Mm Hg Mean Research Articles

CharActeristics, sizing anD outcomes of stenotic, tapered, rapHe-type bicuspid aOrtic valves treated with trans-catheter device implantation: Insights the AD HOC registry

BackgroundRaphe-type bicuspid aortic valve (BAV) is a potential hostile scenario in trans-catheter aortic valve replacement (TAVR) due to pronounced calcium burden, possibly associated with tapered valve configuration. Trans-Catheter heart valve (THV) sizing strategy (annular vs. supra-annular) is controversial in this valve subtype. ObjectivesTo describe the phenotypical characteristics of severe, tapered, raphe-type, BAV stenosis undergoing TAVR and to explore safety and efficacy of modern-generation THVs, analysing the impact of annular and supra-annular sizing strategies on short- and mid-terms outcomes. MethodsThis is a retrospective, multicenter registry enrolling consecutive stenotic Sievers type 1 BAV treated with TAVR. Study population was divided into tapered and non-tapered configuration according to MSCT analysis. Matched comparison between annular and supra-annular sizing groups was performed in tapered population. ResultsFrom January 2016 to June 2023, 897 patients were enrolled. Of them, 696 patients displayed a tapered configuration. Of those, 510 received a THV according to annular sizing. After propensity score matching 186 matched pairs were selected. Technical success (96.2 % vs 94.1 %, OR 1.61 [0.61–4.24], p = 0.34), 30-day device success (83.6 % in both groups, OR 1.42 [0.78–2.57], p = 0.25) and 30-day early safety (71.8 % vs 70.5 %, OR 1.07 [0.68–1.68], p = 0.78) were similar between the annular and supra-annular sizing groups; a higher post-TAVR gradient was observed in supra-annular group, although it was only 2 mmHg mean. At mid-term follow-up, the rate of clinical efficacy was 84.7 %. ConclusionsTAVR with modern-generation devices is safe and effective for tapered raphe-type BAV, showing comparable results for annular and supra-annular sizing strategies.

Association between Transient-Continuous Hypotension during Mechanical Thrombectomy for Acute Ischemic Stroke and Final Infarct Volume in Patients with Proximal Anterior Circulation Large Vessel Occlusion.

Background/Objectives: Periprocedural blood pressure changes in stroke patients with a large vessel occlusion are a known modifiable risk factor of unfavorable treatment outcomes. We aimed to evaluate the association between pre-revascularization hypotension and the final infarct volume. Methods: In our retrospective analysis, we included 214 consecutive stroke patients with an anterior circulation large vessel occlusion that underwent mechanical thrombectomy under general anesthesia. Noninvasively obtained blood pressure values prior to symptomatic vessel recanalization were analyzed as a predictor of post-treatment infarct size. Linear logistic regression models adjusted for predefined factors were used to investigate the association between blood pressure parameters and the final infarct volume. Results: In our cohort, higher baseline systolic blood pressure (aβ = 8.32, 95% CI 0.93-15.7, p = 0.027), its maximal absolute drop (aβ = 6.98, 95% CI 0.42-13.55, p = 0.037), and >40% mean arterial pressure decrease (aβ = 41.77, CI 95% 1.93-81.61, p = 0.040) were independently associated with higher infarct volumes. Similarly, continuous hypotension measured as intraprocedural cumulative time spent below either 100 mmHg (aβ = 3.50 per 5 min, 95% CI 1.49-5.50, p = 0.001) or 90 mmHg mean arterial pressure (aβ = 2.91 per 5 min, 95% CI 0.74-5.10, p = 0.010) was independently associated with a larger ischemia size. In the subgroup analysis of 151 patients with an M1 middle cerebral artery occlusion, two additional factors were independently associated with a larger ischemia size: systolic blood pressure maximal relative drop and >40% drop from pretreatment value (aβ = 1.36 per 1% lower than baseline, 95% CI 0.04-2.67, p = 0.043, and aβ = 43.01, 95% CI 2.89-83.1, p = 0.036, respectively). No associations between hemodynamic parameters and post-treatment infarct size were observed in the cohort of intracranial internal carotid artery occlusion. Conclusions: In patients with ischemic stroke due to a proximal middle cerebral artery occlusion, higher pre-thrombectomy treatment systolic blood pressure is associated with a larger final infarct size. In patients treated under general anesthesia, hypotension prior to the M1 portion of middle cerebral artery recanalization is independently correlated with the post-treatment infarct volume. In this group, every 5 min spent below the mean arterial pressure threshold of 100 mmHg is associated with a 4 mL increase in ischemia volume on a post-treatment NCCT. No associations between blood pressure and final infarct volume were present in the subgroup of patients with an intracranial internal carotid artery occlusion.

Percutaneous mechanical thrombectomy in acute pulmonary embolism: Outcomes from a safety-net hospital.

Our study aims to present clinical outcomes of mechanical thrombectomy (MT) in a safety-net hospital. This is a retrospective study of intermediate or high-risk pulmonary embolism (PE) patients who underwent MT between October 2020 and May 2023. The primary outcome was 30-day mortality. Among 61 patients (mean age 57.6 years, 47% women, 57% Black) analyzed, 12 (19.7%) were classified as high-risk PE, and 49 (80.3%) were intermediate-risk PE. Of these patients, 62.3% had Medicaid or were uninsured, 50.8% lived in a high poverty zip code. The prevalence of normotensive shock in intermediate-risk PE patients was 62%. Immediate hemodynamic improvements included 7.4 mmHg mean drop in mean pulmonary artery pressure (-21.7%, p < 0.001) and 93% had normalization of their cardiac index postprocedure. Thirty-day mortality for the entire cohort was 5% (3 patients) and 0% when restricted to the intermediate-risk group. All 3 patients who died at 30 days presented with cardiac arrest. There were no differences in short-term mortality based on race, insurance type, citizenship status, or socioeconomic status. All-cause mortality at most recent follow up was 13.1% (mean follow up time of 13.4 ± 8.5 months). We extend the findings from prior studies that MT demonstrates a favorable safety profile with immediate improvement in hemodynamics and a low 30-day mortality in patients with acute PE, holding true even with relatively higher risk and more vulnerable population within a safety-net hospital.

Effect of Sinotubular Junction Size on TAVR Leaflet Thrombosis: A Fluid-Structure Interaction Analysis.

TAVR has emerged as a standard approach for treating severe aortic stenosis patients. However, it is associated with several clinical complications, including subclinical leaflet thrombosis characterized by Hypoattenuated Leaflet Thickening (HALT). A rigorous analysis of TAVR device thrombogenicity considering anatomical variations is essential for estimating this risk. Clinicians use the Sinotubular Junction (STJ) diameter for TAVR sizing, but there is a paucity of research on its influence on TAVR devices thrombogenicity. A Medtronic Evolut® TAVR device was deployed in three patient models with varying STJ diameters (26, 30, and 34mm) to evaluate its impact on post-deployment hemodynamics and thrombogenicity, employing a novel computational framework combining prosthesis deployment and fluid-structure interaction analysis. The 30mm STJ patient case exhibited the best hemodynamic performance: 5.94mmHg mean transvalvular pressure gradient (TPG), 2.64 cm2 mean geometric orifice area (GOA), and the lowest mean residence time (TR)-indicating a reduced thrombogenic risk; 26mm STJ exhibited a 10 % reduction in GOA and a 35% increase in mean TPG compared to the 30mm STJ; 34mm STJ depicted hemodynamics comparable to the 30mm STJ, but with a 6% increase in TR and elevated platelet stress accumulation. A smaller STJ size impairs adequate expansion of the TAVR stent, which may lead to suboptimal hemodynamic performance. Conversely, a larger STJ size marginally enhances the hemodynamic performance but increases the risk of TAVR leaflet thrombosis. Such analysis can aid pre-procedural planning and minimize the risk of TAVR leaflet thrombosis.

Targeting liver angiotensinogen using a GalNAc-siRNA improves cardiac remodeling in spontaneously hypertensive rats

Abstract Background Dysregulation of the Renin-Angiotensin-Aldosterone System (RAAS) leads to hypertension and cardiac hypertrophy. Angiotensinogen (AGT) is the only precursor of all angiotensin peptide products. Liver-specific AGT silencing has been proven to be a promising treatment option in lowering blood pressure (BP) in patients, characterized by full RAAS inhibition and little RAAS escape phenomena. However, the long-term effects of AGT knockdown on cardiac remodeling is still unclear. Purpose To explore the long-term effects of a GalNAc-conjugated siRNA drug R0797070 on AGT inhibition, BP and cardiac functions in Spontaneously Hypertensive Rats (SHRs). Methods In vitro inhibitory activities of siRNAs were assessed in primary rat hepatocytes. The selected siRNA was conjugated with GalNAc based on RIBO-GALSTAR liver targeting system and named R0797070. In vivo effects of repeated doses of R0797070 were evaluated in SHR model. The animals were treated with R0797070 (3 mg/kg, every 8 weeks; subcutaneous injection) or PBS (5 ml/kg, every 8 weeks; subcutaneous injection) for 7 months with the first dose (day1) at the 3 months of age. Captopril (100 mg/kg per day; oral administration) was taken as a positive drug control and Wistar rats were used as normotensive control group. Blood pressure was monitored by tail-cuff method after an initial acclimatization training period. Serum AGT protein was measured by ELISA and liver mRNA expression was detected by qPCR. Echocardiography was used to determine the changes of cardiac morphology and functions，and wheat germ agglutinin (WGA) staining was used to measure myocyte cross-sectional size. Results R0797070 showed 90-99% inhibitory activities on hepatic AGT mRNA at different doses. In SHRs, a single dose of R0797070 at 3 mg/kg resulted in a maximum inhibition of 97% for serum AGT protein with 27 mmHg mean blood pressure (MBP) reduction on Day 15. Daily administration of Captopril could reduce MBP by 33 mmHg on average, while the duration of drug efficacy of R0797070 could reach 2 months with the average 25 mmHg MBP reduction. At the end of study, the echocardiographic results showed that R0797070 significantly reduced left ventricular hypertrophy in the 10-month-old SHRs. Consistently, R0797070 treatment reduced the heart weight by 10%，and LV myocyte size by 17%. Conclusion We showed the long-term effects of a GalNAc-siRNA R0797070 on silencing angiotensinogen expression, reducing blood pressure and left ventricular hypertrophy. Compared to daily oral administration of Captopril and its effect on blood pressure R0797070 demonstrated significant effect on cardiac hypertrophy.Figure 1Figure 2

Catheter-directed therapies impact on intermediate-high- and high-risk pulmonary embolism patients

Abstract Introduction Intermediate-high- and high-risk pulmonary embolism (PE) patients treated with anticoagulation alone are associated with a considerable risk of circulatory collapse, death, or long-term pulmonary hypertension. Pulmonary Embolism Response Teams (PERT) have been created to deliver PE patients a better care. Catheter Directed Therapies (CDT), with mechanical thrombolysis and/or local fibrinolysis allow faster reperfusion and hemodynamic improvement without the systemic hemorrhagic effects of systemic fibrinolysis. The clinical evidence of its benefits is lacking. Objectives This analysis aims to describe the hemodynamics, morphological and perfusion improvement in intermediate-high- and high-risk acute PE patients submitted to CDT. Methods Prospective registry of consecutive intermediate-high- and high-risk PE patients submitted to CDT (mechanical thrombolysis with PenumbraÔ aspiration system and/or intrapulmonary local fibrinolysis with alteplase) in a single tertiary center. A multiparametric follow-up protocol was designed to evaluate echocardiographic, CT-scan, pulmonary angiogram, and right heart catheterization data at admission and at 3 months after CDT. The paired samples t-Test was used for the analysis of the variables. Results 26 PE patients (42.3% male, mean age 59 years old) were submitted to CDT (19% combined Penumbra and local fibrinolysis, 12% isolated Penumbra and 69% isolated local fibrinolysis). Baseline characteristics, laboratorial, imaging and procedure data are summarized in the figure 1. No major bleeding was seen during or after the procedure. 1 pulmonary artery dissection and 1 Penumbra burr partial avulsion occurred, both with conservative treatment with good result. 3 patients died during the follow-up (1 for oncologic disease, 1 for septic shock and 1 after discharge with undetermined cause). Of the remaining, 18 patients completed the 3-month follow-up protocol. At 3 months, a significant improvement was seen in the patients’ hemodynamics with 3.3mmHg mean drop of RA pressure (p 0.007), 16.1mmHg mean drop of systolic PA pressure (p &amp;lt;0.001), 8.0mmHg mean drop of mean PA pressure (p&amp;lt;0.001), 1.4L/min and 0.7L/min/m2 mean increases in cardiac output and index (p 0.003, p 0.001), and a tendency to a 0.8 Wood units decrease in the pulmonary vascular resistance (p 0.093). It was also seen an improvement in the perfusion defects with a mean drop of 7.9 points in the modified Miller index (p &amp;lt;0.001) and an improvement in the RV function with a mean decrease of 0.5 in the RV/LV ratio by CT-scan (p &amp;lt;0.001), a mean increase of 5.6mm in TAPSE (p &amp;lt;0.001) and a decrease of median NT-proBNP levels in 2866pg/ml (p &amp;lt;0.001). Conclusions In patients with intermediate-high- and high-risk PE, the use of CDT with mechanical thrombolysis and/or local fibrinolysis is safe and associated with improvement in hemodynamics, RV function and perfusion defects.Table 1.baseline characteristicsTable 2.results

Abstract P342: Acute Nasal Breathing Lowers Blood Pressure And Increases Parasympathetic Contributions To Heart Rate Variability In Young Adults

Introduction: Interest is growing in how breathing pace, pattern, and training (e.g., device-assisted or -resisted breathing) affect prognostic cardiovascular variables (e.g., blood pressure (BP)). Nasal breathing increases bronchodilation via airway epithelium nitric oxide production, increases diaphragmatic movement, and reduces accessory inspiratory muscle recruitment. Despite these changes, the effect of nasal compared with oral breathing (i.e., breathing route) on prognostic cardiovascular variables is unclear. Hypothesis: We hypothesized that nasal compared with oral breathing would acutely lower BP and improve heart rate variability (HRV) metrics. Methods: We tested 20 young healthy adults in this study (13 Female/7 Male; age: 18 [1] years, median [IQR]; body mass index: 23 ± 2 kg•m -2 , screening systolic / diastolic BP 116 ± 12 / 67 ± 7 mmHg mean ± SD). Participants self-selected their breathing rate during a five-minute ‘run-in’ period. Using a metronome, their breathing rate was fixed during two subsequent (random order) five-minute resting periods with nasal and oral breathing while we measured brachial BP and HRV metrics via ECG. We compared data between conditions using a Wilcoxon signed-rank paired test (data presented as median [IQR]) or using paired, two-tailed t-tests (data presented as mean ± SD). We set the significance to p &lt;0.05. Results: Nasal breathing lowered mean (nasal: 84 ± 7 vs. oral: 86 ± 5 mmHg, p =0.006, Cohen’s d =0.70) and diastolic (nasal: 68 [8] vs. oral: 72 [5] mmHg, p &lt;0.001, Rank-biserial correlation=0.89), but not systolic (nasal: 116 ± 11 vs. oral: 117 ± 9 mmHg, p =0.48, Cohen’s d =0.16) BP. Nasal breathing also raised the High-Frequency contribution to HRV (nasal: 59 ± 19 vs. oral: 52 ± 21 %, p =0.04, Cohen’s d =0.50) and lowered the Low-Frequency to High-Frequency ratio (nasal: 0.9 ± 0.8 vs. oral: 1.2 ± 0.9, p =0.04, Cohen’s d =0.49), suggesting a greater parasympathetic contribution to HRV. There were no differences between conditions for heart rate ( p= 0.90) or time-domain HRV metrics ( ps ≥0.07; e.g., the standard deviation of NN intervals). Conclusion: These data suggest that nasal compared with oral breathing acutely lowers mean and diastolic BP as well as potentially increases parasympathetic contributions to HRV.

Effect of leisure-time physical activity on blood pressure in people with hypertension: a systematic review and meta-analysis

High blood pressure is a major risk factor for premature death. Leisure-time physical activities have been recommended to control hypertension. Studies examining how leisure-time physical activity affects blood pressure have found mixed results. We aimed to conduct a systematic review examining the effect of leisure-time physical activity (LTPA) on lowering blood pressure among adults living with hypertension. We searched studies in Embase, Medline/PubMed, Web of Science, Physical Education Index, Scopus and CENTRAL (the Cochrane Library). The primary outcome variables were systolic blood pressure (SBP) and diastolic blood pressure (DBP). This systematic review is registered on PROSPERO (CRD42021260751). We included 17 studies out of 12,046 screened articles in this review. Moderate-intensity LTPA (all types) reduced SBP compared to the non-intervention control group (MD −5.35 mm Hg, 95% CI −8.06 to −2.65, nine trials, n = 531, low certainty of the evidence). Mean DBP was reduced by −4.76 mm Hg (95% CI −8.35 to −1.17, nine trials, n = 531, low certainty of the evidence) in all types of LTPA (moderate intensity) group compared to the non-intervention control group. Leisure-time walking reduced mean SBP by −8.36 mmHg, 95% CI −13.39 to −3.32, three trials, n = 128, low certainty of the evidence). Walking during leisure time reduced −5.03 mmHg mean DBP, 95% CI −8.23 to −1.84, three trials, n = 128, low certainty of the evidence). Performing physical activity during free time probably reduces SBP and DBP (low certainty of the evidence) among adults with hypertension.

Quick Assessment of the Lower Limit of Cerebral Autoregulation Using Transcranial Doppler during Cardiopulmonary Bypass in Cardiac Surgery: A Feasibility Study.

During cardiac surgery, maintaining a mean arterial pressure (MAP) within the range of cerebral autoregulation (CA) may prevent postoperative morbidity. The lower limit of cerebral autoregulation (LLA) can be determined using the mean velocity index (Mx). The standard Mx is averaged over a ten second period ( ) while using a two second averaging period ( ) is faster and may record more rapid variations in LLA. The objective of this study is to compare a quick determination of LLA (qLLA) using with the reference LLA (rLLA) using . Single center, retrospective, observational study. Patients undergoing cardiac surgery with cardiopulmonary bypass. From January 2020 to April 2021, perioperative transcranial doppler measuring cerebral artery velocity was placed on cardiac surgery patients in order to correlate with continuous MAP values. Calculation of each patient's Mx was manually determined after the surgery and qLLA and rLLA were then calculated using a threshold value of Mx 0.4. 55 patients were included. qLLA was found in 78% of the cases versus 47% for rLLA. Despite a -3 mmHg mean bias, limits of agreement were large [-19 mmHg (95% CI: -13; -25), and +13 mmHg (95% CI: +6; +19)]. There was an important interobserver variability (kappa rLLA = 0.46; 95% CI: 0.24-0.66; and Kappa qLLA = 0.36; 95% CI: 0.20-0.52). Calculation of qLLA is feasible. However, the large limits of agreement and significant interobserver variability prevent any clinical utility or interchangeability with rLLA.

Acute outcomes for the full US cohort of the FLASH mechanical thrombectomy registry in pulmonary embolism.

Evidence supporting interventional pulmonary embolism (PE) treatment is needed. We aimed to evaluate the acute safety and effectiveness of mechanical thrombectomy for intermediate- and high-risk PE in a large real-world population. FLASH is a multicentre, prospective registry enrolling up to 1,000 US and European PE patients treated with mechanical thrombectomy using the FlowTriever System. The primary safety endpoint is a major adverse event composite including device-related death and major bleeding at 48 hours, and intraprocedural adverse events. Acute mortality and 48-hour outcomes are reported. Multivariate regression analysed characteristics associated with pulmonary artery pressure and dyspnoea improvement. Among 800 patients in the full US cohort, 76.7% had intermediate-high risk PE, 7.9% had high-risk PE, and 32.1% had thrombolytic contraindications. Major adverse events occurred in 1.8% of patients. All-cause mortality was 0.3% at 48-hour follow-up and 0.8% at 30-day follow-up, with no device-related deaths. Immediate haemodynamic improvements included a 7.6 mmHg mean drop in mean pulmonary artery pressure (-23.0%; p<0.0001) and a 0.3 L/min/m2 mean increase in cardiac index (18.9%; p<0.0001) in patients with depressed baseline values. Most patients (62.6%) had no overnight intensive care unit stay post-procedure. At 48 hours, the echocardiographic right ventricle/left ventricle ratio decreased from 1.23±0.36 to 0.98±0.31 (p<0.0001 for paired values) and patients with severe dyspnoea decreased from 66.5% to 15.6% (p<0.0001). Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes, and low 30-day mortality for intermediate- and high-risk PE.

The Study of Offspring and Mothers with Gestational Diabetes Treated with Metformin or Glibenclamide in a Randomized Controlled Trial after 9 Years

Introduction: Follow-up of the mothers and their offspring recruited to a randomized controlled trial comparing neonatal outcomes in women with gestational diabetes treated with metformin or glibenclamide was conducted 9 years ago. A significant decrease in neonatal hypoglycemia in the group treated with metformin was seen in the original study. Methodology: Results of clinical examination, blood sample collection, and dual-energy X-ray absorptiometry (DEXA) scan not published in a brief communication are described in this study. The nutritional status was assessed using a 3-day recall method using the Indian Food Composition Table 2017. The physical activity of offspring was assessed using the Global Physical Activity Questionnaire. Results: The overall follow-up rate of the cohort was 49% and similar in both the groups. The anthropometric details, blood tests, and DEXA in the women and their offspring were similar except that the offspring of the group on metformin had higher triglyceride values than the offspring of the women treated with glibenclamide. The average body mass index of the offspring was similar and was 18. Currently, women who were treated with glibenclamide 9 years ago had higher fasting plasma glucose levels (9.2 [7.3, 12.6]) than the metformin group (7.2 [6.1, 8.4] median [interquartile range]), P = 0.02. They also had significantly higher diastolic blood pressure readings 77.1mmHg (8.9) and 72.1mmHg (11.7) mean (SD), P = 0.035. (Information from the previously published brief communication). Conclusion: No significant adverse outcome was seen in women treated with metformin and the offspring 9 years later.

Co-existence of Obstructive and Septic Shock in a Patient Identified by Point of Care Ultrasonography: A Case Report

Shock is a state of acute circulatory failure leading to decreased organ perfusion, inadequate delivery of oxygenated blood to tissues, and resultant end-organ dysfunction. A 45-year-old male patient a known case of Diabetes Mellitus (DM) presented to the Emergency Room (ER) with a complaint of fever for four days and shortness of breath for one day. The patient had a wound discharging pus over the dorsum of the right foot for two weeks following trauma. On examination, the patient’s vitals were: pulse rate-88 Beats Per Minute (bpm), respiratory rate-26 breaths per minute, SpO2 -78% room air, Blood Pressure (BP)-82/40 mmHg mean arterial pressure- 54 mmHg. As a protocol of shock evaluation, Point Of Care Ultrasonography (POCUS) showed a distended Inferior Vena Cava (IVC), dilated right atrium and ventricle, and good left ventricular systolic function. Given the presence of right leg swelling, ultrasound was done, which showed a thrombus in the popliteal vein. Noradrenaline infusion was started to maintain a mean arterial blood pressure of 70 mmHg. A diagnosis of obstructive shock due to pulmonary embolism was strongly suspected, and thrombolysis with injection streptokinase was done. After two hours of thrombolysis, Two-Dimensional (2D) Echocardiography (ECHO) revealed normal right atrium and ventricle size and IVC collapsibility index of 70%, but the patient’s blood pressure didn’t improve significantly. So, adequate intravenous fluid was given as per the septic shock protocol. But, the noradrenalin requirement didn't improve. The patient was put on broad-spectrum antibiotics. Blood culture showed growth of Pseudomonas aeruginosa. So, a diagnosis of co-existing septic shock with obstructive shock was made. The patient improved and discharged in stable condition. The present case report highlights the co-existence of septic shock and obstructive shock and the usefulness of POCUS in differentiating and managing various shocks.

Modified and Novel Lorrca Oxygenscan Measurement Parameters with Physiological Relevance

BACKROUND: Despite arising from a single-point hemoglobin (Hb) mutation (βGlu6 replaced by valine), patients with sickle cell disease (SCD) display wide phenotype variation. This likely arises from sickling and its resulting pathology having multiple physiologic triggers, many of which are red blood cell (RBC) related, i.e., sickle hemoglobin (HbS) and fetal hemoglobin (HbF) concentration, membrane permeability, cell hydration, etc. These triggers are inadequately captured by single measurement parameters and require a more holistic functional RBC assessment (reflecting their composite effects). To provide such, oxygen (O2) gradient ektacytometry (LORRCA oxygenscan RR Mechatronics) was designed as a commercial, rapid, reproducible, and automated laboratory assay, which mimics in vivo physiology, quantifying RBC deformability across the physiological O2 gradient. This assay captures the process of sickling/unsickling of a RBC population when challenged with deoxygenation and reoxygenation. Significant variance in the oxygenscan point of sickling measurement was observed (POS - defined as the pO2at which EImax declined 5% - representing the initiation of sickling), despite following all guidelines for sample handling. EI fluctuation at higher O2 partial pressure (pO2) was noted as the cause for this. We consequently modified the POS determination, centering our analysis on EI rate of change (i.e., the first derivative of the EI trace), rather than the single point software determination. We further identified two new analyses parameters which reflect aspects of RBC physiology of potential physiologic benefit in SCD. Firstly, we used the rate of change in EI (a first derivative-based analysis) on the reoxygenation arm of the LORRCA trace, to identify the pO2 at which EI was observed to significantly increase from EImin, defining this as the point of unsickling (POU). Lastly, we set about quantifying the hysteresis between the O2 unloading and O2 loading EI curves, calling this the area between curves. METHODS: RBCs from SCD patients were incubated with the Hb allosteric effector 5-hydroxymethylfurfural (5HMF; 20% Hct, 37C, HMF: 0-5mM, 0-3 hrs); 5HMF binds to Hb NH2 terminal αValine1, increasing oxyHbS abundance, thereby inhibiting the mechanistic trigger for deoxygenation induced HbS polymerization.Oxygenscans were performed with elongation index (EI) determined by laser light diffraction, across the physiologic O2 gradient (pO2 ~150-10 mmHg; sample gassed with nitrogen ~1300 seconds followed by swift re-oxygenation in room air ~280 seconds). Samples were analyzed utilizing standard parameters offered by the LORRCA software in addition to our modified POS determination and analysis of POU and area between curves. RESULTS: Little change in mean POS was observed in baseline measurements (minus 5HMF) between the standard LORRCA software analysis and our modified analysis (POS pO2 = 55.1 ± 20.4 vs 56.9 ± 10.1mmHg mean±SD, respectively), however the coefficient of variance (COV) of our modified analysis was ~20% lower. The same trend was observed in samples across all doses of 5HMF. No significant difference in POS was detected with the standard analysis between any of the 5HMF doses. However, a significant reduction in POS between 0 and 5mM 5HMF final was determined with our modified analysis (POS pO2 = 56.9 ± 10.1 vs 39.8 ±11.6mmHg, respectively). A significant difference was also observed in the POU between 0 and 5mM HMF (POU pO2 = 38.3 ± 9.1 vs 21.3 ± 5.7mmHg, respectively) with HMF resulting in a lower pO2 at which unsickling was observed. This has obvious patient benefit implications, with SRBCs regaining deformability at lower pO2. Finally, a significant difference was also observed in the area between the deoxygenation and reoxygenation EI curves between 0 and 5mM HMF (area between curve = 8.9 ± 4.6 vs 4.6 ± 1.6AU, respectively). This smaller area between curves implies less change in deformability behavior between oxygenation states in the presence of 5HMF. SUMMARY: We have developed a more robust analysis methodology for the determination of POS by oxygenscan. This appears to work well even on sub-optimal scans and can detect a change in sickling characteristics for the allosteric modifier 5HMF. In addition, we suggest two further analyses parameters for oxygenscan (POU and area between curves) which reflect aspects of RBC physiology of potential physiologic benefit in SCD.

Different measurements require different benchmarks: One size does not fit all

Key Points Echocardiographic Doppler measurements do not account for the pressure recovery phenomenon and therefore estimate higher transvalvular pressure gradients (TPG) than invasive catheter‐based measurements. An observed 3‐4 mmHg mean TPG difference between self‐expanding and balloon‐expandable transcatheter valves has been observed consistently, but no clinical significance has been reported. A necessary novel classification system must provide a range of normal and abnormal values for each measurement modality and each valve type.

Discussion of Cuffless Blood Pressure Prediction Using Plethysmograph Based on a Longitudinal Experiment: Is the Individual Model Necessary?

Using the Plethysmograph (PPG) signal to estimate blood pressure (BP) is attractive given the convenience and possibility of continuous measurement. However, due to the personal differences and the insufficiency of data, the dilemma between the accuracy for a small dataset and the robustness as a general method remains. To this end, we scrutinized the whole pipeline from the feature selection to regression model construction based on a one-month experiment with 11 subjects. By constructing the explanatory features consisting of five general PPG waveform features that do not require the identification of dicrotic notch and diastolic peak and the heart rate, three regression models, which are partial least square, local weighted partial least square, and Gaussian Process model, were built to reflect the underlying assumption about the nature of the fitting problem. By comparing the regression models, it can be confirmed that an individual Gaussian Process model attains the best results with 5.1 mmHg and 4.6 mmHg mean absolute error for SBP and DBP and 6.2 mmHg and 5.4 mmHg standard deviation for SBP and DBP. Moreover, the results of the individual models are significantly better than the generalized model built with the data of all subjects.

Effect of norepinephrine challenge on cardiovascular determinants assessed using a mathematical model in septic shock: a physiological study.

The present study investigated the cardiovascular determinants of cardiac output (CO), mean systemic filling pressure analogue (Pmsa) derived by Geoffrey Parkin, efficiency of heart (Eh) and related parameters to a norepinephrine (NE) challenge [an increase of 10 mmHg mean arterial pressure (MAP) by NE] in septic shock patients using of a mathematical model. Twenty-seven septic shock patients with pulse index continuous cardiac output (PiCCO) monitoring were enrolled. These patients required NE to maintain an individualized MAP for organ perfusion after early fluid resuscitation based on their clinical condition. NE was decreased to obtain a decrease of 10 mmHg from base MAP (MAP-10mmHg), and the NE doses were adjusted to return MAP to baseline (MAPbase) and produce an increase of 10 mmHg from MAPbase (MAP+10mmHg). Two NE challenge episodes were analyzed for each patient: from MAP-10mmHg to MAPbase and from MAPbase to MAP+10mmHg. The Pmsa, pressure gradient for venous return (PGvr), and Eh (PGvr relative to Pmsa) were estimated using a mathematical model for the three MAP levels (MAP-10mmHg, MAPbase and MAP+10mmHg). A total of 54 episodes of NE challenges were obtained in 27 patients. Significant and consistent increases were observed in the central venous pressure (CVP), Pmsa, and PGvr in response during the NE titration. ΔCO negatively and significantly correlated with ΔCVP (r=-0.722, P<0.0001), ΔPmsa (r=-0.549, P<0.0001), ΔResistance of venous return (Rvr) (r=-0.597, P<0.0001), and ΔResistance of systemic vascular beds (Rsys) (r=-0.597, P<0.0001). Episodes of decreasing CO/Eh were associated with a higher ΔCVP than the CO/Eh-increasing episodes. The area under the curve (AUC) of ΔCVP to predict decreased CO by the incremental NE was 0.86, and the AUC of ΔCVP to predict decreased Eh was 0.94. A cutoff of ΔCVP >1.5 mmHg for detecting decreased CO resulted in a sensitivity of 75% and a specificity of 94.1%. A cutoff of ΔCVP >1.5 mmHg for detecting decreased Eh resulted in a sensitivity of 64.3% and a specificity of 100%. There were a highly divergent response in Eh and CO to afterload challenge episodes of an NE-induced 10mmHg increase in MAP. An increase in CVP may be an early alarm to identify the reduction in CO/Eh during an NE-induced increase of MAP.

HYPERTENSIVE PATIENTS WITH GREATER GENETIC RISK RESPOND LESS EFFECTIVELY TO TREATMENT AND ARE MORE LIKELY TO BE TREATMENT RESISTANT

Objective: Patients with resistant hypertension (RHTN) have increased cardiovascular disease risk. It is believed there may be genetic causes, although robust associations remain to be validated. Over 1,000 genetic loci have been discovered for BP from genome-wide association studies (GWAS), with application of genetic risk scores (GRS) enabling population risk stratification. However it is unknown whether genetic risk influences treatment response. We investigated whether BP associated loci: (i) are associated with RHTN; (ii) mediate the effect of antihypertensives on BP lowering response. Design and method: We analysed 6,266 patients of European ancestry with genetic data from ASCOT. BP-GRSs were constructed for systolic (SBP), diastolic BP (DBP) and pulse pressure (PP) using all available 1,167 pairwise-independent published BP-associated genetic variants, weighted by their effect estimates from our recent BP-GWAS in N∼750k individuals. We tested the BP-GRS for association with: (i) RHTN, adjusted for known non-genetic predictors: sex, age, BMI, diabetes, randomization treatment arm and left ventricular hypertrophy; (ii) BP response to monotherapy treatment, adjusted for sex, age, baseline-BP, dose and baseline antihypertensive use. All analyses adjusted for 10 principal components of ancestry. Results: Each BP-GRS is significantly associated with RHTN (P = 1.13 × 10-13, 1.96 × 10-5, 1.21 × 10-14 for SBP, DBP, PP) with increased genetic risk leading to increased odds of RHTN. Patients in the top 20% of SBP-GRS have 1.74 times greater odds of RHTN than the lowest 20% (P = 6.96 × 10-10). Additional adjustment for baseline-BP does not change conclusions. The association even remains significant (P = 5.11 × 10-4) with stronger effect (OR = 2.52) when restricted only to 1,037 patients untreated at baseline. The BP-GRS is also significantly associated with SBP and DBP response to amlodipine (N = 1,780): patients in the lowest 20% genetic risk group achieve better lowering response by 3.77mmHg mean difference between SBP pre and post treatment (P = 8.27 × 10-4). Conclusions: Our results confirm the hypothesis for a genetic contribution to RHTN, indicating RHTN patients are likely to be those with highest genetic risk of hypertension, which helps to explain the clinical challenge. We show that those with greater BP genetic risk respond less effectively to treatment and provide evidence that BP genes also influence treatment response.

Abstract P301: Evaluating the Impact of a Pharmacist-Managed Hypertension Collaborative Care Model in Vascular Neurology Patients in an Inpatient Acute Care Setting

Introduction: The utility of pharmacist-managed collaborative practice agreements (CPA) in the management of hypertension is well established in the outpatient setting. There has been little evaluation of the use of CPAs in the inpatient acute care setting, and none described specifically in the vascular neurology population. Treatment of hypertension is a critical intervention for the secondary prevention of acute ischemic stroke. This quality improvement project evaluated the implementation of a CPA for the inpatient acute care management of hypertension in vascular neurology patients at University of Virginia Health. Methods: A CPA was developed between the neurosciences clinical pharmacist group and the inpatient vascular neurology service, legally vetted, and implemented in June 2019. All vascular neurology patient charts in which an electronic CPA referral was placed from June 2019 through June 2020 were reviewed. Patients were excluded if they were discharged within 24 hours of the referral being placed. The primary objective was to describe and evaluate the implementation of a pharmacist-driven hypertension management practice in the inpatient acute care setting. All patient demographic and clinical data were analyzed using descriptive statistics. Secondary safety outcomes included documented hypotensive events (SBP &lt;90) and acute kidney injury (AKI, increase in SCr by 0.3 mg/dl within 48 hours). Results: During the study period, 26 referrals were placed, and 19 patients were included for review. On average, patients were on 2 anti-hypertensive medications prior to admission. From the time of referral to discharge (mean 6 days), systolic blood pressure (SBP) was reduced on average by 36 mmHg (mean percentage reduction 20%) and diastolic blood pressure (DBP) by 12 mmHg (mean percentage reduction 7%). Ten patients (53%) met the goal of SBP &lt; 140 at discharge. There were 5 hypotensive events and 4 instances of AKI, all of which were mild and recovered prior to discharge. Conclusion: A pharmacist-managed hypertension CPA was successfully implemented in vascular neurology patients in the inpatient acute care setting. The practice demonstrated improved blood pressure control and minimal adverse outcomes.

Transcatheter aortic valve thrombosis: Data from a French multicenter cohort analysis.

To evaluate the effectiveness of anticoagulant therapies in patients with clinical transcatheter heart valve (THV) thrombosis, to describe complications, and to assess their risk profile was the objectives. Little research has been conducted on clinical THV thrombosis. Patients with clinical THV thrombosis were identified based on greater than 50% increased transvalvular gradient on transthoracic echocardiogram confirmed by 4-dimensional computed tomography, transesophageal echocardiogram, or regression with anticoagulant therapy. A cohort free from thrombosis for more than 1,100 days postprocedure was used for comparison. Fifty-four patients with clinical THV thrombosis were identified. Most subjects (98.1%) received anticoagulant therapy which was effective (≥50% reduction in transvalvular gradient or return to postprocedure value) in 96%. The rate of serious hemodynamic or embolic complications in the thrombosis population was 31.5%. A multivariate analysis of subjects with and without thrombosis indicated a significantly increased risk of thrombosis from preexisting thrombocytopenia (odds ratio [OR] 9.96), absence of predilatation (OR=5.67), renal insufficiency (OR=4.84), and >10 mmHg mean transvalvular gradient postprocedure (OR=3.36). No recurrence of thrombosis was identified during on average 685 days follow-up. These data, from one of the largest cohorts with clinical THV thrombosis confirm anticoagulants appear effective. The rate of serious associated complications was high. The findings underline the importance of recognizing risk factors for thrombosis.

Hyperthermia, bladder pressure, and intravesical drug delivery.

469 Background: Little is known about the pharmacokinetics of intravesical chemotherapies. Various parameters can be altered including temperature, dwell time, drug concentration, and bladder pressure. Here, we hypothesize that increasing bladder pressure during instillation will improve drug delivery. Methods: An ex-vivo porcine model was developed to evaluate determinants of drug penetration into the bladder wall. Porcine bladders were suspended in isotonic saline at 37°C with a three-way Foley catheter in the bladder. Temperature probes were positioned in the extravesical bathing solution, bladder lumen, and sutured to the detrusor to ensure maintenance of desired temperatures. 2g gemcitabine in 100mL normal saline was heated to 43°C and circulated through the bladder using the Combat Bladder Recirculation System. Bladder pressures were monitored throughout each trial. After 60 minutes of dwell time, rapid dissection was performed to obtain full-thickness bladder samples from the bladder dome, posterior wall, trigone, and left and right lateral walls. Tissue was homogenized and liquid chromatography with tandem mass spectrometry (LC/MS/MS) was performed to measure gemcitabine concentration within the bladder wall. Linear regression and Pearson correlation were performed to determine the association between mean bladder pressure during instillation and drug concentration within the bladder wall. Multiple linear regression was conducted to control for bladder location and thickness. Results: Gemcitabine concentration within the bladder wall was measured 25 times across five trials. Mean gemcitabine concentration within bladder wall was 3.68 mg/g (sd 1.35). Pressure ranged from 149.8 mmHg to 277.7 mmHg (mean 194.8, sd 22.0). On univariate analysis, higher pressure was associated with increased gemcitabine concentration within the bladder wall (correlation = 0.49, p = 0.013). This result persisted after adjusting for bladder location (ß = 0.49, p = 0.006) and thickness (ß = 0.70, p = 0.03). Unstandardized regression coefficient in each of the models was 0.099 (mmHg x g)/mg, demonstrating that for each pressure increase of 10mmHg there was an associated increase in gemcitabine concentration of approximately 1 mg/g (Table). Conclusions: Data suggest that bladder pressure dramatically improves the extent of gemcitabine penetration into the bladder wall. Future research is needed to evaluate the therapeutic effect of increased gemcitabine delivery to target tissue in patients with bladder cancer. [Table: see text]