pronounced eGFR decline of more than 30%. Compared with no eGFR decline, an initial eGFR decline of 0%-10%, 10%-20% or 20%-30% was not associated with a higher risk of atrial fibrillation (AF), major adverse cardiovascular events (MACE, including ischaemic stroke, systemic embolism and acute myocardial infarction)/heart failure (HF) and composite renal outcome (doubling of the serum creatinine level/end-stage kidney disease), whereas an eGFR decline of more than 30% was associated with a higher risk of new-onset AF (adjusted hazard ratio [aHR]=2.20, 95% confidence interval [CI]=1.40-3.47), MACE/HF (aHR=2.09, 95% CI=1.04-4.17) and composite renal outcome (aHR=1.82, 95% CI= 1.18-2.83). The multivariate analysis indicated that the use of a diuretic or insulin, presence of stroke, older age, female sex, a higher HbA1c level, and a lower body mass index of less than 25 kg/m2 were independent factors associated with an eGFR decline of more than 30% following SGLT2i initiation. A pronounced eGFR decline of more than 30% following SGLT2i treatment was associated with adverse cardiovascular or renal events among patients with T2D.

OP340 Adverse Clinical Events And Associated Risk Factors In Patients With Very-High-Risk Atherosclerotic Cardiovascular Disease

IntroductionClinical atherosclerotic cardiovascular disease (ASCVD) patients are judged to be very-high-risk if they had a history of multiple major ASCVD events, or one major ASCVD event with multiple high-risk conditions. Very-high-risk ASCVD patients are under high risk of adverse clinical events and need more attention in the management of secondary prevention. This real-world study aimed at estimating the prevalence of very-high-risk ASCVD and investigating the occurrence of adverse clinical events and associated risk factors among patients with very-high-risk ASCVD in China.MethodsData were obtained from the Urban Employee Basic Medical Insurance database in Tianjin, China. Very-high-risk ASCVD patients were identified from 2014 to 2015 through the history of ASCVD events and evidence of high-risk conditions, and followed for 24 months. Adverse clinical events were measured by major adverse cardiovascular events (MACE), a composite endpoint of stroke, myocardial infarction (MI) and death. A Cox regression model was used to identify risk factors of MACE, adjusting for potential confounders.ResultsThe percentage of clinical ASCVD patients identified as very-high-risk was 35.2 (N = 41,181), while 34,740 patients with continuous enrollment were included (mean age: 67.1 years; 42.5% female). The percentage of patients who had MACE in the 24-month follow-up period was 27.7, with stroke (22.3%) as the most prevalent event followed by death (6.9%) and MI (1.3%). Male gender, older age, and having MI or ischemic stroke (versus unstable angina) as the index major ASCVD event were risk predictors of MACE.ConclusionsMore than one-third of patients with clinical ASCVD are under very-high-risk in China, and among them 27.7 percent experience MACE during a 24-month follow-up period. Male patients, older patients, and patients who had MI or ischemic stroke are under higher risk of experiencing MACE. Future studies are warranted for comparing the differences in characteristics, pattern of drug use, occurrence of adverse clinical events and medical burden between very-high-risk ASCVD patients and ASCVD patients not at very-high-risk.

A Prospective Randomized Investigation Comparing Functional Outcomes of Syndesmotic Suture-Button Fixation to Screws

AIM : To compare functional outcomes and adverse events of surgically treated syndesmotic injuries with either screws(s) or a suture-button device(s). It was hypothesized that suture-button fixation would provide equal clinical results with fewer adverse events. MATERIALS AND METHODS : Multi-center, randomized clinical study. Sixty-five subjects with confirmed acute syndesmotic injury requiring surgical intervention were enrolled. Subjects were randomized and treated with either suture-button or screw fixation. Foot and Function Index pain, disability, and activity scores, American Orthopaedic Foot and Ankle Society, and the Visual Analogue Scale for pain were reported up until 12-months. The adverse events were also collected. The forty subjects with complete data up to one year (n=40; suture-button =18 and screw=22) were included in analysis. Single or multiple screws or suture-button implants were based on surgeon preference and patients’ characteristics. RESULTS : There was statistically significant improvement in Foot and Function Index and American Orthopaedic Foot and Ankle Society scores with both techniques (p 0.05). Syndesmotic screws had higher adverse events compared to suture-button (32 % versus 6%), which approached statistical significance (p = 0.054). CONCLUSION : One-year clinical data suggests that acute syndesmotic injuries can be effectively treated with either technique. An important benefit of suture-button fixation is a lower occurrence of adverse clinical events.

A cross-sectional multisite exploration of Italian paediatric nurses' reported burnout and its relationship to perceptions of clinical safety and adverse events using the RN4CAST@IT-Ped.

To explore Italian paediatric nurses' reported burnout and its relationship to their perceptions of safety and adverse events. A cross-sectional study using the RN4CAST@IT-Ped database with a web-based survey design. The RN4CAST@IT-Ped questionnaire was used to collect data in 2017. This comprised three main components: three dimensions (22 items) of the Maslach Burnout Inventory including emotional exhaustion, depersonalization and personal accomplishment. Participants also scored an overall grade of patient safety and estimated the occurrence of adverse clinical events. Nurses (N=2,243) reported high levels of burnout. Most rated clinical safety as high. The risk of adverse events ranged from 1.3-12.4%. The degree of burnout appeared to influence the perception of safety and adverse events. The association between nurses' burnout and perceptions of higher rates of adverse events and reduced safety in clinical practice is an important finding. However, it is unclear whether this was influenced by a negative state of mind, and whether reduced safety and increased adverse events negatively influenced nurses' well-being, thus leading to burnout. Regardless, the association between nurses' burnout and these quality concepts needs further exploration to examine the effect, if any, on burnout and safety, and identify supportive mechanisms for nurses. The association between reported burnout and perception of safety and risk of adverse events in Italian paediatric nurses has been reported for the first time. Nurses reporting burnout are at greater risk of intensely negative perceptions of clinical safety and adverse events. This is an important finding as perceptions can influence practice and behaviours. Quality measures in children's clinical environments need to go beyond obvious indicators to examine nurses' well-being as this also influences quality and safety.

Ventricular arrhythmias in patients with biventricular assist devices.

Ventricular arrhythmias (VAs) are common in patients after left ventricular assist device (LVAD) implant and are associated with worse outcomes. However, the prevalence and impact of VA in patients with durable biventricular assist device (BIVAD) is unknown. We performed a retrospective cohort study of patients with BIVADs to evaluate the prevalence of VA and their clinical outcomes. Consecutive patients who received a BIVAD between June 2014 and July 2017 at our medical center were included. The prevalence of VA, defined as sustained ventricular tachycardia or fibrillation requiring defibrillation or ICD therapy, was compared between BIVAD patients and a propensity-matched population of patients with LVAD from our center. The occurrence of adverse clinical events was compared between BIVAD patients with and without VA. Of the 13 patients with BIVADs, 6 patients (46%) experienced clinically significant VA, similar to a propensity-matched LVAD population (38%, p = 1.00). There were no differences in baseline characteristics between the two cohorts, except patients in the non-VA group who had worse hemodynamics (mitral regurgitation and right-sided indices), had less history of VA, and were younger. BIVAD patients with VA had a higher incidence of major bleeding (MR 3.05 (1.07-8.66), p = 0.036) and worse composite outcomes (log-rank test, p = 0.046). The presence of VA was associated with worse outcomes in both LVAD and BIVAD groups. Ventricular arrhythmias are common in patients with BIVADs and are associated with worse outcomes. Future work should assess whether therapies such as ablation improve the outcome of BIVAD patients with VA.

Postoperative adverse events in patients with diabetes undergoing orthopedic and general surgery.

Factors that may result in the occurrence of adverse clinical events in diabetic patients during the postoperative period are not entirely clear. This study evaluated factors that may cause adverse events following elective orthopedic or general surgery.Patients with diabetes who underwent orthopedic or general surgery between January 2010 and October 2015 were retrospectively selected from the General Hospital of People's Liberation Army database. Factors associated with postoperative adverse events were analyzed using multivariable logistic regression.Among 1525 patients included, mean age was 63.5 ± 10.8 years and mean duration of diabetes was 8.8 ± 6.6 years. Among them, 49.9% underwent orthopedic surgery and 50.1% underwent general surgery. Postoperatively, 118 (7.7%) patients had adverse events, including delayed extubation (n = 43, 36.4%), circulatory disorder (n = 15, 12.7%), respiratory and circulatory abnormalities (n = 23, 19.5%), nonhealing of the incision (n = 11, 9.3%), infections at other sites (n = 15, 12.7%), other complications (n = 8, 6.8%), and death (n = 3, 2.5%). Multivariable regression analysis showed that age >65 years old [odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.25–3.98], male sex (OR = 2.14, 95% CI: 1.24–3.38), postoperative peripheral blood glucose (OR = 1.13, 95% CI: 1.13–1.82), diabetic complications (OR = 2.41, 95% CI: 1.36–4.28), abnormal kidney function (OR = 2.73, 95% CI: 1.13–6.58) and general surgery (OR = 1.48, 95% CI: 1.11–5.26) were associated with the occurrence of postoperative adverse events.In patients with diabetes undergoing intermediate or major elective surgery, older age, male sex, high postoperative peripheral blood glucose, diabetic complications, abnormal kidney function, and general surgery type were associated with the occurrence of postoperative adverse events.

Association between CYP2C19*2/*3 Polymorphisms and Coronary Heart Disease.

This study sought to explore the relationship between cytochrome P450 2C19 (CYP2C19) *2/*3 polymorphisms and the development of coronary heart disease (CHD), and to evaluate the influence of the single nucleotide polymorphisms (SNPs) on the occurrence of adverse clinical events in CHD patients. A total of 231 consecutive patients candidate for percutaneous coronary intervention genotyped for CYP2C19*2 (681G>A) and *3 (636G>A) polymorphisms were enrolled. The adverse clinical events were recorded during a follow-up period of 14 months. The incidence of CHD, according to coronary angiography, was significantly higher (P=0.025) in CYP2C19*2 carriers group. Stepwise binary logistic regression analysis revealed that among factors that potentially influenced the presence of CHD (age>60 years, gender, BMI, etc.), CYP2C19*2 carriers (OR 1.94, 95% CI: 1.08-3.50, P=0.028) and male gender (OR 2.74, 95% CI: 1.58-4.76, P=0.001) were independent predictors, which were associated with the presence of CHD. The follow-up results showed that the incidence of adverse cardiovascular events within 14 months of discharge was significantly higher in the CYP2C19*2 carriers than in the non-carriers (21.6% vs. 6.3%, P=0.019). The results of the multivariate Cox proportional hazards model showed that CYP2C19*2 loss-of-function was the only independent factor which predicted the coronary events during the follow-up period of 14 months (OR=3.65, 95% CI 1.09-12.25, P=0.036). The adverse impact of CYP2C19*2 polymorphisms was found not only in the risk of the presence of CHD, but also in the adverse cardiovascular events in CHD patients during the follow-up period of 14 months. However the same influence was not found in CYP2C19*3 mutation in Chinese Han population.

Clinical adverse events in prehospital patients with ST-elevation myocardial infarction transported to a percutaneous coronary intervention centre by basic life support paramedics in a rural region.

It remains unclear whether ST-elevation myocardial infarction (STEMI) patients transported by ambulance over long distances are at risk for clinical adverse events. We sought to determine the frequency of clinical adverse events in a rural population of STEMI patients and to evaluate the impact of transport time on the occurrence of these events in the presence of basic life support paramedics. We performed a health records review of 880 consecutive STEMI patients transported to a percutaneous coronary intervention centre. Patients had continuous electrocardiogram and vital sign monitoring during transport. A classification of clinically important and minor adverse events was established based on a literature search and expert consensus. A multivariate ordinal logistic regression model was used to study the association between transport time (0-14, 15-29, ≥30 minutes) and the occurrence of overall clinical adverse events. Clinically important and minor events were experienced by 18.5% and 12.2% of STEMI patients, respectively. The most frequent clinically important events observed were severe hypotension (6.1%) and ventricular tachycardia/ventricular fibrillation (5.1%). Transport time was not associated with a higher risk of experiencing clinical adverse events (p=0.19), but advanced age was associated with adverse events (p=0.03). No deaths were recorded during prehospital transport. In our study of rural STEMI patients, clinical adverse events were common (30.7%). However, transport time was not associated with the occurrence of adverse clinical events in these patients.

Identification & Characterization of Novel Hemostatic Biomarkers of Adverse Clinical Events in Patients with Continuous Flow Left Ventricular Assist Device Implants

Introduction: Heart failure affects over 5 million people in the US. Its rising prevalence coupled with a lack of donor hearts has led to an increase in the use of continuous flow left ventricular assist devices (CF-VAD). However, patients with CF-VAD implants are at risk for complications such as non-surgical bleeding and thrombosis, which significantly increase the risk of patient morbidity and mortality. Identification of novel biomarkers for these events could improve current risk assessment models, treatment, and thus, quality of life for VAD implanted patients.Materials and Methods: 71 blood samples were collected peri-operatively and at varying time points post-operatively from 16 patients implanted with a Thoratec HeartMate II CF-VAD. Plasma was prepared and stored at -70°C until analysis. Plasma samples collected from normal individuals were used as controls. Samples were analyzed for annexin V-positive microparticles and microparticles exposing tissue factor, as well as plasma levels of annexin V and C-reactive protein (CRP) by ELISA. Additionally, surface-enhanced laser desorption ionization - mass spectrometry (SELDI-MS) analysis was used to identify changes in biomarker expression. The occurrence of adverse clinical events was determined using an internal RedCap database. CF-VAD thrombosis was characterized as: cerebrovascular accident/transient ischemic attack diagnosed by a neurologist, rise in LDH or plasma free hemoglobin, hemolysis, evidence of pump dysfunction consistent with thrombus identified by pump parameters, echocardiographic or computed tomographic evidence of clot, or surgical pump exchange for thrombus. CF-VAD bleeding events were characterized as: anemia and bleeding determined by a cardiologist.Results: Annexin V plasma levels were increased approximately 3-fold compared to normal plasma (9.23 ±0.85 vs. 2.76 ±0.2 nM). CRP plasma levels were significantly elevated in CF-VAD patients compared to normals (14.5 ±2.7 vs. 2.2 ± 0.6 µg/ml; p=0.034). Although the level of annexin V-positive microparticles were the same in CF-VAD patients and normals, the amount of microparticles exposing tissue factor was significantly higher in CF-VAD patients (3.7 ± 1.1 vs. 0.5 ± 0.1 pg/ml; p=0.038). SELDI-MS analysis indicated three distinct peaks that were present in CF-VAD patients, but absent from normals (8.1, 11.7 and 15.2/16.2 kDa). During the follow-up period, patients experienced 12 CF-VAD-related thrombotic events, 8 hemorrhagic events and 2 septic events. The 8.1 kDa biomarker was present in 10/12 patients with a thrombotic event, 2/6 patients with a hemorrhagic event, 0/2 patients experiencing sepsis and 0/2 patients without an adverse event. Positive correlations with the SELDI-MS peaks and measured parameters were identified: the 8.1 kDa peak was associated with elevated plasma levels of annexin V (p=0.01) and the presence of annexin V-positive microparticles (p=0.005); the 11.7 kDa peak was associated with elevated plasma levels of CRP (p=0.01); the 15.2/16.2 kDa peaks were associated with the presence of microparticle exposing tissue factor (p=0.002), annexin V-positive microparticles (p<0.001) and elevated plasma levels of annexin V (p=0.03).Conclusions: Despite treatment with low-dose aspirin and warfarin, CF-VAD patients exhibit signs of hemostatic activation. SELDI-MS may be useful in the identification of novel biomarkers of CF-VAD-associated adverse events. This data justifies further evaluation of the utility of the SELDI-MS to readily identify biomarkers related to adverse clinical events in a larger CF-VAD population. DisclosuresNo relevant conflicts of interest to declare.

Down-Regulation of Protein C Pathway Associated with Increased Inflammation in Patients with Implanted Ventricular Assist Devices As a Potential Cause of Pump Thrombosis

Introduction: The use of left ventricular assist devices (LVADs) is increasingly common in patients suffering from heart failure. However, the placement of an LVAD comes with risks, including pump thrombosis that occurs in up to 20% of patients. Pump thrombosis constitutes a major cause of death in this patient population, and understanding the mechanism behind this complication will allow its prevention. The protein C pathway is critical in the maintenance of blood hemostasis, aiding in the prevention of hypercoagulability. It is hypothesized that the state of inflammation in LVAD patients dysregulates the protein C pathway, creating a hypercoagulable state with resultant thrombosis. The objective of this project was to characterize changes in the protein C pathway in patients supported by an LVAD who experienced a thrombotic event.Materials and Methods: Citrated plasma sampleswere collected peri-operatively and at varying times post-operatively from 22 patients implanted with a Thoratec HeartMate II LVAD. Plasma samples were stored frozen (-80°C) and batch analyzed for levels of total protein S, free protein S, protein C, C-reactive protein (CRP), soluble endothelial cell protein C receptor (EPCR) and soluble thrombomodulin (TM) by ELISA. Samples near the time of an event and 1-3 months earlier were analyzed. The occurrence of adverse clinical events was determined retrospectively using an internal RedCap database. LVAD-associated thrombosis was characterized as: cerebrovascular accident/transient ischemic attack diagnosed by a neurologist, rise in LDH or plasma free hemoglobin, hemolysis, evidence of pump dysfunction consistent with thrombus identified by pump parameters, echocardiographic or computed tomographic evidence of clot, or surgical pump exchange for thrombus. A comparative group was composed of patients with LVAD-associated bleeding (the other frequent complication in this population) events characterized as: anemia and bleeding determined by a cardiologist.Results: The median level of CRP was higher and levels of total and free protein S were lower in patients with thrombotic events compared to those with bleeding events. Median levels of protein C and TM were comparable in patients with thrombotic or bleeding events. Secondly, for patients with a thrombotic event, levels of total protein S, free protein S, and protein C (but not TM or CRP) were further decreased at time near the event. No changes were observed in any of these parameters preceding or at the time of a bleeding complication. Compared to normal ranges, levels of proteins C and S were consistent with low-dose warfarin therapy (INR 1.5-2.0) given to all LVAD patients; TM levels were similar to normal (2.8 ng/ml). EPCR levels were lower than normal (828 ng/ml) in all groups with no apparent change at time of event. Compared to normal (0.8 µg/ml) CRP levels were very elevated in the thrombosis patients and slightly elevated in the bleeding patients.Conclusions: This data demonstrates excessively high CRP levels in patients who experienced LVAD-associated thrombosis. These patients also had lower total protein S and free protein S levels which decreased further at time of the thrombotic event. In the immunoassays used in this study no difference was observed between the levels of total and free protein S. Whether the up-regulated inflammatory state increases levels of the protein S linked C4b binding protein and whether the function of protein S is inhibited could not be proven here. This study suggests that protein S is a gatekeeper for the function of the protein C pathway. Clinically, in addition to measuring protein S levels and/or function, the degree of the inflammatory state should be considered as the level of C4b binding protein would be altered affecting the functionality of protein S. Our study has shown that abnormal levels of protein S and CRP are components that establish a hypercoagulable environment in LVAD implanted patients where pump thrombus develops weeks later. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Novel biomarkers predicting cardiac function after acute myocardial infarction.

Measurement of biomarkers provides a cost-effective and widely available method to estimate cardiac dysfunction and clinical outcome of patients with acute myocardial infarction (AMI). PubMed entries with terms 'myocardial infarction' and the respective biomarker. Cardiac troponins and natriuretic peptides are closely related to left ventricular dysfunction and the occurrence of adverse clinical events following AMI. The incremental value of novel biomarkers is controversial. The combination of traditional and novel biomarkers might further improve risk stratification of patients with AMI. We searched all entries on the PubMed database with the MeSH terms 'myocardial infarction' and 'cardiac troponins', 'natriuretic peptides', 'copeptin', galectin-3', 'corin', 'fetuin-A', 'adiponectin' and 'microRNA'.

OC-039 Improving the Quality of Care and Reducing Costs of IBD Patients on Biologic Therapy Through a Multi-Disciplinary Biologics Clinic

Introduction NICE IBD quality standard (QS81) and the IBD Standards aim to deliver high quality and safe clinical care to IBD patients throughout the UK that is patient-centred and evidence based. These aims are supported by the national biologic therapy audit. To improve and standardise the care of our IBD patients on biologic therapy we began a weekly multi-disciplinary (physicians, IBD nurses, and pharmacist) virtual biologics clinic (VBC). Here, the response to therapy is monitored (clinical scoring, well-being, laboratory results), the scheduling of investigations are coordinated, and the review and writing of prescriptions undertaken. Methods We prospectively collected data from our VBC for 8 consecutive weeks. Changes to therapy on clinical grounds were noted, and the financial implications of these changes calculated. Calculations for IFX savings were based on an average dose of 300 mg per patient plus infusion costs. The ordering of required investigations and the occurrence of adverse clinical events were recorded. Results In 8 weeks, 360 patient reviews were performed relating to 327 patients (IFX = 207, ADA = 79, VEDO = 41). Therapy was adjusted in 41/327 patients (12.5%). 5 stopped biologic therapy, 19 switched drug, 10 reduced and 7 increased therapy frequency. Net saving in prescribing was £10,928 at 8 weeks (>£65 K/annum). The coordinated prescribing of medication and pharmacy sign off improved the delivery of therapy and patient satisfaction. 23 colonoscopies, 9 MR scans, and 45 outpatient appointments to assess response to therapy at 3 or 12 months, were scheduled from the VBC. 5 complications were highlighted (recurrent infection; 2 required surgery; cancer; severe IBD flare requiring hospitalisation). In total 118/357 (36%) patients had their care altered by VBC intervention (41 adjusted therapies, 77 scheduled monitoring and further clinical input. Conclusion The VBC provides a safe platform to initiate and monitor biologic therapies and to audit practices. The introduction of a multi-disciplinary VBC has altered the management of 118/327 patients (36%) based on clinical findings, results, and NICE guidance. Significant financial savings (£65 K per annum), the streamlining of prescribing, and superior patient monitoring have helped to improve the quality and safety of care provided. The transition to biosimilar anti-TNF therapies can also be facilitated using a VBC forum. Disclosure of Interest None Declared

PTH-060 Better Care for IBD Biologic Patients: The Impact of A Multi-Disciplinary Virtual Clinic

Introduction The IBD Standards, the Royal College of Physicians national biologic audit, and the NICE IBD quality standard (QS81) all aim to help deliver high quality, safe and appropriate clinical care to IBD patients throughout the UK. In line with these recommendations, and to improve and standardise the care of our IBD patients on biologic therapies we began a weekly multi-disciplinary (physicians, IBD nurses, and pharmacist) virtual biologics clinic (VBC). Here, the response to therapy is monitored (clinical scoring, well-being, laboratory results), the scheduling of investigations are coordinated, and the review and writing of prescriptions undertaken. Methods We prospectively collected data from our VBC for 8 consecutive weeks. Changes to therapy on clinical grounds were noted, and the financial implications of these changes calculated. Calculations for IFX savings were based on an average dose of 300 mg per patient, plus infusion costs. The ordering of required investigations and the occurrence of adverse clinical events were recorded Results In 8 weeks, 360 patient reviews were performed relating to 327 patients (IFX = 207, ADA = 79, VEDO = 41). Therapy was adjusted in 41/327 patients (12.5%). 5 stopped biologic therapy, 19 switched drug, 10 reduced and 7 increased the frequency of therapy. Net saving was £10,928 at week 8 (>£65 K/annum). The coordinated prescribing of medication and pharmacy sign off improved the delivery of therapy and patient satisfaction. 23 colonoscopies, 9 MR scans, and 45 outpatient appointments to assess response to therapy at 3 or 12 months and clinical input were scheduled from the VBC. The ordering of anti-TNF drug and antibody levels solely through the VBC reduced any duplication of requests and ensured the review and actioning of results. 5 complications were highlighted (recurrent infections; 2 requiring surgery; cancer; severe IBD flare requiring hospitalisation). Conclusion The introduction of a multi-disciplinary VBC has altered the management of 41/327 patients (12.5%) based on clinical findings and the results of investigations. Significant financial savings (£65 K per annum), the streamlining of prescribing, and superior patient monitoring have helped to improve the quality and safety of care provided. With better monitoring, care, NICE compliance, and financial prudence, this will help to sustain or service and practices. Disclosure of Interest None Declared

Physical Activity as Healthy Intervention Against Severe Oxidative Stress in Elderly Population.

Severe oxidative stress is a relevant risk factor for major deleterious health-related events in older people and is thought to be an important contributor to age-related disease. Literature has suggested oxidative stress as a therapeutic target for mitigating the biological decline and attenuating the occurrence of adverse clinical events in aged individuals. However, definitive treatments are not known. Regular and moderate physical activity has been proposed as possible intervention for slowing age-related decline. This healthy strategy presents a wide range of beneficial aspects for elderly, from the reduction of morbidity, disability, frailty and mortality rates to treatment of many age-related disorders. Importantly, the global benefits on health are not shared by any other strategies. Nevertheless, the physiological basis by which exercise produces its benefits to the organism is not fully understood. This review summarizes the evidence for the role of physical activity as potential healthy intervention for mitigating the negative aspects of aging through the modulation of the oxidative mechanisms.