Acute Hemodynamics Research Articles

Shorter Premature Atrial Complex Coupling Interval Leads to Mechanical Dysfunction, Fibrosis, and AF in Swine.

We have previously shown that dyssynchronous premature atrial complexes (PACs) from the lateral left atrium (LA) lead to greater atrial mechanical dysfunction, remodeling, and sustained atrial fibrillation (AF) than synchronous PACs from the interatrial septum. However, the impact of PAC coupling interval (CI) on atrial remodeling is unclear. This study sought to explore the effect of PAC CI on atrial mechanics and remodeling in the swine model. A 2-phase invivo study was conducted. In the phase 1 acute study, 5 swine underwent acute invasive hemodynamics and echocardiography while delivering single-paced atrial extrastimuli with CIs varying from 450ms to 200ms. Peak LA longitudinal strain and intra-LA dyssynchrony were assessed with 2-dimensional strain echocardiography while LA and aortic pressure were directly measured. In the phase 2 chronic study, a group exposed to paced bigeminy from the lateral LA for 16weeks with a short CI of 250ms (Short-PAC, n=10) was compared with groups with PACs at a long CI of 400ms (Long-PAC, n=5) and a nonpaced control group (CTRL, n=10). Detailed electrophysiology and echocardiography studies were performed with histologic quantification of LA fibrosis at baseline and prior to sacrifice. Phase 1 revealed that as PAC CI shortened, peak LA strain decreased (P = 0.003) and LA dyssynchrony increased (P< 0.001). Phase 2 showed that after 16weeks of PACs, the Short-PAC group had greater LA dilation (terminal baseline: 5.9 ± 1.2cm2 vs Long-PAC 3.9 ± 0.5cm2 vs CTRL 0.9 ± 0.4cm2; P< 0.001) and reduced peakLAstrain during sinus rhythm (terminal baseline:-17.3 ± 3.2% vs Long-PAC-12.1 ± 2.1% vs CTRL-0.7 ± 4.2%; P<0.001). The short-PAC group had a more LA fibrosis (8.6 ± 1.0% vs Long-PAC 6.8 ± 1.0% vs CTRL 4.0 ± 1.5%; P<0.001) and higher AF inducibility (terminal baseline: 49.3 ± 13.0% vs Long-PAC 29.0 ± 6.4% vs CTRL 2.2±16.2%; P< 0.001) than the other groups. In this swine model, shorter PAC CI led to increased acute atrial mechanical dysfunction and dyssynchrony. Chronically, short-CI PACs led to greater atrial fibrosis and induced AF, suggesting that frequent, short-coupled PACs pose the highest risk for LA myopathy and AF. These insights underscore the importance of understanding the impact of PAC characteristics on atrial remodeling and arrhythmogenesis.

INVESTIGATING THE RELATIONSHIP BETWEEN BLEEDING, CLOTTING, AND COAGULOPATHY DURING AUTOMATED PARTIAL REBOA STRATEGIES IN A HIGHLY LETHAL PORCINE HEMORRHAGE MODEL.

Background: Death due to hemorrhagic shock, particularly, noncompressible truncal hemorrhage, remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently, whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer. In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared with pREBOA due to more oscillatory flow. Methods: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 min of automated pREBOA, iREBOA, or no balloon support (control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., eight key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 min). Citrated kaolin heparinase assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between the iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R time: P < 0.001; K time: P < 0.001) and clot strength (MA: P = 0.01; G: P = 0.02) over the duration of the experiment. Conclusions: Despite observing acute differences in peak proximal pressures between the iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.

IDF23-0505 Sympathetic hyperactivity in Insulin resistance and acute stress cardiovascular hemodynamics in young South Africans

IDF23-0505 Sympathetic hyperactivity in Insulin resistance and acute stress cardiovascular hemodynamics in young South Africans

Osteopontin Activation and Microcalcification in Venous Grafts Can Be Modulated by Dexamethasone.

Osteopontin has been implicated in vascular calcification formation and vein graft intimal hyperplasia, and its expression can be triggered by pro-inflammatory activation of cells. The role of osteopontin and the temporal formation of microcalcification in vein grafts is poorly understood with a lack of understanding of the interaction between haemodynamic changes and the activation of osteopontin. We used a porcine model of vein interposition grafts, and human long saphenous veins exposed to ex vivo perfusion, to study the activation of osteopontin using polymerase chain reaction, immunostaining, and 18F-sodium fluoride autoradiography. The porcine model showed that osteopontin is active in grafts within 1 week following surgery and demonstrated the presence of microcalcification. A brief pretreatment of long saphenous veins with dexamethasone can suppress osteopontin activation. Prolonged culture of veins after exposure to acute arterial haemodynamics resulted in the formation of microcalcification but this was suppressed by pretreatment with dexamethasone. 18F-sodium fluoride uptake was significantly increased as early as 1 week in both models, and the pretreatment of long saphenous veins with dexamethasone was able to abolish its uptake. Osteopontin is activated in vein grafts and is associated with microcalcification formation. A brief pretreatment of veins ex vivo with dexamethasone can suppress its activation and associated microcalcification.

Safety and efficacy of different doses of intrathecal magnesium sulfate on the acute and chronic postoperative pain in patient undergoing pelvic cancer surgeries - a randomized controlled dose finding clinical study

ABSTRACT Background and objectives Excision of tumors from pelvis causing severe pain postoperatively. Hemodynamic stability, and better analgesia were documented when MgSO4 was used as an adjuvant to local anesthesia. We aimed to investigate the effect of using intrathecal MgSO4 with different doses as an adjuvant to LAs on postoperative acute pain, hemodynamics, and chronic pain. Methods Ninety patients scheduled for pelvic surgery for excision of tumors have been included in this study and divided into three groups; all patient received general anesthesia (GA) plus intrathecal fentanyl (group A), while the second (group B) and the third (group C) received intrathecal magnesium sulfate 50 mg and 100 mg, respectively; intra- and postoperative outcomes such as hemodynamics, (LANSS) pain score, (NRS) and postoperative complications have been measured. Results The results revealed that MgSO4 in the (group B) had significant effect on decreasing the postoperative pain during the first 24 hours; the result of the three groups revealed that there was statistically significant difference between the group A and groups (B-C) (P-value >0.05), while there was insignificant statistical difference between the group B and group C. Patients in the fentanyl group requested analgesic after 6 to 8 hours (mean ±SD 8.4817 ± 0.819 mg), while patients in group B after 12 to 14 hours postoperatively (13.7450 ± 0.86477 mg) and patients in group C requested analgesia 16 hours postoperatively (13.7800 ± 1.00272 mg). LANSS score was significantly improved in groups B-C, but fewer complications such as itching, nausea and shorter time of recovery after the surgery in group B than other groups. Conclusion When comparing IT magnesium sulfate at doses of 50 and 100 to fentanyl 50 mg, we found superiority of MgSO4, in decreasing pain after surgery and ITMgSO4 50 mg achieved a reasonable balance between postoperative analgesia and side effects. In addition, ITMgSO4 has shown significant effect in decreasing the chronic pain postoperatively.

Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute haemodynamics.

Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. Right ventricular activation can be advanced through anodal capture, but there is uncertainty regarding the mechanism by which this is achieved, and it is not known whether this produces haemodynamic benefit. We recruited patients with LBBP leads in whom anodal capture eliminated the terminal R-wave in lead V1. Ventricular activation pattern, timing, and high-precision acute haemodynamic response were studied during LBBP with and without anodal capture. We recruited 21 patients with a mean age of 67 years, of whom 14 were males. We measured electrocardiogram timings and haemodynamics in all patients, and in 16, we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that RV septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration and total ventricular activation times were shorter (116 ± 12 vs. 129 ± 14 ms, P < 0.01 and 83 ± 18 vs. 90 ± 15 ms, P = 0.01). This required higher outputs (3.6 ± 1.9 vs. 0.6 ± 0.2 V, P < 0.01) but without additional haemodynamic benefit (mean difference -0.2 ± 3.8 mmHg compared with pacing without anodal capture, P = 0.2). Left bundle branch pacing with anodal capture advances RV activation by stimulating the RV septal myocardium. However, this requires higher outputs and does not improve acute haemodynamics. Aiming for anodal capture may therefore not be necessary.

Acute post-exercise internal carotid artery hemodynamics are intensity dependent in young adults

This research aimed to examine the impact of aerobic exercise intensity on acute post-exercise internal carotid artery (ICA) hemodynamics. This research tested the hypothesis that acute exercise would elicit intensity-dependent effects on ICA cross-sectional area (CSA), shear stress, and blood flow. Ten young, healthy adults (27 ± 4 years of age, 3 males, 7 females) completed a maximal oxygen uptake (VO2max) treadmill test followed by two randomized study visits that involved 30 minutes of treadmill exercise at 30% of VO2max or 70% of VO2max. At each study visit, a venous blood draw and ultrasound imaging of the ICA were completed before and 4 ± 1 min following exercise. During ultrasound imaging, beat-by-beat systemic blood pressure was measured. Vessel diameter and blood velocity were determined using automated edge detection software. ICA blood flow was calculated as: mean blood velocity x CSA x 60. Using measures of blood viscosity from the blood draw, shear stress was calculated as: (4 x viscosity x mean blood velocity)/mean vessel diameter. Mean arterial pressure and blood viscosity were not altered following exercise. ICA CSA was increased following exercise (Time: P = 0.03, Intensity: P = 0.24, Interaction: P = 0.38), but the magnitude of dilation did not differ following exercise at 30% VO2max (Δ0.01 ± 0.03 cm2) and 70% VO2max (Δ0.02 ± 0.04 cm2; P = 0.54). The impact of exercise on ICA shear stress was intensity dependent (Time: P = 0.02, Intensity: P = 0.03, Interaction: P = 0.03), such that shear stress was unaltered following exercise at 30% VO2max (Pre: 10 ± 2 dynes/cm2 vs. Post: 11 ± 3 dynes/cm2; Ppost-hoc = 0.13) but increased following exercise at 70% VO2max (Pre: 12 ± 4 dynes/cm2 vs. Post: 16 ± 4 dynes/cm2; Ppost-hoc = 0.04). ICA blood flow was increased following both exercise intensities (Time: P &lt; 0.01, Intensity: P = 0.02, Interaction: P = 0.03), but a larger increase was observed following exercise at 70% VO2max (Δ257 ± 151 mL/min) compared with 30% VO2max (Δ109 ± 129 mL/min; P = 0.03). Therefore, aerobic exercise produced intensity dependent effects on acute post-exercise ICA hemodynamics. Vigorous intensity exercise increased shear-stress and provoked a larger increase in ICA blood flow compared to light intensity exercise. However, increases in ICA CSA following exercise did not differ between the two exercise intensities. Therefore, the greater increase in ICA blood flow following vigorous intensity exercise may be related to downstream effects in addition to shear-mediated dilation of the ICA. Supported by the Wisconsin Alumni Research Foundation (JNB) and the National Institutes of Health (NS117746; JNB). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ten Years of Percutaneous Pulmonary Valve Implantation in Australia and New Zealand

This study sought to investigate the characteristics, morbidity (including the rate of infective endocarditis and valve replacement) and mortality of individuals undergoing percutaneous pulmonary valve implantation in Australia and New Zealand since the procedure has been performed. The outcomes of percutaneous pulmonary valve implantation in Australia and New Zealand have not been evaluated. Recent international data, including patients from New Zealand, suggests the rate of infective endocarditis is not insignificant. A retrospective multi-site cohort study was undertaken via medical record review at the centres where percutaneous pulmonary valve implantation has been performed. All procedures performed from 2009-March 2018 were included. Individuals were identified from local institution databases. Data was collected and analysed including demographics, details at the time of intervention, haemodynamic outcome, post procedure morbidity and mortality. Multi-site ethics approval was obtained. One hundred and seventy-nine (179) patients attended the cardiac catheter laboratory for planned percutaneous pulmonary valve implantation. Of these patients, 172 underwent successful implantation. Tetralogy of Fallot and pulmonary atresia were the most common diagnoses. The median age at procedure was 19 years (range 3-60 yrs). There was a significant improvement in the acute haemodynamics in patients undergoing percutaneous pulmonary valve implantation for stenosis. Seven (7) patients (3.9%) experienced a major procedural/early post procedure complication (death, conversion to open procedure, cardiac arrest), including two deaths. The annualised rates of infective endocarditis and valve replacement were 4.6% and 3.8% respectively. There was one death related to infective endocarditis in follow-up. Percutaneous pulmonary valve replacement is a relatively safe method of rehabilitating the right ventricular outflow tract.

Acute arterial haemodynamics activation of endothelial to mesenchymal transition in long saphenous veins. Impact on vein graft disease

Abstract Introduction The long saphenous vein (LSV) is frequently used in cardiac surgery; however, its use is complicated by late stenosis or occlusion due to the development of intimal hyperplasia (IH). TGF-β has been implicated in the process of IH however the impact of acute haemodynamic changes on the activation of TGF-β endothelial-to mesenchymal transition (EndMT) has not been assessed and it's the focus of this study. Purpose To assess the role of acute haemodynamics changes in veins implanted into arterial circulation on EndMT. Methods Surplus LSV were exposed to acute arterial haemodynamics using a perfusion bioreactor. Changes in EndMT markers at the RNA and protein level evaluated by quantitative real time PCR, RNAScope and immunofluorescence. Results The acute exposure of veins to arterial haemodynamics ex-vivo induced significant increase in inflammatory marker IL-8 expression and transcription factor TWIST1 in LSV (both p≤0.01, Figure 1A) endothelium. Furthermore, immunostaining demonstrated the activation of pSMAD (p≤0.01, Figure 1B) acutely in endothelium after 45 minutes of exposure to arterial haemodynamics. This was followed by significant increase of SMC related markers (Vimentin and α-SMA; Figure 1C, both p≤0.001) and the suppression of endothelial cell related marker CD31 after 4 hours of LSV exposure to acute arterial haemodynamics. RNAScope and IHC results showed localisation of TWIST1 RNA and protein in CD31+ (p≤0.001) and VECAD+ (p≤0.001) cells respectively following exposure to acute arterial haemodynamics (Figure 1D). Furthermore, TGF-β pathway phosphorylation array identified the activation of Smad1 (p≤0.05) but not TAK1 in LSV endothelial cells indicating that acute arterial haemodynamics activates the TGF-β–SMAD pathway specifically (Figure 1E). Conclusion The exposure of LSV to acute arterial haemodynamics is associated with the activation of TGF-β–SMAD pathway leading to EndMT changes in the endothelium of vein grafts ex-vivo. This contributes to our understanding of the changes that occur in veins after implantation into arterial circulation and that the acute changes in the endothelium and suggests that strategies to modulate TGF-β–SMAD can be utilised to modulate IH in vein grafts. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Van Geest Foundation Heart and Cardiovascular Diseases Research Fund

Role of Electromechanical Dyssynchrony Assessment During Acute Circulatory Failure and Its Relation to Ventriculo-Arterial Coupling.

IntroductionTwo parallel paradigms of cardiovascular efficiency and haemodynamic optimisation coexist in haemodynamic research. Targeting ventriculo-arterial (VA) coupling [i.e., the ratio between arterial and ventricular elastance (EV)] and electromechanical coupling are two promising approaches in acute circulatory failure. However, validation of the parameters of electromechanical coupling in critically ill patients is ongoing. Furthermore, a unifying link between VA and electromechanical coupling may exist, as EV is correlated with different times of the cardiac cycle.Materials and MethodsThis study was a retrospective analysis of a prospectively collected observational database from one tertiary center ICU. We analyzed the relationship between electromechanical dyssynchrony and acute circulatory failure hemodynamics before and after treatment (i.e., fluid expansion, dobutamine, or norepinephrine infusion). The relationship between electromechanical coupling and VA coupling was also investigated. Adult patients with haemodynamic instability were included. Haemodynamic parameters, including arterial pressure, cardiac index, VA coupling, stroke work index/pressure–volume area (SWI/PVA), t-IVT, and Tei's index, were collected before and after treatment. A t-IVT of >12 s/min was classified as intraventricular dyssynchrony.ResultsWe included 54 patients; 39 (72.2%) were classified as having intraventricular dyssynchrony at baseline. These patients with baseline dyssynchrony showed a statistically significant amelioration of t-IVT (from 18 ± 4 s to 14 ± 6 s, p = 0.001), left ventricular EV [from 1.1 (0.72–1.52) to 1.33 (0.84–1.67) mmHg mL−1, p = 0.001], VA coupling [from 2 (1.67–2.59) to 1.80 (1.40–2.21), p = 0.001], and SWI/PVA [from 0.58 (0.49–0.65) to 0.64 (0.51–0.68), p = 0.007]. Patients without baseline dyssynchrony showed no statistically significant results. The improvement in VA coupling was mediated by an amelioration of EV. All patients improved their arterial pressure and cardiac index with treatment. The haemodynamic treatment group exhibited no effect on changing t-IVT.ConclusionAcute circulatory failure is associated with electromechanical dyssynchrony. Cardiac electromechanical coupling was improved by haemodynamic treatment only if altered at baseline. The improvement of cardiac electromechanical coupling was associated with the improvement of markers of cardiocirculatory efficacy and efficiency (i.e., SWI/PVA and VA coupling). This study was the first to demonstrate a possible link between cardiac electromechanical coupling and VA coupling in patients with acute circulatory failure.

C-14 | Mechanical Thrombectomy in Intermediate-low-risk Pulmonary Embolism Patients: Acute and Long-term Outcomes from the FLASH Registry

C-14 | Mechanical Thrombectomy in Intermediate-low-risk Pulmonary Embolism Patients: Acute and Long-term Outcomes from the FLASH Registry

Effect of Levosimendan on Acute Decompensated Right Heart Failure in Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

AimsAcute decompensated right heart failure (RHF) in chronic precapillary pulmonary hypertension is often typified by a swiftly progressive syndrome involving systemic congestion. This results from the impairment of the right ventricular filling and/or a reduction in the flow output of the right ventricle, which has been linked to a dismal prognosis of short duration. Despite this, there are limited therapeutic data regarding these acute incidents. This study examined the effect of levosimendan on acute decompensated RHF in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).MethodsThis retrospective study included 87 patients with confirmed CTD-PAH complicated acute decompensated RHF between November 2015 and April 2021. We collected biological, clinical, and demographic data, as well as therapy data, from patients with acute decompensated RHF who required levosimendan treatment in the cardiac care unit (CCU) for CTD-PAH. The patients were divided into two groups according to the levosimendan treatment. Patient information between the two groups was systematically compared in hospital and at follow-up.ResultsOxygen saturation of mixed venose blood (SvO2), estimated glomerular filtration rate (eGFR), 24-h urine output, and tricuspid annular plane systolic excursion (TAPSE) were found to be considerably elevated in the levosimendan cohort compared with the control cohort. Patients in the levosimendan cohort exhibited considerably reduced levels of C-reactive protein (CRP), white blood cell (WBC), troponin I, creatinine, NT-proBNP, and RV diameter compared with those in the control cohort. A higher survival rate was observed in the levosimendan cohort.ConclusionsLevosimendan treatment could effectively improve acute decompensated RHF and systemic hemodynamics in CTD-PAH patients, with positive effects on survival in hospital and can, therefore, be considered as an alternative treatment option for improving clinical short-term outcomes.

Role of heme oxygenase in the regulation of the renal hemodynamics in a model of sex-dependent programmed hypertension by maternal diabetes.

Intrauterine programming of cardiovascular and renal function occurs in diabetes because of the adverse maternal environment. Heme oxygenase 1 (HO-1) and -2 (HO-2) exert vasodilatory and antioxidant actions, particularly in conditions of elevated HO-1 expression or deficient nitric oxide levels. We evaluated whether the activity of the heme-HO system is differentially regulated by oxidative stress in the female offspring of diabetic mothers, contributing to the improved cardiovascular function in comparison with males. Diabetes was induced in pregnant rats by a single dose of streptozotocin (STZ, 50 mg/kg ip) in late gestation. Three-month-old male offspring from diabetic mothers (MODs) exhibited higher blood pressure (BP), higher renal vascular resistance (RVR), worse endothelium-dependent response to acetylcholine (ACH), and an increased constrictor response to phenylephrine (PHE) compared with those in age-matched female offspring of diabetic mothers (FODs), which were abolished by chronic tempol (1 mM) treatment. In anesthetized animals, stannous mesoporphyrin (SnMP; 40 µmol/kg iv) administration, to inhibit HO activity, increased RVR in FODs and reduced glomerular filtration rate (GFR) in MODs, without altering these parameters in control animals. When compared with MODs, FODs showed lower nitrotirosyne levels and higher HO-1 protein expression in renal homogenates. Indeed, chronic treatment with tempol in MODs prevented elevations in nitrotyrosine levels and the acute renal hemodynamics response to SnMP. Then, maternal diabetes results in sex-specific hypertension and renal alterations associated with oxidative stress mainly in adult male offspring, which are reduced in the female offspring by elevation in HO-1 expression and lower oxidative stress levels.

An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension.

Preclinical and early clinical studies suggest that angiotensin‐converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin‐converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi‐center, open‐label, exploratory, single‐dose, dose‐escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.1, 0.2, 0.4, or 0.8 mg/kg. Dose escalation occurred after four or more participants per cohort were dosed and a review of safety, tolerability, pharmacokinetics, and hemodynamic data up to 24 h postdose was undertaken. The primary endpoint was a change in cardiopulmonary hemodynamics (pulmonary vascular resistance, cardiac index, and mean pulmonary artery pressure) from baseline. Secondary/exploratory objectives included safety and tolerability, effect on renin‐angiotensin system peptides, and pharmacokinetics. GSK2586881 demonstrated no consistent or sustained effect on acute cardiopulmonary hemodynamics in participants with PAH receiving background PAH therapy (N = 23). All doses of GSK2586881 were well tolerated. GSK2586881 was quantifiable in plasma for up to 4 h poststart of infusion in all participants and caused a consistent and sustained reduction in angiotensin II and a corresponding increase in angiotensin (1–7) and angiotensin (1–5). While there does not appear to be a consistent acute vasodilatory response to single doses of GSK2586881 in participants with PAH, the potential benefits in terms of chronic vascular remodeling remain to be determined.

Effects of Enhanced External Counterpulsation With Different Sequential Levels on Lower Extremity Hemodynamics.

Objective: This study aimed to investigate acute hemodynamics of lower extremities during enhanced external counterpulsation with a three-level sequence at the hips, thighs, and calves (EECP-3), two-level sequence at the hips and thighs (EECP-2), and single leg three-level sequence (EECP-1).Methods: Twenty healthy volunteers were recruited in this study to receive a 45-min EECP intervention. Blood flow spectrums in the anterior tibial artery, posterior tibial artery, and dorsalis pedis artery were imaged by Color Doppler ultrasound. Mean flow rate (FR), area, pulsatility index (PI), peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MV), and systolic maximum acceleration (CCAs) were sequentially measured and calculated at baseline during EECP-3, EECP-1, and EECP-2.Results: During EECP-3, PI, PSV, and MV in the anterior tibial artery were significantly higher, while EDV was markedly lower during EECP-1, EECP-2, and baseline (all P < 0.05). Additionally, ACCs were significantly elevated during EECP-3 compared with baseline. Moreover, FR in the anterior tibial artery was significantly increased during EECP-3 compared with baseline (P = 0.048). During EECP-2, PI and MV in the dorsalis pedis artery were significantly higher and lower than those at baseline, (both P < 0.05). In addition, FR was markedly reduced during EECP-2 compared with baseline (P = 0.028). During EECP-1, the area was significantly lower, while EDV was markedly higher in the posterior tibial artery than during EECP-1, EECP-2, and baseline (all P < 0.05). Meanwhile, FR of the posterior tibial artery was significantly reduced compared with baseline (P = 0.014).Conclusion: Enhanced external counterpulsation with three-level sequence (EECP-3), EECP-2, and EECP-1 induced different hemodynamic responses in the anterior tibial artery, dorsalis pedis artery, and posterior tibial artery, respectively. EECP-3 acutely improved the blood flow, blood flow velocity, and ACCs of the anterior tibial artery. In addition, EECP-1 and EECP-2 significantly increased the blood flow velocity and peripheral resistance of the inferior knee artery, whereas they markedly reduced blood flow in the posterior tibial artery.

Novel left ventricular cardiac synchronization: left ventricular septal pacing or left bundle branch pacing?

It is well recognized that a high burden of right ventricular pacing results in deleterious clinical outcomes over the long term. His bundle pacing can achieve optimal ventricular synchronization; however, relatively high pacing thresholds, low R-wave amplitudes, and the long-term performance have been concerns. Recently, left ventricular (LV) septal endocardium pacing (LVSP) has demonstrated improved acute haemodynamics. Another novel technique of intraseptal left bundle branch pacing (LBBP) via transvenous approach has been adopted rapidly and has demonstrated its feasibility and effectiveness. This article reviews the clinical application and differences between LVSP and LBBP. Compared with LVSP, LBBP has strict criteria for left conduction system capture and lead location. In addition to LV septal capture it also stimulates the proximal left bundle branch, resulting in rapid and physiological LV activation. With a uniformity and standardization of the implant procedure and definitions, it may be possible to achieve widespread application of this form of physiological pacing.

Abstract 16623: Interim Acute and 30-day Results of the Flash Registry

Introduction: FLASH, a prospective multi-center all-comers registry, is designed to evaluate real-world outcomes in pulmonary embolism (PE) patients treated with the FlowTriever System (Inari Medical, Irvine, CA). The FlowTriever System is designed to extract large PE thrombus without a need for thrombolytic drugs. Methods: FLASH will enroll up to 500 patients who will be evaluated through 6 months. The primary endpoint is a major adverse events composite of device-related death and major bleeding at 48 hours, and periprocedural device or procedure-related AEs. Secondary endpoints include changes in acute hemodynamics, utility measures, and longer-term clinical outcomes. Acute data in 203 patients and 30-day data in 170 patients has been analyzed. Results and Conclusion: This analyzed cohort included 10% high-risk and 90% intermediate-risk PE patients. The mean RV/LV ratio was 1.54±0.47, sPESI was 1.54±1.06, concomitant DVT was present in 72% and elevated biomarkers in 97% of patients. The primary endpoint occurred in 2 patients (1%) both were major bleeds (non-ICH). There were no periprocedural device related injuries or clinical deteriorations. No deaths (0% mortality) were reported at 48 hours. Significant on-table improvement in hemodynamics were seen, including an average reduction in mean PA pressure of 20% (6.1 mmHg, p&lt;0.0001) and a reduction in heart rate from a pre-procedure high of 111.9±16.9 bpm to 90.5±16.6 bpm (p&lt;0.0001). Patients with low cardiac index (&lt;2l/min/m 2 ) experienced an 18% on table improvement (0.3 l/min/m 2 , p&lt;0.0001). At 30-day follow-up, one patient had died, unrelated to the procedure (0.6% mortality) and 10 patients were readmitted (1 related, 9 unrelated to the procedure). Dyspnea significantly improved from a pre-procedure Modified Medical Research Council Dyspnea Scale average grade of 2.6±1.4 to 0.76±1.1 at 30 days, and 0.54±1 at 6 months (p&lt;0.0001). In conclusion, early results demonstrate excellent safety with immediate improvements in hemodynamics and low 30-day mortality. Data analysis is ongoing and additional results will be presented at the conference.

Abstract 12984: Long-term Prognostic Value of the Serial Change of Acute Hemodynamic Index During Hospitalization in Patients Admitted for Acute Decompensated Heart Failure

Backgrounds: Controlled heart rate (HR) and increased pulse pressure (PP) are related to better outcomes in stable heart failure. Hemodynamic response to stress evaluated by an acute hemodynamics index (AHI), the product of HR and PP, has been reported to be associated with poor outcomes in patients admitted for acute decompensated heart failure (ADHF). However, there is no information available on the long-term prognostic value of the serial change of AHI during hospitalization in patients admitted for ADHF. Methods and Results: We studied 259 patients admitted for ADHF and discharged with survival. We measured AHI (HR x PP/1000) at admission and discharge. AHI significantly decreased from admission to discharge (6.98±3.04 to 3.81±1.21 bpm·mmHg, p&lt;0.0001). During a mean follow-up period of 5.0±3.2 yrs, 53 patients had cardiac death. The change [ad-dis] of AHI from admission to discharge (AHI[ad-dis]) was significantly less in patients with than without cardiac death (1.98±2.17 vs 3.47±2.87 bpm·mmHg, p=0.0005). Multivariate Cox regression analysis revealed that AHI[ad-dis], but not PP[ad-dis], was significantly associated with cardiac death, independently of prior heart failure hospitalization, body mass index, estimated glomerular filtration rate, hemoglobin level and left ventricular end-diastolic dimension. ROC analysis revealed that AUC in AHI[ad-dis](0.668[0.588-0.749]) was greater than that in PP[ad-dis](0.637[0.572-0.717]). Patients with less AHI[ad-dis] (≤1.79 bpm·mmHg by ROC analysis) had a significantly higher risk of cardiac death than those with greater AHI[ad-dis] (adjusted hazard ratio: 3.19[1.77 to 5.76], 30% vs 13%, p&lt;0.0001). Conclusions: Cardiac death was frequently observed in ADHF patients who had less degree of the decrease in AHI during hospitalization. The change of AHI during hospitalization would be a simple and useful marker for risk stratification in patients admitted for ADHF.

The acute effect of resistance exercise on limb blood flow.

What is the central question of this study? How does resistance exercise affect peripheral haemodynamics in the active and inactive limb? What is the main finding and its importance? Preliminary data indicate that resistance exercise increases flow and shear rate in the active limb transiently. The same exercise has minimal, short-lasting influence on peripheral haemodynamics in the inactive limb, but further research is required to elaborate on resistance exercise-mediated changes in vascular function in active and inactive limbs. Current evidence indicates that to achieve maximum health benefits, regular resistance exercise should be a key component of structured physical activity. Several studies have revealed that regular resistance exercise may be associated with impaired vascular function, although this finding is inconsistent. Proposed explanations for impairment include substantial increases in blood pressure and increased retrograde blood flow in active limbs promoted by resistance exercise. However, few studies have examined the acute haemodynamics of resistance exercise in active - and even fewer in inactive - limbs. The purpose of this study was to characterise the haemodynamic responses in peripheral arteries in active and inactive limbs in response to resistance exercise using upper and lower limbs. Ten participants (five male, five female) familiar with resistance training performed three sets of 10 isotonic repetitions of right-sided bicep curls or knee extensions on separate days. Blood flow, shear rate and muscle oxygenation in the active and inactive limb, and blood pressure were measured before and for 3min after each set. Blood flow increased in response to resistance exercise in the active limb (∼8-fold and ∼6-fold for the upper and lower limb respectively), with concurrent significant increases in mean and antegrade shear rate. In the inactive limb, blood flow more than doubled for both upper and lower limb exercise, transiently, with no significant change in retrograde shear rate. These acute blood flow profiles following resistance exercise are not indicative of long-term vessel impairment based on current understanding of blood flow and shear stress patterns.

Intensive care and anesthetic management of patients with Brugada syndrome and COVID-19 infection.

Coronavirus disease 2019 (COVID‐19) spreads across the world, and the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic viral infection. Rapid diagnosis, isolation, and intensive clinical management are very important for all patients with COVID‐19, especially for those with cardiac diseases as Brugada syndrome (BrS). BrS is an arrhythmogenic disease reported to be one among the leading causes of sudden cardiac death. In these patients, episodes of lethal arrhythmias may be induced by several factors or situations, and for this reason management during ICU permanence or anesthesia must provide some precautions, avoiding factors that are known to have the potential to worsen the probability to induce arrhythmias. For ICU practitioners, management of acute respiratory failure, hemodynamics, and cardiovascular complications certainly are the key for the best treatment of these patients but to date specific data on supportive ICU care for these patients are lacking, and current recommendations are based on existing evidence from other viral infections and general intensive care management. We want to focus on some general rules, resulted from cases series and clinical practice, to be followed during the ICU management of patients with BrS and concomitant COVID‐19 infection.