Preprocedural Levels Research Articles

Abstract 13470: Circulating microRNA-122-5p is Associated With a Lack of Improvement in Left-Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes via Extracellular Vesicles

Transcatheter aortic valve replacement is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic AVS. However, a specific role for circulating microRNAs in the improvement of cardiac function for patients after TAVR has not yet been investigated. Methods: Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs were significantly deregulated in AVS patients on day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day seven (r=-0.264 and p=0.015) and at six months (r=-0.328 and p=0.0018). Results: By utilization of patient-derived samples and a murine AVS model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced AVS mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in ECs in comparison to cardiomyocytes. Co-culture, copy-number analysis, and immunofluorescence demonstrated that miR-122-5p can be shuttled via large EVs from ECs into cardiomyocytes. Gain- and loss-of-function suggested that EV-shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes. Mechanistically, mass spectrometry, miR-pull down, EMSA, and RNA-IP experiments confirmed that miR-122-5p interacts with the RBP, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling, miR-122-5p reduces the expression of the anti-apoptotic gene BCL2 , by binding to its 3' untranslated region to inhibit its translation. Conclusion: Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR.

Relationship Between Preprocedural Lipid Levels and Periprocedural Myocardial Injury in Patients Undergoing Elective Percutaneous Coronary Intervention

Periprocedural myocardial injury is a predictor of cardiovascular morbidity and mortality after percutaneous coronary intervention. The authors examined the effects of preprocedural lipid levels (low-density lipoprotein, high-density lipoprotein, and triglycerides) in 977 patients with coronary artery disease who underwent elective percutaneous coronary intervention. Elevated cardiac troponin I level (≥5× the upper limit of normal) was used to indicate periprocedural myocardial injury. Serum lipid samples were collected 12 hours preprocedurally. Cardiac troponin I was collected 1, 6, and 12 hours postprocedurally. Correlations between preprocedural lipid levels and postprocedural cardiac troponin I were studied. Low-density lipoprotein levels were less than 70 mg/dL in 70% of patients and greater than 100 mg/dL in only 7.4% of patients; 13% had triglyceride levels greater than or equal to 150 mg/dL, and 96% had high-density lipoprotein levels less than 40 mg/dL. Patients with elevated cardiac troponin I had significantly lower left ventricular ejection fraction than did those with cardiac troponin I levels less than 5× the upper limit of normal (P = .01). Double-and triple-vessel disease were more common in patients with elevated cardiac troponin I (P < .002). Multivariable logistic and linear regression analyses revealed no statistically significant associations between lipid levels and postprocedural cardiac troponin I elevation, possibly because such large proportions of included patients had low levels of low-density lipoprotein (70%) and a history of statin intake (86%). The authors found no association between lipid profile and periprocedural myocardial injury.

Circulating microRNA-122-5p is associated with a lack of improvement in left-ventricular function after TAVR and regulates viability of cardiomyocytes via extracellular vesicles

Abstract Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis (AVS). However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Herein, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EV-miRNAs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes. Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in aortic stenosis patients at day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day seven (r=−0.264 and p=0.015) and at six months (r=−0.328 and p=0.0018) after TAVR. At the three-year follow-up, patients with a higher level of miR-122-5p displayed significantly increased cardiovascular mortality (p=0.03). By utilization of patient-derived samples and a murine aortic-stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced aortic-valve-stenotic mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocytes dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells in comparison to cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes and regulates the viability of cardiomyocytes. Mechanistically, miR pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation confirmed that miR-122-5p interacts with the RNA-binding protein, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling into recipient cells, miR-122-5p reduces the expression of the anti-apoptotic gene BCL2, by binding to its 3' untranslated region to inhibit its translation, and thereby decreasing the viability of target cardiomyocytes. Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. Extracellular vesicular shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): German Research Foundation (DFG)German Society of Cardiology (DGK)

Prognostic Nutritional Index Predicts Contrast-Induced Nephropathy in Patients with Acute Coronary Syndrome.

This study evaluated the effectiveness of prognostic nutritional index (PNI) in predicting contrast induced nephropathy (CIN) in patients with acute coronary syndrome (ACS). This study included 925 ACS patients (mean age 62.5 ± 12.4years, 73.5% male); 604 were diagnosed as unstable angina pectoris/non-ST-elevation myocardial infarction (USAP/NSTEMI) and 321 as ST-elevation myocardial infarction (STEMI). The PNI formula was: 10 × serum albumin (g/dL) + .005 × total lymphocyte count (/mm3). The patients were divided into two groups: CIN (n = 232) and non-CIN (n = 693). Patients without CIN had a significantly lower PNI than patients with CIN (44.3 ± 6.9 vs 54.7 ± 7.4; P < .001). In the receiver operating characteristic (ROC) curve analysis, the cut-off value for PNI of 48.6 has 80% specificity and 81% sensitivity in predicting CIN (area under the ROC curve (AUC): .87, 95% CI [.84-.89]). PNI <48.6 (odds ratio (OR): 6.765, P < .001), pre-procedural creatinine levels (OR: 6.223, P < .001), left ventricular ejection fraction (LVEF) (OR: .960, P < .001), age (OR: 1.025, P = .005), diabetes mellitus (DM) (0R: 1.768, P = .006), contrast amount (OR: 1.003, P = .038), and having STEMI (OR: .594, P = .029) were found independently associated with CIN. PNI is a strong independent predictor of CIN in ACS patients.

Low apolipoprotein A1 was associated with increased risk of cancer mortality in patients following percutaneous coronary intervention: A 10-year follow-up study.

Previous studies showed that elevated apolipoprotein A1 (ApoA1) and high‐density lipoprotein cholesterol (HDL‐C) predicted reduced risk of cardiovascular‐related (CV) mortality in patients following percutaneous coronary intervention (PCI). Nevertheless, as the association between ApoA1 and cancer mortality in this population has been rarely addressed, our study aimed to evaluate prognostic impact of ApoA1 on multiple types of cancer mortality after PCI. This is a retrospective analysis of a single‐center prospective registry database of patients who underwent PCI between 2000 and 2018. The present study enrolled 3835 patients whose data of serum ApoA1 were available and they were divided into three groups according to the tertiles of the preprocedural level of ApoA1. The outcome measures were total, gastrointestinal, and lung cancer mortalities. The median and range of the follow‐up period between the index PCI and latest follow‐up were 5.9 and 0‐17.8 years, respectively. Consequently, Kaplan‐Meier analyses showed significantly higher rates of the cumulative incidences of total, gastrointestinal, and lung cancer mortality in the lowest ApoA1 tertile group compared to those in the highest. In contrast, there were no significant differences in all types of cancer mortality rates in the groups divided by the tertiles of HDL‐C. Multivariable Cox proportional hazard regression analysis adjusted by cancer‐related prognostic factors, such as smoking status, identified the elevated ApoA1 as an independent predictor of decreased risk of total and gastrointestinal cancer mortalities. Our study demonstrates the prognostic implication of preprocedural ApoA1 for predicting future risk of cancer mortality in patients undergoing PCI.

Impact of Periprocedural Myocardial Infarction on 10-Year Mortality After Coronary Stent Implantation in Patients With Diabetes Mellitus

The long-term prognostic implication of periprocedural myocardial infarction (PMI) after coronary stent implantation in patients with diabetes mellitus (DM) remains unclear. We assessed the incidence and size of PMI and the impact of PMI on 10-year all-cause and cardiac deaths using competing risk analysis in 1,095 patients, including 453 patients with DM. All patients had normal preprocedural creatinine kinase-myocardial band levels and underwent their first elective sirolimus-eluting stent implantation for stable angina pectoris. Comparing patients with and without DM, the incidence of PMI was 4.4% versus 5.9% (p=0.34) and the size of PMI (median of postprocedural peak creatinine kinase-myocardial band) was 34.6 versus 31.6IU/L (p=0.58). The cumulative incidence of 10-year all-cause and cardiac deaths significantly differed between patients with and without PMI only in patients with DM (log-rank p=0.03 and Gray's test p=0.014, respectively). In the multivariable analysis using the Fine-Gray model, PMI was a significant prognostic factor for cardiac death only in patients with DM (hazard ratio 3.82, 95% confidence interval 1.57 to 9.30, p=0.003). In conclusion, the incidence and size of PMI did not significantly differ between patients with and without DM. However, PMI was a significant prognostic factor for 10-year all-cause and cardiac deaths only in patients with DM who underwent elective sirolimus-eluting stent implantation.

The mitral inflow E/A ratio before the procedure may predict late recurrence after pulmonary vein isolation using second-generation cryoballoon

Abstract Funding Acknowledgements Type of funding sources: None. Background The left ventricular (LV) diastolic dysfunction (DD) increases the risk of atrial fibrillation (AF) development. Some studies investigated whether a relationship between DD and late recurrence after catheter ablation for AF, but they found conflictory results. Such studies had relatively short follow-up duration and they did not have a standard ablation protocol. Some patients were taken to PVI only, while additional linear lesions in localizations such as the left atrial (LA) roof, LA isthmus, and cavotricuspid isthmus were added in others. Purpose The mitral inflow E/A ratio is a simple and practical method commonly used to evaluate LV DD. We aimed to investigate whether the E/A ratio before the procedure was predictive for late recurrence in patients with AF undergoing pulmonary vein isolation (PVI) with cryoballoon (CB). Methods A total of 100 patients undergoing AF ablation for the first time using second-generation CB were included. Only patients with paroxysmal AF and sinus rhythm the day before the procedure, and with pre-procedural pro-B natriuretic peptide levels within normal limits were included. The patients with and without late recurrence were compared in terms of basal characteristics and procedural features. Any atrial tachyarrhythmia episode longer than 30 s after the blanking period was defined as late recurrence. Results The patients [age: 58.0 (50.2-62.0) years, 53 female] were followed up for a median of 44.5 (14.2-62.7) months and late recurrence developed in 25 patients. Female gender (72.0% vs 46.7%), hypertension (72.0% vs 48.0%), and the frequency of early recurrence (20.0% vs 4.0%) were found to be higher in patients with late recurrence than in those without it (p =0.028, 0.037 and 0.022, respectively). The CHA2DS2-Vasc score was higher [2.0 (1.0-3.0) vs 1.0 (0-2.0)], AF duration was longer (27.8 ± 9.4 vs 22.0 ± 8.4 months) and the E/A ratio was lower [0.5 (0.4-1.2) vs 1.4 (0.6-1.7)] in patients with late recurrence than in those without it (p=0.014, 0.006 and 0.001, respectively) (Figure 1). The groups were similar in terms of precedural features. A multivariate analysis showed that female gender (HR: 4.46, 95%CI: 1.24-15.97, p=0.021), early recurrence (HR: 10.22, 95% CI: 2.49-41.99, p=0.001), and E/A ratio (HR: 0.25, 95%CI: 0.11-0.57, p=0.001) were independent predictors for late recurrence (Figure 2). Receiver operating characteristic analysis showed that the optimal cut-off level of the E/A ratio was 0.84. Any ATa free survival rate was significantly lower in patients with E/A ratio &amp;lt;0.84 than in those with ≥0.84 (56.1% vs 88.1%, log-rank p&amp;lt;0.001). Conclusions Female gender, early recurrence, and E/A ratio are independent predictors of late recurrence in patients with AF undergoing PVI using second-generation CB. Measuring the E/A ratio in patients with sinus rhythm before AF ablation may help to predict future recurrences.

BMP10 level helps to stratify risk of atrial fibrillation recurrence within one year after catheter ablation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): DGK Electrophysiology grant Background Freedom of atrial fibrillation (AF) is the main purpose of catheter ablation. However, AF recurrence is commonly seen after catheter ablation. Cardiovascular biomarkers may help to identify patients at risk for AF recurrence. Purpose We investigated the association of preprocedural known and novel cardiovascular biomarker level with AF recurrence within one year after catheter ablation. Methods In 187 patients of the AFAB registry (University Maastricht, the Netherlands) clinical recurrence of AF after catheter ablation was investigated using Holter ECGs at 3- and 12-months follow-up. Blood samples taken before AF catheter ablation were analyzed for prediction of AF recurrence by known or novel cardiovascular biomarkers (FGF23, BMP10, Ang2, IGFBP7, CA125, NT-proBNP, TNT_hs, sFlt_1, ESM1_7F89A5, DKK3). Recurrence of AF was defined as any symptomatic, or ECG documented episode of AF within one year after catheter ablation. A logistic regression model adjusted for typical risk factors of AF recurrence (Sex, age, type of AF (paroxysmal or persistent), ongoing rhythm, LA diameter, heart failure, body mass index and hypertension) was calculated and receiver-operating analysis was performed for prediction of AF recurrence. Results AF recurrence was found in 86 patients within one year after catheter ablation. Elevated biomarker level in patients with AF recurrence were found for BMP10, Ang2, and NT-proBNP in univariate analysis (table 1). In the logistic regression BMP10 (Odds ratio 2.94, 95%CI 1.089-7.939, P=0.033) indicated a high probability of AF recurrence within one year. A model including factors of AF recurrence showed a predictability for AF recurrence of an area under the curve (AUC) of 0.68 (sensitivity 60%, specificity 64%). By adding each of the univariate significant biomarker the predictability of the model increases further Ang2 (AUC 0.69, sensitivity 69%, specificity 60%), NT-proBNP (AUC 0.69, sensitivity 65%, specificity 60%), and BMP10 (AUC 0.71, sensitivity 60%, specificity 73%). Conclusions Based on our data, Ang2, BMP10, NT-proBNP showed elevated values for patients with recurrence of AF within one year before catheter ablation. BMP10, which is likely associated with trabeculation of the heart, outperformed the other investigated known and novel biomarker indicating a higher probability of AF recurrence within one year after ablation.

Elevation of Preprocedural Systemic Immune Inflammation Level Increases the Risk of Contrast-Associated Acute Kidney Injury Following Coronary Angiography: A Multicenter Cohort Study.

BackgroundInflammation and immune responses play an important role in the pathophysiology of contrast-associated acute kidney injury (CA-AKI), and systemic immune inflammation index (SII) has recently emerged as a new parameter for immune and inflammatory response evaluation. However, limited research has been undertaken to explore the relationship between SII and CA-AKI following coronary angiography (CAG).Patients and MethodsFrom January 2007 to December 2020, 46,333 patients undergoing CAG were included from 5 Chinese tertiary hospitals. SII was calculated as total peripheral platelets count × neutrophil-to-lymphocyte ratio. Patients were categorized by preprocedural SII quartiles: Q1 ≤404.5, Q2 >404.5 and ≤631.7, Q3 >631.7 and ≤1082.8, Q4 >1082.8. Univariable and multivariable logistic regression were used to reveal the link between preprocedural SII and CA-AKI.ResultsA total of the 46,333 patients (62.9 ± 11.5 years, female 28.1%) were included in the study. The incidence of CA-AKI was 8.4% in Q1 group, 8.7% in Q2 group, 9.4% in Q3 group, 15.1% in Q4 group. In the multivariable model, comparing the highest (Q4 group) to lowest (Q1 group) SII level categories, preprocedural SII was related to a higher risk of CA-AKI after fully adjusting for well-known confounders, and there was no statistically difference in the other two SII level categories (Q2 and Q3 groups) compared with Q1 group (adjusted model 3: Q2 group: OR: 0.98, 95% CI: 0.87–1.11, P = 0.771; Q3 group: OR: 1.04, 95% CI: 0.92–1.18, P = 0.553; Q4: OR: 1.65, 95% CI: 1.45–1.88, p < 0.001; P for trend < 0.001). Similar results were found for all the subgroups analysis except for patients undergoing PCI, and the interaction analyses for age, PCI and AMI were significant. In addition, Kaplan–Meier curves demonstrated that the lowest quartile group showed the worst all-cause mortality in a significant SII level-dependent manner among the four groups (Log rank test; p < 0.0001).ConclusionElevated preprocedural SII level was a significant and independent risk factor for CA-AKI following CAG. Higher-quality prospective studies are needed to validate the predictive value of SII for CA-AKI.

Predictive Value of Soluble Growth Stimulator Gene 2 Protein for Coronary Slow Flow/No-Reflow in ST-Elevation Myocardial Infarction Patients Receiving Percutaneous Coronary Intervention

Background Soluble growth stimulator gene 2 protein (sST2) is associated with heart failure and myocardial infarction; however, the predictive value of plasma sST2 level for coronary slow flow/no-reflow (CSF/NRF) is unclear. This study aimed to explore the predictive value of plasma sST2 levels for CSF/NRF in patients with ST-elevation myocardial infarction (STEMI) who underwent emergency percutaneous coronary intervention (PCI). Methods A total of 242 STEMI patients who underwent emergency PCI at our hospital between November 2020 and July 2021 were enrolled in this study. According to the postprocedural procedure, these patients were divided into the CSF/NRF and control groups. Clinical data were collected from both groups and were used to explore the predictive value of serum sST2 levels for CSF/NRF. Results Of the total 242 patients, CSF/NRF was observed in 50 patients (20.7%). Statistically significant differences (P < 0.05) were observed in age, diabetes mellitus, sST2 level, neutrophil-to-lymphocyte ratio (NLR), fasting blood sugar, preprocedural blood pressure, intraprocedural hypotension, N-terminal pro-B-type natriuretic peptide, MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTNI). Multivariate analysis showed that the sST2 level, NLR, and intraoperative hypotension were independent risk factors for CSF/NRF. ROC curve analysis showed that the sensitivity and specificity of the sST2 level for predicting CSF/NRF were 68.0% and 75.5%, respectively, when the sST2 level was more than 64.6 ng/mL (AUC = 0.780, 95% CI: 1.003–1.020, P=0.009). Conclusion For STEMI patients, preprocedural sST2 levels significantly correlated with CSF/NRF occurring in PCI. sST2 level is a potential predictor for CSF/NRF occurrence.

Risk stratification using growth differentiation factor 15 in patients undergoing transcatheter aortic valve implantation.

Growth differentiation factor 15 (GDF15) shows potential predictive value in various cardiac conditions. We investigated relationships between GDF15 and clinical or procedural outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) in order to propose clinically useful predictive risk stratification model. This prospective single-center registry enrolled 88 consecutive patients with severe symptomatic aortic stenosis treated with TAVI. Clinical parameters were collected and biomarkers including GDF-15 were measured within 24 h before TAVI. All relevant clinical outcomes according to the Valve Academic Research Consortium-2 were collected over the follow-up period. The cohort included 52.3% of females. The mean age of study participants was 81 years; the mean Society of Thoracic Surgeons (STS) score and logistic EuroSCORE were 3.6% and 15.4%, respectively. The mortality over the entire follow-up period was 10.2%; no death was observed within the first 30 days following TAVI. Univariate analysis showed significant associations between GDF15 and mortality (P=0.0006), bleeding (P=0.0416) and acute kidney injury (P=0.0399). A standard multivariate logistic regression model showed GDF-15 as the only significant predictor of mortality (P=0.003); the odds ratio corresponding to an increase in GDF15 of 1000 pg/mL was 1.22. However, incremental predictive value was not observed when the STS score was combined with GDF15 in this predictive model. Based on our observations, preprocedural elevated GDF15 levels are associated with increased mortality and demonstrate their additional value in predicting adverse clinical outcomes in a TAVI population.

Low Circulating Musclin is Associated With Adverse Prognosis in Patients Undergoing Transcatheter Aortic Valve Implantation at Low-Intermediate Risk.

BackgroundMusclin is an activity‐stimulated and cardioprotective myokine that attenuates pathological cardiac remodeling. Musclin deficiency, in turn, results in reduced physical endurance. The aim of this study was to assess the prognostic value of circulating musclin as a novel, putative biomarker to identify patients undergoing transcatheter aortic valve implantation (TAVI) who are at a higher risk of death.Methods and ResultsIn this study, we measured systemic musclin levels in 368 patients undergoing TAVI who were at low to intermediate clinical risk (median EuroSCORE [European System for Cardiac Operative Risk Evaluation] II: 3.5; quartile 1–quartile, 2.2%–5.3%), whereby 209 (56.8%) patients were at low and 159 (43.2%) were at intermediate risk. Median preprocedural musclin levels were 2.7 ng/mL (quartile 1–quartile 3, 1.5–4.6 ng/mL). Musclin levels were dichotomized in low (<2.862 ng/mL, n=199 [54.1%]) or high (≥ 2.862 ng/mL, n=169 [45.9%]) groups using cutoff values determined by classification and regression tree analysis. The primary end point was 1‐year overall survival. Patients with low circulating musclin levels exhibited a significantly higher prevalence of frailty, low albumin values, hypertension, and history of stroke as well as higher N‐terminal pro‐B‐type natriuretic peptide. Low musclin levels significantly predicted risk of death in univariable (hazard ratio, 1.81; 95% CI, 1.00–3.53 [P=0.049]) and multivariable (adjusted hazard ratio, 2.45; 95% CI, 1.06–5.69 [P=0.037]) Cox regression analyses. Additionally, low musclin levels in combination with conventional EuroSCORE II suggested improved risk stratification in patients undergoing TAVI who were at low to intermediate clinical risk into subgroups with reduced 1‐year survival rates by log‐rank test (P for trend=0.003).ConclusionsCirculating musclin is an independent predictor of 1‐year overall survival in patients undergoing TAVI. Combined with EuroSCORE II, circulating musclin might help to improve prediction of mortality in patients undergoing TAVI who are at low to intermediate clinical risk.

Effect of Bronchoscopist-Directed Sedation and Other Factors on Patient Comfort during Diagnostic Flexible Bronchoscopy.

Background The factors affecting patient comfort during flexible bronchoscopy are not sufficiently addressed in resource-limited countries, and a need to devise strategies to improve patient experience is felt. The present study was undertaken to assess the effect of sedation and other factors on patient comfort during flexible bronchoscopy. Methods A total of 374 patients, aged ≥18 years undergoing flexible bronchoscopy, were enrolled in this prospective, single-center, cross-sectional study. The baseline clinical data of sedation and nonsedation groups were recorded. Anxiety level was assessed using Visual Analog Scale (VAS). Postprocedure VAS score (primary outcome measure) assessed the discomfort related to flexible bronchoscopy. Patient-reported willingness for a repeat procedure and occurrence of adverse events were used as secondary outcome measures. Based on the median of VAS score, the study population was divided into low discomfort and high discomfort groups, and the factors affecting comfort levels in these two groups were noted. Results Postprocedural VAS score (median (Q1, Q3)) for sedation and nonsedation groups was 20 (15, 30) and 25 (20, 40), respectively (<0.001). Willingness for a repeat procedure was significantly more in the sedation group (p=0.002). In the low and high discomfort groups, the preprocedural anxiety level (median (Q1, Q3)) was 20 (10, 25) and 30 (20, 40), respectively (p < 0.001). Conclusion Bronchoscopist-directed sedation significantly reduces patient discomfort and increases their willingness for a repeat procedure. Midazolam-fentanyl combination and lower prebronchoscopy anxiety are associated with lower discomfort levels during flexible bronchoscopy. This study is registered with the Clinical Trial Registry of India (CTRI/2018/11/016328).

Association of serum laboratory parameters with periprocedural myocardial infarction after a primary percutaneous coronary intervention.

Periprocedural myocardial infarction (PMI) is one of the mortality-related complications of percutaneous coronary intervention (PCI) and significantly affects short- and long-term adverse outcomes and immediate cardiovascular events. Our present study aimed to evaluate the association of preprocedural serum laboratory parameters and PMI in patients who received primary PCI and attempted to provide detailed data on the predictors of PCI-related PMI. A total of 1184 consecutive coronary artery disease (CAD) patients who received primary and elective PCI between July 2015 and June 2017 were included and divided into control group and PMI group. The data of serum laboratory parameters were collected from the electronic database of Meizhou People's Hospital. The results indicated that preprocedural fasting blood glucose were higher in PMI group compared with the control group (p < .001). Patients with prior hyperlipidemia were more likely to have experienced PCI-related PMI (p = .018) and the preprocedural level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, apolipoprotein B (Apo B), and LDL-C/high density lipoprotein cholesterol (HDL-C) were significantly enhanced in PMI group (p < .001). Multivariate regression analysis revealed that preprocedural fasting blood glucose > 6.11mmol/L (p < .001, OR = 1.949, 95% CI: 1.444-2.630) and LDL-C levels ≥130mg/dL (p = .005, OR = 1.941, 95% CI: 1.217-3.098) independently predicted PCI-related PMI. Our results indicated preprocedural fasting blood glucose >6.11mmol/L and LDL-C levels ≥130mg/dL may be useful predictors for PCI-related PMI. The study may provide a detailed data on the predictors of PCI-related PMI.

Effectiveness of Virtual Reality for Pediatric Pain and Anxiety Management during Skin Prick Testing

This study investigated the effectiveness of virtual reality (VR) distraction, compared to comic book distraction and no distraction, in reducing pain and anxiety during a medical procedure in a pediatric population: the skin prick test. Although this test has many advantages and is considered to be minimally invasive, it causes anxiety and painful discomfort in children. Ninety-two children aged 7 to 17 years consulting for an allergic test received VR distraction, comic book distraction, or no distraction. Outcome measures included pain score, level of anxiety, and VR measures. The results showed that there were no significant differences between the three groups regarding sex, age, and preprocedural anxiety level. In the distraction groups (VR and comic book), children reported significantly lower pain and procedural anxiety scores than children with no distraction; VR distraction had a more significant effect than comic book distraction. A decrease in anxiety before and during the skin prick test is significantly more significant in VR distraction. This study suggested the effectiveness and feasibility of VR to reduce pain and anxiety during the pediatric skin prick test.

Vagal response during circumferential pulmonary vein isolation decreases the recurrence of atrial fibrillation in the short-term in patients with paroxysmal atrial fibrillation: A prospective, observational study

BackgroundVagal responses (VRs) are often seen in patients undergoing circumferential pulmonary vein isolation (CPVI). The possible mechanism of VR is that CPVI creates a coincidental modification of the cardiac ganglionated plexi (GP). AimTo investigate whether the presence of VR during CPVI impacts post-ablation recurrence in patients with paroxysmal atrial fibrillation (AF). MethodsA total of 112 consecutive patients with symptomatic paroxysmal AF who underwent CPVI for the first time from October 1, 2017 to April 30, 2019 were prospectively enrolled, of which two were lost the follow-up. Patients were divided into two groups based on whether VRs were experienced during CPVI. Electrophysiological parameters, including atrial effective refractory period (AERP) and mean heart rate (MHR), were measured before and post-ablation. The patients were then followed up for 12 months. ResultsThe 71 patients who had experienced VRs during CPVI were assigned to group B, and the remaing 39 patients who did not experience VR during CPVI were assigned to group A. The MHR (79.6 ± 8.3 vs 70.4 ± 7.8 b/min; p ≤ 0.001) was significantly higher; and the AERP (244 ± 22 vs 215 ± 27 ms; p ≤ 0.001) was prolonged in group B compared to respective pre-ablation values. There were no significant changes in the MHR (69.5 ± 7.9 vs 69.7 ± 8.7 b/min; p = 0.541) and AERP (224 ± 28 vs 225 ± 33 ms; p = 0.542) in group A. During the first four months of follow-up after ablation, the MHR gradually slowed down to pre-procedural levels in group B. The recurrence of AF (6/71 vs 7/39; p = 0.023) significantly decreased in group B relative to group A during the first 6 months after ablation, but there was no significant difference (14/71 vs 9/39; p = 0.598) at the end of the 12-month follow-up period. ConclusionPatients with paroxysmal AF who develop VRs during CPVI might have a decreased recurrence of AF and accelerated MHR in the short-term.

Impact of albumin on the incidence of adverse events following percutaneous coronary interventions in older adults

Abstract Background Recent studies have focused on comorbidities or frailty as predictors of adverse events in older adults undergoing percutaneous coronary interventions (PCI), however the prognostic impact of nutritional parameters has been less extensively studied. Purpose Our objective was to analyze the impact of serum albumin on the incidence of adverse events after PCI in older patients. Methods We conducted a prospective observational study of all-corner consecutive patients aged ≥75 years submitted for PCI at our institution from 2014 to 2017, and with available pre-procedural serum albumin levels. We analyzed the distribution of albumin levels in such population, and the impact of hypoalbuminemia (albumin &amp;lt;3.5 g / dL) on 12-months cumulative incidence of MACE (cardiovascular death, myocardial infarction or stroke), BARC types 3 or 5 major bleeding, and all-cause death. Results Study population comprised 169 patients (mean age 82±5 years, 38% women). Mean albumin level was 3.8±0.5 g/dL, and 23% showed levels &amp;lt;3.5 g/dL. Hypoalbuminemia was associated with only mild impairments in baseline cardiac or renal function. During the 12-month follow-up, albumin levels were not associated with a higher incidence of MACE (log-rank p=0.22) but they were associated with a higher incidence of bleeding (22.4% vs. 8.0%, p=0.014), and with all-cause mortality (20.5% vs. 6.2%, p=0.006). Albumin revealed an independent and greater impact than bleeding scores, anemia or discharge anticoagulation on the prediction of bleeding (adjusted HR 2,88, p=0.028). Conclusions Albumin levels confer relevant prognostic information that should be assessed in older adults receiving PCI. The effect on bleeding is independent of other well-established variables. Systematic quantification of this widely available parameter may be helpful for clinical decision-making. Funding Acknowledgement Type of funding sources: None. Figure 1. Hypoalbuminemia and all-cause death

Circulating microRNA-122-5p correlates with improvement in left-ventricular function after transcatheter aortic valve replacement and regulates viability of cardiomyocytes via extracellular vesicles

Abstract Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis (AVS). However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Herein, we generally explored the differential expression of miRNAs in circulating extracellular vesicles (EV-miRNAs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes. Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in aortic stenosis patients at day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122 were negatively correlated with LVEF improvement at both day seven (r=−0.264 and p=0.015) and at six months (r=−0.328 and p=0.0018) after TAVR. At the three-year follow-up, patients with a higher level of miR-122-5p displayed significantly increased cardiovascular mortality (p=0.03). By utilization of patient-derived samples and a murine aortic-stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced aortic-valve-stenotic mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells in comparison to cardiomyocytes. Co-culture experiments with endothelial cells and cardiomyocytes, copy-number analysis, fluorescence microscopy with Cy3-labeled miR-122-5p demonstrated that miR-122-5p can be shuttled via large extracellular vesicles from endothelial cells into cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes and regulates viability of the cardiomyocytes. In silico prediction and mass spectrometry were used to search for binding partners of miR-122-5p. Mechanistically, miR pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation confirmed that miR-122-5p interacts with an RNA-binding protein, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling into recipient cells, miR-122-5p negatively regulates the expression of the anti-apoptotic gene BCL2, by binding to its 3' untranslated region to regulate its translation, and thereby decreasing the viability of target cardiomyocytes. Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p is associated with reduced LVEF after TAVR. Extracellular vesicular shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a Bcl2-dependent manner. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Research Foundation (DFG); German Society of Cardiology (DGK)

Prognostic Significance of Preprocedural N-Terminal Pro-B-Type Natriuretic Peptide Assessment in Diabetic Patients With Multivessel Coronary Disease Undergoing Revascularization.

Background and Aims: The N-terminal pro-B-type natriuretic peptide (NT-proBNP) may predict adverse cardiovascular outcomes in patients with diabetes. However, its prognostic value in patients with multivessel disease (MVD) undergoing coronary revascularization remains unclear. This study aimed to evaluate the prognostic significance of preprocedural NT-proBNP levels in diabetic patients with MVD undergoing coronary revascularization.Methods: A total of 886 consecutive diabetic patients with MVD who underwent coronary revascularization were enrolled in this study. Patients were divided into quartiles according to their pre-procedural NT-proBNP levels. Kaplan-Meier curves and Cox regression analyses were performed to evaluate the risk of cardiovascular events, including all-cause death, cardiovascular death, myocardial infarction (MI), stroke, and major adverse cardiovascular events (MACE), according to the NT-proBNP quartiles.Results: During a median follow-up period of 4.2 years, 111 patients died (with 82 being caused by cardiovascular disease), 133 had MI, 55 suffered from stroke, and 250 experienced MACE. Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of all-cause death, cardiovascular death, MI, and MACE (log-rank test, P < 0.001, respectively). Multivariate Cox regression analysis revealed that NT-proBNP level was an independent predictor of adverse outcomes, including all-cause death (HR, 1.968; 95% CI, 1.377–2.812; P < 0.001), cardiovascular death (HR, 1.940; 95% CI, 1.278–2.945; P = 0.002), MI (HR, 1.722; 95% CI, 1.247–2.380; P = 0.001), and MACE (HR, 1.356; 95% CI, 1.066–1.725; P = 0.013). The role of NT-proBNP in predicting adverse outcomes was similar in patients with stable angina pectoris and acute coronary syndrome. Moreover, preprocedural NT-proBNP alone discriminated against the SYNTAX II score for predicting all-cause death [area under the curve (AUC), 0.662 vs. 0.626, P = 0.269], cardiovascular death (AUC, 0.680 vs. 0.622, P = 0.130), MI (AUC, 0.641 vs. 0.579, P = 0.050), and MACE (AUC, 0.593 vs. 0.559, P = 0.171). The addition of NT-proBNP to the SYNTAX II score showed a significant net reclassification improvement, integrated discrimination improvement, and improved C-statistic (all P < 0.05).Conclusion: NT-proBNP levels were an independent prognostic marker for adverse outcomes in diabetic patients with MVD undergoing coronary revascularization, suggesting that preprocedural NT-proBNP measurement might help in the risk stratification of high-risk patients.

The Relationship between Elevated Pre-procedural Random Blood Glucose Level and Periprocedural Myocardial Injury in Patients Undergoing Elective Percutaneous Coronary Intervention

Abstract Background Regardless of the diabetic status of patients with coronary artery disease, both hyperglycemia and hypoglycemia are adversely associated with cardiovascular events. Numerous studies have concluded that hyperglycemia is common in diabetic and non-diabetic patients with STelevation myocardial infarction (STEMI) and is associated with a higher risk of death and in-hospital complications. Aim and Objectives The aim of this study is to assess the relationship between elevated preprocedural random blood glucose level and peri-procedural myocardial injury in patients undergoing elective percutaneous coronary intervention. Patients and Methods This Cohort study included 110 patients who presented with chronic coronary syndrome to the cardiology department of Ain Shams university hospitals and underwent elective PCI. They were divided into 2 equal groups, 55 as hyperglycemic group and 55 as euglycemic group. Blood glucose level was measured immediately before the procedure. Blood samples for cardiac troponin (I) were obtained before the procedure and 12 hours after the procedure. Results There was statistically significant difference between the two groups regarding incidence of both myocardial infarction and myocardial injury, both being higher among the hyperglycemic group (P-value: 0.022) &amp;(P-value: 0.001) respectively. All five patients who had myocardial infarction belonged to the hyperglycemic group. 23 patients with myocardial injury belonged to the hyperglycemic group while only 7 patients with myocardial injury belonged to the euglycemic group. Conclusion We conclude that abnormally high pre-procedural plasma glucose levels in patients undergoing coronary angioplasty are associated with an increased incidence of peri-procedural myocardial injury and infarction in patients undergoing elective PCI.