Hemodynamic Response Research Articles

A Prospective Randomised Comparative Study of Baska Mask and I-Gel for Airway Management in Elective Surgeries: Focus on Airway Sealing Pressure, Insertion Time, and Haemodynamic Response

Introduction: General anesthetic procedure requires a safe and open airway. Endotracheal intubation is the gold standard for airway management; it is being replaced by supraglottic airway devices because they are easy to introduce, better tolerated and results in a lesser haemodynamic response. As both the Baska mask and I-gel have a non-inflatable self-sealing mechanism, these two devices were compared in our study in terms of time taken for insertion, airway sealing pressure, the number of attempts, hemodynamic changes, and complications. Methods: A Prospective comparative study was conducted on 90 patients (45 in each group), aged 18-60 years, undergoing elective surgeries under general anesthesia at Tertiary care Hospital, Madurai. Patients were randomized into two groups using the computer generated statistical software STATA version14 (Texas, USA): Group B: Airway was secured by insertion of Baska mask. Group I: Airway was secured by insertion of I Gel. Following assessments were done to evaluate the SAD: Time taken to insert the device, airway sealing pressure, rate of successful insertion, number of attempts, Haemodynamic parameters, laryngopharyngeal morbidity. Data were analyzed using Student t-tests and chi-square tests, with p < 0.05 considered significant. Results: The mean airway sealing pressure of the Baska mask (26.1+6.1 cmH2O) was significantly higher than that of the I-gel (23.1± 5.9 cmH2O) with a P value of 0.019 which was statistically significant. In our study the time taken to insert the device, for Baska mask it was 18.9+4.1 seconds and for the I gel it was 17.2±5.1 seconds with a P value of 0.089 which was statistically insignificant. In our study there was no statistical difference between Baska mask and I-gel groups in regards to hemodynamic changes (Heart rate and Mean arterial pressure). This may be due to the same stress response produced by the both devices. Conclusion: Baska mask is superior to I-gel in positive pressure ventilation under general anaesthesia for short surgical procedures with statistically significant higher airway sealing pressure though it has comparable time of insertion, haemodynamic changes and laryngopharyngeal morbidity.

Impact of intracranial hypertension and cerebral perfusion pressure on spreading depolarization.

Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO2), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.

Applications of Near Infrared Spectroscopy and Mirror Therapy for Upper Limb Rehabilitation in Post-Stroke Patients: A Brain Plasticity Pilot Study

Objectives: The aim of this study was to identify the neural pattern activation during mirror therapy (MT) and explore any cortical reorganization and reducing asymmetry of hemispheric activity for upper limb rehabilitation in post-stroke patients. Methods: A box containing a mirror was placed between the arms of the patients to create the illusion of normal motion in the affected limb by reflecting the image of the unaffected limb in motion. We measured the cerebral hemodynamic response using near-infrared spectroscopy (NIRS). We enrolled ten right-handed stroke patients. They observed healthy hand movements in the mirror (MT condition) while performing various tasks (MT condition), and then repeated the same tasks with the mirror covered (N-MT condition). Results: Significant activation of some brain areas was observed in the right and left hemiparesis groups for the MT condition, while lower levels of activation were observed for the N-MT condition. The results showed significant differences in hemodynamic response based on oxygenated (HbO) concentrations between MT and N-MT conditions across all tasks in sensorimotor areas. These neural circuits were activated despite the motor areas being affected by the brain injury, indicating that the reflection of movement in the mirror helped to activate them. Conclusions: These results suggest that MT promotes cortical activations of sensory motor areas in affected and non-affected brain sides in subacute post-stroke patients, and it encourages the use of these tools in clinical practice.

Pain-Discriminating Information Decoded From Spatiotemporal Patterns of Hemodynamic Responses Measured by fMRI in the Human Brain.

Functional magnetic resonance imaging (fMRI) has been widely used in studying the neural mechanisms of pain in the human brain, primarily focusing on where in the brain pain-elicited neural activities occur (i.e., the spatial distribution of pain-related brain activities). However, the temporal dynamics of pain-elicited hemodynamic responses (HDRs) measured by fMRI may also contain information specific to pain processing but have been largely neglected. Using high temporal resolution fMRI (TR = 0.8 s) data acquired from 62 healthy participants, in the present study we aimed to test whether pain-distinguishing information could be decoded from the spatial pattern of the temporal dynamics (i.e., the spatiotemporal pattern) of HDRs elicited by painful stimuli. Specifically, the peak latency and the response duration were used to characterize the temporal dynamics of HDRs to painful laser stimuli and non-painful electric stimuli, and then were compared between the two conditions (i.e., pain and no-pain) using a voxel-wise univariate analysis and a multivariate pattern analysis. Furthermore, we also tested whether the two temporal characteristics of pain-elicited HDRs and their spatial patterns were associated with pain-related behaviors. We found that the spatial patterns of HDR peak latency and response duration could successfully discriminate pain from no-pain. Interestingly, we also observed that the Pain Vigilance and Awareness Questionnaire (PVAQ) scores were correlated with the average response duration in bilateral insula and secondary somatosensory cortex (S2) and could also be predicted from the across-voxel spatial patterns of response durations in the middle cingulate cortex and middle frontal gyrus only during painful condition but not during non-painful condition. These findings indicate that the spatiotemporal pattern of pain-elicited HDRs may contain pain-specific information and highlight the importance of studying the neural mechanisms of pain by taking advantage of the high sensitivity of fMRI to both spatial and temporal information of brain responses.

Melatonin versus gabapentin as premedication for anxiolysis and attenuation of hemodynamic response to laryngoscopy and intubation in general anesthesia

Melatonin versus gabapentin as premedication for anxiolysis and attenuation of hemodynamic response to laryngoscopy and intubation in general anesthesia

Comparison of hemodynamic responses to orotracheal intubation with Tuoren video laryngoscope and Macintosh direct laryngoscope in adult hypertensive patients

Comparison of hemodynamic responses to orotracheal intubation with Tuoren video laryngoscope and Macintosh direct laryngoscope in adult hypertensive patients

Commentary: Effects of occlusion pressure on hemodynamic responses recorded by near-infrared spectroscopy across two visits

Commentary: Effects of occlusion pressure on hemodynamic responses recorded by near-infrared spectroscopy across two visits

Acute Effect of Intradialytic Aerobic Exercise on Hemodynamic Response, Dialysis-Related Side Effects and Proteome in Patients with Kidney Failure: A Pilot Study

Acute Effect of Intradialytic Aerobic Exercise on Hemodynamic Response, Dialysis-Related Side Effects and Proteome in Patients with Kidney Failure: A Pilot Study

A Comparative Study of Magnesium Sulfate, Lignocaine, and Propofol for Attenuating Hemodynamic Response During Functional Endoscopic Sinus Surgery Under General Anaesthesia: A Prospective Randomized Trial.

This study functional endoscopic sinus surgery (FESS) is a surgical procedure requiring minimal bleeding to optimize the surgical field. This study aimed to evaluate the effectiveness of magnesium sulfate, lignocaine, and propofol in attenuating hemodynamic response. The primary objective of this study was to compare the efficacy of these agents in reducing hemodynamic response. The secondary objectives included assessing the quality of the surgical field, recovery time, and total neuromuscular dose. We randomly allocated 105 patients scheduled for FESS into three groups: lignocaine, propofol, and magnesium sulfate. Heart rate and mean arterial pressure were recorded every 5 min for the first 30 min, followed by measurements every 10 min at the end of the procedure. Moreover, recovery time, total neuromuscular blocking dose, and surgical field score were noted upon completion of the procedure. Statistical analysis was conducted using the number cruncher statistical systems version 9.0.8 software. All three groups showed comparable hemodynamic response and surgical field scores. The recovery time was notably longer in the magnesium sulfate group [10.94 min (2.45)] than in the lignocaine [4.37 min (1.03)] [95% confidence interval (CI) -7.32, -5.83; P=0.000] and propofol groups [4.60 min (0.60)] (95% CI 5.60, 7.095; P=0.000). Moreover, the total neuromuscular blocking agent used was significantly lower in the magnesium sulfate group [5.89 mg (0.47)] than in the lignocaine [6.26 mg (0.56)] (95% CI 0.66, 0.03; P=0.035). Propofol, magnesium sulfate, and lignocaine exerted equal efficacy in attenuating hemodynamic responses during surgery and ensuring a satisfactory surgical field. However, magnesium sulfate led to significantly longer recovery times compared with propofol and lignocaine. In addition, magnesium sulfate required a significantly lower total dose of neuromuscular blocking agents than lignocaine.

Low Caloric Intake Confers Cardiovascular Protection and Improves Functional Capacity Without Affecting Immunological Response in Sedentary Older Adults

Background: Aging is characterized by a decline in the cardiovascular hemodynamic response, which may be aggravated by undernutrition. However, no study has evaluated whether low caloric intake may affect cardiovascular hemodynamics and its possible relation with functional capacity and immune response in older adults. Methods: Sixty-one older adults of both genders were enrolled in this study and were classified as normocaloric (n = 18) and hypocaloric (n = 43). All volunteers were evaluated for cardiovascular hemodynamics using impedance cardiography (PhysioFlow®); functional capacity by the 1′ sit-to-stand test with SpO2 monitoring; whole-blood analysis using an automated hematocytometer (Sysmex®); and levels of IL-6, TNF-alpha, IL-10, and Klotho by ELISA. Results: The hypocaloric group presented impaired functional capacity, measured by a reduced number of sit-to-stand repetitions (p < 0.0251) and impaired delta of SpO2 (p < 0.0307). In contrast, the hypocaloric group presented an improved stroke volume (p < 0.0352), systemic vascular resistance (p < 0.0075), and systemic vascular resistance index (p < 0.0184). In addition, no changes were observed in the whole-blood analysis (p > 0.05) or for IL-6 (p > 0.05), TNF-alpha (p < 0.05), IL-10 (p < 0.05), and Klotho (p > 0.05). Conclusions: A long-term hypocaloric diet in eutrophic older adults’ resulted in an enhanced cardiovascular hemodynamic response but was associated with reduced functional capacity without changes in the immune response.

Sustained paradoxical vasodilation and blood pressure lowering in response to sympathetic stimulation as markers of disease severity and poor survival in primary AL amyloidosis.

Abstract Background AL patients present sustained paradoxical vasodilation in response to sympathetic stimulation by cold pressor test (CPT). The clinical relevance of this finding is unknown. Purpose We investigated the association between CPT-induced vascular and hemodynamic responses with clinical characteristics of the disease in AL amyloidosis. Methods We consecutively recruited 113 newly diagnosed patients with AL amyloidosis before treatment initiation. High resolution ultrasonography was used to measure the maximum vasodilation of the brachial artery in response to a cold stimulus and 3 minutes after its withdrawal. Systolic (SBP) and diastolic blood pressure (DBP) were measured at the same timepoints. Clinical and laboratory makers of autonomic dysfunction were also measured in a subgroup of the population. All-cause and cardiovascular (CV) mortality were defined as end-points of the study. Results Sustained vasodilation post CPT (%pCPT) was associated with markers of autonomic dysfunction, namely dipping status (p<0.05) and sudomotor dysfunction (p=0.064) and with NYHA stage, baseline NTproBNP and heart failure (p<0.05 for all). DBP%pCPT was associated with the neuropathy symptom scale (NSS Autonomous, p=0.032), while SBP%pCPT was inversely associated with Mayo stage. Vasodilation%pCPT was independently associated with CV death (adjusted HR=1.154, p=0.017) while both DBP%pCPT (HR=0.955, p=0.027) and SBP%pCPT (HR=0.947, p=0.04) were independently associated with all cause death (adjusted for the core model including age, sex, SBP, Mayo stage and nerve involvement). Overall survival was worse in AL patients who demonstrated a decrease in SBP%pCPT than in those who exhibited an increase or kept it stable (log rank test, p=0.024). The same applies to DBP%pCPT(log rank test, p=0.002). Regarding CV death, Vasodilation%pCPT above 5.86% was associated with increased risk of CV death (log rank test, p=0.002). Conclusions In AL amyloidosis, sustained paradoxical vasodilation and decreased SBP and DBP in response to sympathetic stimulation were associated with autonomic dysfunction, more severe cardiac involvement and poor survival.

Invasive hemodynamic response to exercise in hemodynamically significant aortic stenosis with preserved left ventricular ejection fraction

Abstract Background Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. Purpose To describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%, and to identify the variables associated with the steepness of the pulmonary capillary wedge pressure (PCWP)/cardiac output (CO) slope defined as (peak exercise PCWP-rest PCWP)/(peak exercise CO-rest CO). Methods Patients with aortic valve area (AVA) ≤1.5 cm² underwent right heart catheterization at rest and during maximal exercise measuring pulmonary artery pressures, PCWP, CO and PCWP/CO slope. Patients were stratified in three groups: 1) discordant LG AS (AVA ≤1.0 cm² and mean gradient <40 mmHg); 2) moderate AS (AVA >1.0 cm²) and 3) high-gradient severe AS (AVA ≤1.0 cm² and mean gradient ≥40 mmHg). Results Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) high-gradient severe AS. The PCWP/CO slope was significantly steeper in discordant LG: median 3.3 mmHg/L/min (interquartile range: 2.2 mmHg/L/min) and high-gradient severe AS: 2.7 mmHg/L/min (1.5 mmHg/L/min) compared to moderate AS: 1.9 mmHg/L/min (2.0 mmHg/L/min), p=0.004. In a linear regression model adjusted for age, sex and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO slope. Furthermore, patients with discordant LG AS had a leftward and upward shift in the PCWP/CO slope. Conclusions Discordant LG and high-gradient severe AS had similar hemodynamic response to exercise with steeper PCWP/CO slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left-upward shift in PCWP/CO slope for discordant LG compared to high-gradient severe AS indicates that, this group also has latent heart failure with preserved ejection fraction physiology.

Effects of Intraoperative Lignocaine Infusion on Heamodynamics and Postoperative Analgesic Requirement after Day Case Laparoscopic Surgery

Background:Intravenous lignocaine is an amide local anaesthetic known for its analgesic, anti-hyperalgesic, anti-inflammatory and anti-arrhythmic properties. During perioperative period of laparoscopic surgeries haemodynamic alteration occurs due to laryngoscopy, intubation, and surgical excision, gas insufflation during pneumoperitoneum, inadequate analgesia and inadequate depth of anaesthesia. Intravenous lignocaine is often administered to suppress the haemodynamic response and as an analgesic agent. We aimed to evaluate the effect of intravenous infusion of lignocaine on haemodynamic response and post-operative analgesic requirement. Objectives:The purpose of this study was to evaluate the effect of intravenous infusion of lignocaine on haemodynamic and postoperative analgesic requirements after laparoscopic day case surgeries. Material and method:Four hundred Sixty (460) patients were selected who’s were going to be operated for laparoscopic surgeries (Laparoscopic Cholecystectomy, laparoscopic Hernioplasty, laparoscopic appendicectomy, Diagnostic laparoscopy due to infertility) were grouped into exposed (Group L) who were received lignocaine infusion @1mg/kg/hr and controlled (Group C) who were received placebo. Systematic random sampling was employed. Results:Demographic characteristics were comparable between the groups p>0.05. In lignocaine group intraoperative mean systolic blood pressure, mean diastolic blood pressure, mean arterial blood pressure and mean heart rate were significantly lower than control group (p<0.05). Twenty four hour mean VAS score (0 – 10 cm) at immediate recovery, 1st, 2nd, 3rd, 6th, 12th and 24th hour were lower in lignocaine group (p<0.05). The mean time of first analgesic requirement were longer (120 minutes) in lignocaine group compared to 40 minutes in control group (p<0.001) and the mean total tramadol consumption is less in lignocaine group (p<0.001). Conclusion:Intra operative lignocaine infusion causes more haemodynamic stability and decreases postoperative pain score, required longer time for first analgesic requirement and reduced total analgesic consumption in laparoscopic surgeries. J Bangladesh Coll Phys Surg 2024; 42: 312-320

Mechanical right ventricular involvement is independent of right coronary arterial bed and has a prognostic impact in acute myocardial infarction complicated by cardiogenic shock

Abstract Background In Acute Myocardial Infarction complicated by Cardiogenic Shock(AMI-CS), understanding the implications of right ventricular involvement (RVi) is crucial for refining risk stratification and optimizing management. Purpose Distinguish the prognosis in RVi at baseline(RVB) and persistent(RVP) in AMI-CS Methods 357 patients with AMI-CS+PAC serial measures at 0, 6, 12, 24h. RVi was defined as the presence of all 4 criteria PAPI<1; RVSWi≤4.08; RAP≥15 mmHg; and PVC/PCP≥0.86 and persistent as the presence of the 4 criteria at 4 time points. For hemodynamic measures, repeated measures ANOVA; and KM curves and Cox regression were performed. Results 300 without vs 57 with RVB. Additionally, 344 without vs 13 had RVP. Killip-Kimball classification showed a higher significant association with both RVB(P=0.042). A higher percentage of RVB received vasopressin(P=0.008), and there was a significant association with levosimendan use(P=0.009) in RVP. The higher MODS score, RVB(P=0.017) and RVP(P=0.029). The number of vasoactives was higher in RVB(P=0.031) RVP(P=0.009). Finally, the phenotypic characterization revealed a significant association with RVB(P=0.001) and RVP(P=0.032) more cardio-metabolic. The SCAI-CSWG classification indicated a higher proportion in the E category for both RVB(P=0.046) and not significant in RVP(P=0.405). Overall, mortality rates did not differ significantly between in RVB(P=0.174) or RVP(P=0.117), although there was a trend towards higher mortality in patients with RVi. Age, sex, DM, HTN, previous MI, PCI, CABG, stroke, and type of MI, primary reperfusion, LVEF, and laboratory parameters did not differ. RVB had higher heart rate(P=0.036), RAP, PASP(both P<0.001), lower SBP(P=0.049), cardiac output(P=0.004), index(P=0.001), power(P=0.012), power index(P=0.002), CPI(RAP), perfusion pressure, PAPi(both P<0.001), Stroke volume(SV, P=0.001), SVi(P<0.001), LVSWi(P=0.001), and RVSWi(P<0.001). RVP higher RAP(<0.001), and lower cardiac output(P=0.008), index(P=0.005), power(P=0.034), power index(P=0.029), CPI(RAP)(P=0.002), perfusion pressure(P=0.035), PAPi(P<0.001), SV(P=0.018), SVi(P=0.011), LVSWi(P=0.034) RVSWi(P<0.001). Importantly interaction between group*time was found in RVB in RAP(P<0.001), mPAP(P=0.038), perfusion pressure(P=0.002) and RVSWi(P<0.001) and in RVP in SV(P=0.014), SVi(P=0.013) and LVSWi(P=0.028) suggest that RVi had different hemodynamic response. For RVB a reduction of -4.16 days in survival time (-7.79, -0.54, P=0.024); Logrank P=0.035. Similarly, for RVP demonstrated a significant reduction of -7.27 days (-14.08, -0.47, P=0.036); Logrank P=0.017. No significant of the culprit artery in RVB, RVP (P>0.05) was observed. RVB and RVP was strongly associated with a higher prevalence of RVi (STe-V3/4R) on ECG (35.1 vs. 11.7%, and 61.5 vs. 13.7%, P<0.001). Conclusion In AMI-CS, RVi, whether baseline or persistent, is associated with distinct hemodynamic profiles and a trend toward higher mortality.Figure 1.Hemodynamics of RVB(A-C) & RVP(D-F)Figure 2.Survival of RVB, RVP (A, B) & HR(C)

Assessment of circulating biomarkers and hemodynamic response during stress to detect early cardiopulmonary complications in systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is characterised by persistent immune-inflammatory system activation and excessive extracellular matrix (ECM) accumulation leading to fibrosis. Exercise Doppler Echocardiography (EDE) is a promising method to detect the early changes of fibrosis-related pulmonary and myocardial complications, like elevated left ventricular filling pressure or stress-induced pulmonary hypertension (PH). Aims The study aims to assess the linkage between the activity of fibrosis markers and abnormal exercise haemodynamics during stress in patients with SSc. Methods A total of 18 patients with SSc were enrolled in the single-centre prospective study (age 54±15,5years, 94,4 % women). SSc patients with resting PH and moderate to severe pulmonary fibrosis were excluded. According to a standardised protocol, all subjects underwent resting and exercise echocardiography on a semi-recumbent cycle ergometer with an incremental (25 watts) workload up to the maximally tolerated workload. Measurements focused on the left ventricular diastolic function (E/e’) and right ventricular haemodynamics (estimated systolic pulmonary pressure: PASP, right ventricular coupling: TAPSE/PASP, pulmonary vascular resistance: PVR). Blood samples were taken immediately before the stress test, and the Matrix Metalloproteinase-9 and 2 (MMP-9, MMP-2) levels were assessed with gelatin zymography method. Results During the EDE, PASP from baseline increased significantly (24,6mmHg±11 vs 38±16mmHg, p <0,0001), also PVR (1,2±0,49 vs 1,5±0,15 Wood unit, p<0,001) RV coupling was decreased significantly (1,2±0,68 vs 0,93±0,5, p<0,001). Left ventricular E/e’ was also increased during the stress (8,2±2 vs 10,5±5,1, p<0,05). Enzymatically active MMP-9 level was significantly correlated with RV coupling at rest and stress (p<0,05, r 0,63 at rest and r 0,52 at stress) and negatively correlated with PASP (p<0,05, r:-0,62 at rest and r -0,5 at stress). MMP-2 level only negatively correlated with resting PASP (p<0,05, r:-0,527). The left ventricular parameters did not show any relationship with MMP levels. Conclusions The level of circulating MMP-9 predicts haemodynamic behaviour during stress in SSc. MMPs could be a promising marker for detecting early changes in the right ventricle-pulmonary circulation unit.

Beat-to-beat analysis of hemodynamic response to mental and psychological stress in sickle cell anemia

Abstract Vaso-occlusive crises are a hallmark symptom of sickle cell disease. Physical stressors can trigger decreased microvascular blood flow and increase the risk for vaso-occlusive crises. However, the effect of mental and psychological stressors on vascular physiology in sickle cell disease is not well-established. We hereby examined fluctuations in continuous blood pressure to evaluate hemodynamic changes in sickle cell disease patients during mental and psychological stress. Thirteen sickle cell disease subjects from the Children’s Hospital Los Angeles and 11 healthy volunteers were recruited. Continuous blood pressure was recorded during two mental tasks and one psychological stress task. Systolic beat-to-beat blood pressure variability measurements were calculated for each subject. Three very short-term blood pressure variability metrics served as outcome measures: standard deviation, coefficient of variation, and average real variability. Peripheral augmentation index was calculated from arterial waveforms. Linear mixed effects models evaluated associations between patient factors and outcome measures. Sickle cell disease patients exhibit increased systolic blood pressure variability in response to psychological stress. All subjects exhibited a decrease in systolic blood pressure variability in response to mental stress tasks. During mental stress, both groups displayed increased augmentation index, reflective of stress-induced vasoconstriction, while psychological stress in sickle cell disease patients led to both decreased mean arterial pressure and increased augementation index, suggestive of uncompensated vasoconstriction. These findings emphasize the impact of mental and psychological stressors on vascular function in sickle cell disease and the potential for monitoring physiological signals to predict vaso-occlusive crisis events.

Worse arterial pressure reservoir capacity is associated with exacerbated hemodynamic response to capnogram changes and more labile intraoperative cardiopulmonary-metabolic coupling

Abstract Background The apparent promise of capnography as a cardiac monitor based on the coupled cardiopulmonary response to metabolic changes remains hampered by inconsistent results in studies investigating previous correlations between hemodynamics (e.g.cardiac output) and end-tidal CO2 (EtCO2).(1,2,3) Excess pressure (Pexcess), a dynamic sub-component of pressure waveform representing pressure beyond buffering capacity (reservoir pressure) of elastic large arteries, strongly correlates with aortic flow in humans, suggesting the Pexcess as a promising tool for non-invasive hemodynamic monitoring.(4,5) Purpose We aimed to clarify potential cofounders and pathophysiological mechanisms modifying the EtCO2-arterial hemodynamic coupling, by analysing the intra-operative temporal relations of paired reservoir-excess and capnogram parameters Methods In 190 patients with normal pre-operative pulmonary function tests who underwent non-cardiac surgery, simultaneous capnogram and intra-arterial pressure signals were analysed off-line. Signal windows (>2 minutes) of maximum and minimum mean arterial pressure were autoidentified, the capnogram and pressure signals were averaged into a single representative cycle, to extract reservoir-excess pressure and capnogram parameters (EtCO2, expiratory slope, alpha slope, and plateau slope) accordingly.(6,7) Arterial reservoir capacity (ARC) was defined as Preservoir/Pexcess, which was used to stratify patients into quartiles. Relationships between maximum changes in capnogram and pressure parameters were analysed (Figure 1). Results The ΔEtCO2 and ΔPa mean were correlated significantly in all groups. In patients with the highest ARC (Q4), Pexcess remained unaltered in response to ΔEtCO2 (r:0.095 p:0.545), unlike other subgroups with significant positive correlations. In Q4 (the highest ARC group), the increment in Preservoir was the main cause of ΔPa in relation to ΔEtCO2. In contrast, the ΔEtCO2 - ∆Pexcess relationship was most pronounced in the group with the poorest ARC (r:0.634 p:0.005), underlying the significance of the pressure reservoir behaviour as a determinant of metabolic oscillations in arterial hemodynamics, even though the changes in ΔEtCO2 were equivalent.(Figure 2) Conclusion(s) Worse arterial pressure reserve capacity is associated with an exacerbated hemodynamic response to capnogram changes and a more labile cardiopulmonary-metabolic coupling, characterised by a pronounced increase in excess pressure in response to increased EtCO2 in patients with low ARC. Substantial Pa alterations accompanying EtCO2 changes had opposite drivers in low and high ARC groups (predominant augmentation of Preservoir vs Pexcess). Utilisation of the capnogram for cardiac hemodynamic monitoring is substantially affected by ARC, hence it should be considered while developing capnogram-based monitoring indices.Figure 1.Methodology and example casesFigure 2.Main results

Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH) study

Abstract Introduction Pulmonary arterial hypertension (PAH) is characterised by pre-capillary pulmonary vascular remodelling. Imatinib, a tyrosine kinase inhibitor, was the first treatment investigated in PAH patients with the primary aim of targeting vascular remodelling. A Phase 3 study showed that imatinib 400mg daily reduces pulmonary vascular resistance and increases exercise capacity but only 43% of patients continued the drug for 6 months. Concerns about safety prevented regulatory approval. Purpose To identify a safe and tolerated dose of oral Imatinib and evaluate efficacy in the dose range 100-400mg daily. Methods Oral Imatinib was added to the background therapy of 17 patients with PAH; prior intracranial haemorrhage was excluded by cross sectional imaging and none were receiving an anticoagulant. The first patient started on 100mg daily. The next 12 patients were recruited serially at a minimum of 4 week intervals and started on 200mg, 300mg or 400mg, according to a Bayesian adaptive design (Continuous Reassessment Method, CRM). Patients 14-17 were recruited as an extension cohort to better understand the safety and tolerability of the 100mg and 200mg doses. The primary endpoint was safety and tolerability at 4 weeks. Imatinib was continued for up to 24 weeks. Thirteen patients had implanted devices that provided remote daily measurements of cardiopulmonary haemodynamics and heart rate and rhythm and physical activity. Non-invasive measures of systemic blood pressure, weight and oxygen saturations were made remotely. We compared the time-haemodynamic response relationship with that produced by licensed treatments in a similar patient cohort. Results The recommended starting dose from the CRM was 200mg daily. The most common side effect was nausea. Imatinib reduced mean pulmonary artery pressure (P<0.01), increased cardiac output (P=0.08) and reduced total pulmonary resistance (TPR, P<0.001, Figure). There was a clear dose-TPR response relationship (r2=0.52, p<0.01). A reduction in TPR was evident within the first week and plateaued at 4-5 weeks. Withdrawal of Imatinib led to an increase to baseline in TPR over 4-5 weeks. This contrasts with a sharp fall in TPR with licensed therapy and rapid increase on treatment withdrawal. There was a small reduction in systemic vascular resistance (P<0.05) with Imatinib that reached plateau before TPR. Conclusions Oral Imatinib 200mg daily is well tolerated and effective as an add-on treatment in PAH. The time course of the initial haemodynamic response and the gradual return to baseline on withdrawal distinguishes Imatinib from licensed treatments and is supportive of a mechanism of action beyond reliance on vasodilation. Remote monitoring enables the safe evaluation of the withdrawal of an investigational drug in patients established on best medical therapy.Figure 1.

Is unsatisfactory outcome of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy predictable?

Abstract Background Alcohol septal ablation (ASA) has been introduced for left ventricular outflow tract gradient (LVOTG) reduction in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, some patients may not profit from ASA. Thus, we identified characteristics of patients with unsatisfactory outcome of ASA in a large single-center cohort. Methods Consecutive ASAs between 1997 and 2023, performed at our institution, were retrospectively enrolled. Those ASAs performed in patients with missing follow-up (FU), previous septal reduction therapy (SRT), and atypical HOCM were excluded. Patients with unsatisfactory outcome (PUO) were defined as continuing to meet the guideline criteria for SRT (NYHA ≥III or NYHA ≥II with exertional syncope and resting/exercise-induced LVOTG ≥50mmHg). PUO were compared to patients with good outcome (PGO). Results are expressed in % or median and interquartile range (IQR). Pre-procedural predictors of poor hemodynamic outcome were identified using logistic regression analysis. Results 65 of 1003 patients were PUO (6.5%). Those were younger (48.0 years [40.5-61.8] vs. 57.0 years [IQR 47.0-67.0] in PGO; p=0.0030), more often reported syncope at baseline (35.4% vs. 22.2% in PGO; p=0.0214), and had lower body-mass-index (26.4kg/m2 [23.8-29.2] vs. 27.7kg/m2 [25.2-23.1] in PGO; p=0.0160). In PUO, resting LVOTG was higher at baseline (53.0mmHg [24.5-82.0]) than in PGO (40.0mmHg [22.0-75.0]; p=0.0292; Table 1). Differences in sex, family history of sudden cardiac death, dyspnoea, medication, and interventricular septum diameter (IVSD) were not observed at baseline (all p>0.05; Table 1). Age (OR 1.023; CI: 1.005-1.042; p=0.0129), syncope at baseline (OR 1.890; CI: 1.049-3.324; p=0.0296), and BMI (OR 1.072; CI: 1.007-1.145; p=0.0355) were found to independently influence poor hemodynamic response to ASA using multiple logistic regression controlling for confounders. However, sex, baseline IVSD, and LVOTG were not found to influence poor hemodynamic outcome (p>0.05). There were no differences with regard to the number of embolized branches (1 in both groups), the size of the balloon used to cover the septal branch (1.5mm in both groups), the volume of ethanol (PUO: 1.4ml [1.0-2.0]; PGO: 1.5ml [1.2-2.0]), or creatine kinase release (PUO: 879.0U/l [375.0-1187.0]; PGO: 842.0U/l [501.5 - 1234]) (all p>0.05). At 6-months-FU, PUO had significantly higher IVSD (18.0mm [13.5-22.0] vs. 16.0mm [12.0-19.0] in PGO; p=0.008), higher resting LVOTG (31.0mmHg [20.0-55.5] vs. 14.0mmHg [10.0-22.0] in PGO; p<0.0001) and higher exercise-induced LVOTG (105.0mmHg [84.5-143.0] vs. 35.0mmHg [22.0-64.0] in PGO; p<0.0001). Conclusion ASA was overall effective with only few patients experiencing unsatisfactory outcome. Syncope, age, and BMI were found predicting poor hemodynamic outcome.Baseline characteristics

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: mitral fibrin study

Abstract Background/Introduction The management of heart failure (HF), particularly in the context of reduced ejection fraction, is further complicated by an increased risk of thromboembolic events. Structural alterations of both left ventricle and mitral valve contribute to mitral regurgitation (MR). However, the body of evidence provides inconclusive insights into the relationship between MR and thromboembolic risk. Purpose This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on thrombin generation, clot permeation and clot lysis time in HF patients with severe MR eligible for mitral TEER. Methods A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points. Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed. Comprehensive evaluations also covered echocardiographic, laboratory, and clinical parameters. Results TEER induced changes in fibrinogen levels (p=0.009, visit 3 vs. visit 2) and improved fibrin clot properties over a 50-day follow-up (Ks, p=0.005, visit 3 vs. visit 2). No significant differences were observed among time points in analyzed blood clot parameters. Linear regression, incorporating thrombin generation variables, Ks, and CLT for delta NT-proBNP, highlighted CLT as the sole predictor of NT-proBNP change between visit 2 and visit 1 (p=0.03; R2=0.18). Conclusions MR reduction through TEER led to transient alterations in fibrinogen concentration and improved fibrin clot characteristics. Additionally, baseline CLT emerged as a significant predictor of early NT-proBNP reduction, emphasizing its role as a key indicator of the hemodynamic response to TEER.