Increase In Stroke Volume Research Articles

Physiological impact of oral carbohydrate preload in healthy volunteers.

Oral carbohydrate loading has become a key component of Enhanced Recovery After Major Surgery (ERAS) pathways, with potential improvements in patient comfort, nausea and vomiting, ileus and length of stay. The contribution of each component of ERAS, including carbohydrate beverages, remains unclear. We aimed to determine the impact of standardized oral carbohydrate fluid loading on haemodynamics, stroke volume and gastric state in a group of healthy volunteers. Twenty-three volunteer participants free of known cardiovascular or gastrointestinal disease, consumed 400 mL of a proprietary carbohydrate solution. Heart rate (HR), blood pressure (BP), stroke volume (SV) and gastric cross-sectional area (CSA) were measured with bedside ultrasound at baseline, 30/60/120 min post-ingestion. There were small decreases in HR, BP (<10%) that were statistically significant. There were small increases (<10%) in SV at 30 and 60 min post-ingestion, but SV had returned to baseline by 120 min. There were no changes in SV variation. Gastric CSA increased immediately post-ingestion, then decreased in a linear fashion before returning to baseline by 120 min. In a standard 400 mL dose of a carbohydrate beverage, only small increases in SV could be demonstrated in the first-hour post-ingestion. All patients had largely returned to their baseline SV and gastric CSA state within 2 h post-fluid ingestion. A mild decrease in HR and BP was noted that persisted at 120 min. A 400 mL carbohydrate beverage does not appear to have favourable cardiovascular effects in a healthy population.

Hif-1α ablation reduces the efficiency of NeuroD1 gene-based therapy and aggravates the brain damage following ischemic stroke

ABSTRACT Introduction Hypoxia-inducible factor 1α [HIF1α] regulates gene expression, allowing the organism to respond to low oxygen levels. Meanwhile, astrocytes participate in inflammatory processes and are associated with neurotoxic chemicals that can increase stroke volume, contributing considerably to the devastating effects of a stroke. Objective To evaluate whether Hif-1α ablation from the central nervous system is implicated in motor dysfunction and ischemic brain damage following stroke. Furthermore, to explore if Hif-1α ablation affects the therapeutic impact of NeuroD1 gene-based therapy. Methods Endothelin-1 [ET-1] was injected to induce ischemic stroke in mice. Both wild-type and Hypoxia-inducible factor 1α conditional knockout [Hif-1α CKO] mice were used. The effect of Hif-1α ablation was assessed by the neuron numbers, astrocyte activity, vascular endothelial growth factor [VEGF] expression, and behavioral tests. Moreover, western blot, ELISA, and RNA sequencing were used. Then, we used pAAV2/9-GfaABC1D-NeuroD1-P2A-EGFP-WPRE injection to examine the impact of NeuroD1 in Hif-1α CKO mice following ischemic stroke. Results We found that following stroke, motor dysfunction significantly increased in Hif-1α CKO mice. Furthermore, elevation of apoptosis and activation in both microglia and astrocytes were observed, consequently up-regulating neuroinflammation. Meanwhile, Hif-1α ablation significantly decreased the efficiency of NeuroD1 gene-based therapy. Conclusion Our findings demonstrate that Hif-1α ablation from the nervous system is implicated in ischemic stroke pathogenesis mainly by increasing neuron cell death and inducing astrocytes as well as decreasing the efficiency of NeuroD1. These data support the idea that manipulating HIF-1α is a viable therapeutic for ischemic stroke.

Effect of Ischemic Preconditioning on Endurance Running Performance in the Heat.

Ischemic preconditioning (IPC) is a strategy that may enhances endurance performance in thermoneutral environments. Exercising in the heat increases thermoregulatory and cardiovascular strain, decreasing endurance performance. The current study aimed to determine whether IPC administration improves endurance performance in the heat. In a randomized crossover design, 12 healthy subjects (V̇O2max: 54.4 ± 8.1 mL·kg-1·min-1) underwent either IPC administration (220 mmHg) or a sham treatment (20 mmHg), then completed a moderate-intensity 6-min running (EX1) and a high-intensity time-to-exhaustion running test (EX2) in a hot environment (35 °C, 50 % RH). Cardiac function, oxygen consumption (V̇O2), and core body temperature (TCORE) were measured. During EX2, IPC administration increased the total running time in the heat compared to the sham treatment (IPC: 416.4 ± 61.9 vs. sham 389.3 ± 40.7 s, P = 0.027). IPC administration also increased stroke volume (IPC: 150.4 ± 17.5 vs. sham: 128.2 ± 11.6 ml, P = 0.008) and cardiac output (IPC: 27.4 ± 1.7 vs. sham: 25.1 ± 2.2 ml min-1, P = 0.007) during 100% isotime of EX2. End-exercise V̇O2 (IPC: 3.72 ± 0.85 vs. sham: 3.54 ± 0.87 L·min-1, P = 0.017) and slow phase amplitude (IPC: 0.57 ± 0.17 vs. sham: 0.72 ± 0.22 L·min-1, P = 0.016) were improved. When compared with the baseline period, an increase in TCORE was less in the IPC condition during EX1 (IPC: 0.18 ± 0.06 vs. sham: 0.22 ± 0.08 °C, P = 0.005) and EX2 (IPC: 0.87 ± 0.10 vs. sham: 1.03 ± 0.10 °C, P < 0.001). IPC improves high-intensity endurance performance in the heat by 6.9 %. This performance benefit could be associated with improved cardiac and thermoregulatory function engendered by IPC administration.

Abstract 4136159: Determinants of Exercise Intolerance in Postural Orthostatic Tachycardia Syndrome: a Systematic Review

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a syndrome of an exaggerated heart rate (HR) response with standing, disproportionately affecting young women associated with exercise intolerance due to dizziness, palpitations, and/or chest pain. Research question: How does the exaggerated increase in HR with standing translate into impaired exercise tolerance in subjects with POTS? Aims: To systematically analyze determinants of exercise intolerance in subjects with POTS. Methods: We searched the National Library of Science and identifed 11 cohorts with a diagnosis of POTS and an assessment of exercise capacity. We abstracted the information including type of exercise testing, hemodynamics and gas exchange parameters (peak oxygen consumption [VO 2 ]) with exercise, and effect of interventions (if present). Results: We identified 849 subjects with POTS, female:male ratio of 8.5:1, 25±8 years, and 365 age-and sex-matched controls. A cycle ergometer was used in 8 studies (574 subjects, 68%) and a treadmill in 3 (275 subjects, 32%). Peak VO 2 was measured in 10 studies (836 subjects, 98%), and exercise hemodynamics in 9 (593 subjects, 70%). All 11 (100%) studies described a higher HR at rest and during submaximal exercise in subjects with POTS, with a similar slope of HR/load, and shorter time to peak HR. Of the 9 studies with hemodynamics, 6 (67%) reported a reduction in stroke volume (SV) with standing and with exercise, but only 1 (11%) documented a reduction in cardiac output (CO). Two studies (22%) enrolling teenagers showed a variable increase in SV and CO in POTS. Peak VO 2 was reduced in 8 (80%) studies when compared with predicted values, but only in 4 (40%) when compared with controls matched for deconditioning. Intravenous fluid administration in two studies did not affect HR, SV, CO or peak VO 2 . Exercise training in one study (19 subjects) and propranolol 20 mg in another study (11 subjects) led to improving peak VO 2 . Conclusions: An exaggerated HR response with standing and with exercise is a hallmark of POTS, a mechanism by which subjects reach a higher HR at lower workloads. While the increase in HR is associated with a reduction in SV, CO is typically maintained and occasionally increased, therefore making it an unlikely mechanism responsible for the peculiar exertional symptoms of POTS. Strategies that result in a reduction in HR may, on the other hand, translate in improved exercise capacity in subjects with POTS.

Abstract 4137186: No Room for Chronotropic Incompetence in Living Fontan Patients: Enhanced Heart Rate Increase in Response to Exercise to Compensate Low Stroke Volume Reserve

Background: Fontan patients reveal decreased peak exercise performance in combination with low peak heart rate (HR), which is frequently interpreted as chronological incompetence. This is counterproductive as HR increase has to be enhanced to compensate limited stroke volume increase in Fontan physiology. Methods: Cardiopulmonary exercise testing (CPET) data in asymptomatic Fontan patients and age-matched control subjects were retrospectively studied. Peak and submaximal CPET parameters were obtained by cycle ergometer. Chronotropic capacity was assessed by peak HR/peak [WR/kg] and submaximal slope of HR/[work rate (WR)/kg] (ΔHR/Δ[WR/kg]) for males and females, separately. Results: Table 1 presents CPET data of Fontan patients (51) and controls (65). Fontan patients showed significantly lower peak HR, peak WR, peak oxygen consumption (VO2)/kg, %predicted maximum VO2, and peak oxygen pulse (pOP)/kg than controls in both sexes whereas peak HR/peak [WR/kg] was significantly higher in Fontan patients, indicating higher HR at the maximum effort in Fontan patients than in controls. Fontan patients showed higher ΔHR/Δ[WR/kg], a marker for HR-dependency, and lower Δ[VO2/kg]/ΔHR, a surrogate of stroke volume, suggesting higher HR was compensating lower stroke volume during submaximal phase of exercise in Fontan patients. Figure 1 demonstrates a linear relationship between ΔHR/ΔWR and peak HR/peak WR in both sexes. Male Fontan patients revealed a comparable trend with controls, whereas female Fontan patients showed higher HR increase at the peak exercise effort than controls with the same ΔHR/ΔWR, suggesting more limited stroke volume reserve than male Fontan patients. Conclusions: Fontan patients showed higher HR-response to exercise than controls in both sexes due to limitation in stroke volume increase. Our data indicate that lower peak HR in Fontan patients results from early exhaustion due to limited stroke volume reserve rather than primary chronotropic incompetence.

Application of ultrasound-guided inferior vena cava collapsibility measurement in volume assessment for patients undergoing single-shot spinal anesthesia in total hip arthroplasty.

To explore the value of ultrasound in volume assessment during the perioperative period of single-shot spinal anesthesia for total hip arthroplasty. A total of 100 patients undergoing elective surgery under spinal anesthesia at our hospital from January 2022 to January 2024 were selected. Transthoracic echocardiography was used to measure the diameter of the abdominal aorta (Ao) before anesthesia (T1), 10 minutes after anesthesia (T2), and 30 minutes after anesthesia (T3). The inferior vena cava collapsibility index (IVC-CI) and the ratio of IVCe to Ao (IVCe/Ao) were calculated. A volume load test was performed 10 minutes after anesthesia. Based on the increase in stroke volume (ΔSV) after the volume load test, patients were divided into a volume-responsive group (ΔSV ≥ 15%) and a volume-nonresponsive group (ΔSV < 15%). The reliability of inferior vena cava parameters in predicting hypotension after spinal anesthesia and the value in predicting volume responsiveness postanesthesia were evaluated using ROC curves. A total of 100 patients were enrolled, 18 were withdrawn, and a total of 82 patients were included. After the volume load test, the parameters of the volume response group and the volume nonresponse group were basically consistent, and the difference was not statistically significant (P > .05). The SV of volume reaction group was significantly higher than that of volume no reaction group (P < .05). The incidence of hypotension in the volume response group was higher than that in the non-volume response group (51.28% vs 11.63%, χ2 = 15.174, P < .01). The AUC for volume reactivity prediction using IVCe, IVCi, IVC-CI, and IVCe/Ao were 0.62, 0.71, 0.70, and 0.72, respectively. IVCi, IVC-CI, and IVCe/Ao were significant predictors of volume reactivity (P < .05). The AUC predicting persistent hypotension after spinal anesthesia using IVCe, IVCi, IVC-CI, and IVCe/Ao were 0.78, 0.79, 0.70, and 0.84, respectively. IVCe, IVCi, IVC-CI, and IVCe/Ao can predict volume reactivity before anesthesia. IVCi, IVC-CI, and IVCe/Ao predicted persistent hypotension in patients with spinal anesthesia after anesthesia, and IVCe/Ao showed the best predictive effect. Thus, IVCe/Ao is a reliable parameter for predicting persistent hypotension and assessing volumetric reactivity.

Comparison of pulse pressure and stroke volume variations measured by three monitors in high-risk surgical patients

IntroductionDynamic indices of fluid responsiveness (FR) such as pulse pressure variation (PPV) and stroke volume variation (SVV) differ among hemodynamic monitors, which use proprietary algorithms, and vary even over a short period of time. We aimed to compare the baseline values, fluctuation and predictive value for FR of PPV and SVV measured by three minimally invasive monitors. Patients and methodsTwenty patients undergoing high-risk abdominal surgery were included and 45 fluid challenges were analysed. The patients were simultaneously monitored using Carescape B650, LiDCO Rapid and FloTrac/Vigileo system. Cardiac output (CO), PPV and SVV were recorded before and after the fluid challenge of 500ml of balanced crystalloid solution. An increase in CO ≥ 15 % defined fluid responders. Concurrently recorded arterial waveform was used for offline calculation of PPV. ResultsMean baseline values of the indices ranged between 8.6% and 13.4%. LiDCO showed higher fluctuation of indices compared to the other monitors. Area under the receiver operating characteristic curve (AUROC) ranged from 0.71 to 0.76 with optimal cut-off value between 7.5% and 13.9%. AUROC increased for all indices when FR was defined as an increase in stroke volume. Furthermore, a decrease in PPV or SVV after fluid challenge (ΔPPV, ΔSVV) proved a better marker of FR (AUROC 0.82 – 0.93) than baseline values with a uniform threshold of approximately -3%. ConclusionsAlthough a significant range of baselines variations and optimal cut-off values was observed, the predictive value of PPV and SVV from all the monitors was only moderate and comparable. Nevertheless, ΔPPV and ΔSVV appear to be a reliable and device-independent markers of FR.

Predictors and clinical impact of worsening left ventricular ejection fraction after mitral transcatheter edge-to-edge repair.

Little is known about the effects of left ventricular ejection fraction (LVEF) worsening after transcatheter edge-to-edge valve repair (TEER) for mitral regurgitation (MR). This study investigated the predictors and clinical impact of LVEF worsening after TEER for primary MR (PMR) and secondary MR (SMR). This study included 2,019 patients (493 with PMR and 1,526 with SMR) undergoing successful TEER (postprocedural MR grade ≤2+) in the OCEAN-Mitral registry. The patients were categorised into worsened LVEF (wEF), defined as a relative decrease of >12.9% in LVEF at discharge, and preserved LVEF (pEF). The serial changes in left ventricular (LV) function at 1 year were also evaluated. Following TEER, 657 (32%) patients demonstrated wEF. The pEF group demonstrated both decreased left ventricular end-diastolic volumes (LVEDV) and end-systolic volumes (LVESV), and the wEF group showed significantly increased LVESV at discharge. Higher LVEF, larger LVEDV, higher B-type natriuretic peptide levels, and moderate/severe aortic regurgitation predicted wEF. Compared with baseline, the wEF group still demonstrated lower LVEF (46% to 43%; p<0.001) but significantly increased stroke volume (48 mL to 53 mL; p=0.001) at 1 year. The incidence of death or heart failure hospitalisation was similar between the wEF and pEF groups (hazard ratio 1.14, 95% confidence interval: 0.72-1.80; p=0.84) and also in patients with PMR and SMR. LVEF worsening after TEER was not uncommon and was caused by the increased LVESV. LV volumes and some patient-specific factors predicted worsened LVEF which was not associated with long-term clinical outcomes. OCEAN-Mitral registry: UMIN-CTR ID: UMIN000023653.

Evidence that mitral and/or tricuspid regurgitation diminishes stroke volume increase during exercise

Abstract Background and Purpose The severity of heart failure can be evaluated by peak oxygen consumption (VO2). Cardiac output is one of the major essential factors to determine the VO2. Therefore, cardiac output increases linearly as the exercise intensity increases. However, in mitral regurgitation, effective stroke volume decreases due to some blood flowing back into the left atrium from the left ventricle. This reduction may compromise oxygen delivery to working muscles and diminish oxygen uptake. Peak VO2/HR is known to indicate the stroke volume at the peak exercise, but since c(A-V)O2 difference shows almost a similar change pattern during a ramp protocol, VO2/HR during the load is also reported to be an indicator of stroke volume (SV) at that work rate. However, there are no investigations that have examined the extent to which the increase in cardiac output during stress is affected by the severity of mitral regurgitation. Therefore, we investigated the influence of the degree of regurgitant volume in mitral regurgitation (MR) and tricuspid regurgitation (TR) affects the SV increasing response to exercise load. Additionally, we examined whether blunted SV increase influences on the peak VO2. Methods Among 525 patients who underwent cardiopulmonary exercise test (CPX) at our institution from January 2023 to October 2023, 518 patients (143 females, 375 males, mean age 65.2±15.0 years old) where precise analyses of CPX was possible. CPX was performed using breath-by-breath gas analysis, and an incremental load test (10watts/min) was administered until exhaustion. The rate of increase in VO2/HR per watt during an incremental loading (Δ(VO2/HR)/ΔWR) was used as an indicator of the degree of increase in SV. Typically, SV increases up to 60% of maximum load, around AT, after which it stops increasing and plateaus. Therefore, the slope of Δ(VO2/HR)/ΔWR was examined from the initiation of ramp loading to AT. The degree of reflux was evaluated by echocardiography and classified as none/trivial, mild and moderate/severe. The number of people in each group of None/trivial, mild, moderate/severe was, 392, 83, 30 for MR, and 416, 64, 24 for TR. Δ(VO2/HR)/ΔWR was evaluated for each degree of reflux, using ANOVA to determine whether there was a difference between groups. Results As shown in the Figure1, Δ(VO2/HR)/ΔWR decreased as the reflux flow rate increased for both MR and TR. Concurrently, peak VO2 also decreased in the moderate/severe group compared to the non/trivial-reflux group for both MR and TR (MR: 17.5±5.4 mL/min/kg vs. 14.9±3.5 mL/min/kg, TR: 17.2±5.3 mL/min/kg vs. 13.6±3.8 mL/min/kg). Conclusion The Δ(VO2/HR)/ΔWR obtained through CPX has been shown to be an index that can evaluate the severity of reflux. Additionally, it was also demonstrated that as regurgitation flow increased, true stroke volume decreases, which is correlated with a reduction in peak VO2.

Diagnostic value of low dose dobutamine stress echocardiography in paradoxical low flow low gradient aortic stenosis

Abstract Background In aortic stenosis with low-gradient scenarios distinguishing between fixed and pseudo-severe stenosis becomes challenging. Low-dose dobutamine stress echocardiography (DSE) is recommended for classical low-flow low- gradient stenosis with reduced ejection fraction. Doubts of DSE's utility in paradoxical low-flow low-gradient (PLFLG) stenosis when ejection fraction is preserved are partially reasoned by proposed inefficiency in generating a contractile reserve 1. Guidelines advocate an integrated approach, combining various clinical and imaging aspects 2. Purpose This study aimed to investigate usefulness of DSE in PLFLG stenosis, identifying specific features to predict the possibility of generating significant stroke volume augmentation and distinguishing fixed aortic stenosis. Methods We identified patients with aortic stenosis who underwent DSE and multi-modality imaging at our centre between 2020 and 2023. Among them, those with PLFLG situations were used for detailed analysis. Multiple linear regression analysis was performed to identify parameters predictive of significant contractile reserve, defined as 20% stroke volume increase from baseline. For patients demonstrating contractile reserve we assessed predefined parameters by receiver operating characteristics (ROC) analysis to predict fixed stenosis defined as final aortic valve area &amp;lt; 1cm² and valve area change &amp;lt;0.2cm² or final mean pressure gradient &amp;gt;40mmHg. For predictive value of Agatston score we conducted post-hoc analysis. Results Among 256 DSE cases, 67 were conducted for PLFLG stenosis. Patients were 82 years of median age and mostly female (63%). Symptoms included dyspnea in 90% and angina in 40% of cases. Baseline echo showed median aortic valve area (indexed to body surface area) of 0.8cm² (0.44cm²/m²) with mean pressure gradient of 20mmHg. Contractile reserve was inducible in 70% of patients, of which 74% showed criteria of fixed stenosis. Higher left ventricular end-diastolic diameter (LVESD) and lower baseline systolic flow-rate were predictive for contractile reserve (p&amp;lt;0.05). Among patients with contractile reserve ROC for baseline mean pressure gradient, acceleration time (median 0.08s; range 0.04-0.11s) and acceleration time to ejection time index (0.28; range: 0.148-0.458) revealed good prediction of fixed stenosis in DSE meanwhile Agatston calcium score (median 1076; range: 301-8821) did not (figure 1). No correlation was found between Agatston score probability of severe stenosis and aortic valve pressure gradient behavior with increased stroke volume (figure 2). Conclusion DSE proves to be a useful a method in the differentiation between fixed and pseudo-severe stenosis in PLFLG situation. Our findings question the predictive value of Agatston score for aortic valve behavior with increase of stroke volume and warrant further investigations regarding value of acceleration time and acceleration time to ejection time index in those patients.Receiver operating characteristicsPost-hoc analysis of Agatston score

Acute changes in right ventricular geometry and function following transcatheter tricuspid valve interventions

Abstract Background Little is known about acute changes in right ventricular (RV) function and geometry following transcatheter tricuspid edge-to-edge repair (T-TEER) or transcatheter tricuspid valve replacement (TTVR). Pressure-strain-volume loop-derived myocardial work metrics showed associations with myocardial energetics and contractility in conditions accompanied by volume overload, suggesting their potential utility in patients with tricuspid regurgitation (TR). Purpose To define acute changes in RV volumes and RV myocardial work following T-TEER and TTVR using conventional and pressure-strain-volume derived RV work metrics. Methods In this multicenter, observational study, 3D echocardiographic datasets and invasively acquired RV pressures were collected before and after transcatheter tricuspid valve procedure. Using dedicated software (ReVISION, Argus Cognitive) 3D RV volumes and strains were quantified and decomposed to longitudinal, radial and anterio-posterior motion. Forward stroke volume (SV) was calculated by subtracting TR volumes from RV 3D end-diastolic volume (EDV) and end-systolic volume (ESV) difference. Three-dimensional pressure-strain-volume loops were constructed and global RV work-index (RV-Wi) was calculated. Changes in RV parameters before and after the intervention were compared using paired-samples t test. Results Of 37 patients included in this study (65% male), 20 underwent T-TEER and 17 underwent TTVR. Compared to T-TEER patients, patients undergoing TTVR had higher prevalence of torrential TR at baseline but also achieved a higher reduction in TR volumes after the intervention (44 ± 11 ml vs 60 ± 16ml; p = 0,001). Following T-TEER there was a significant reduction in RV EDV (240 ± 93 ml vs 200 ± 80 ml; p &amp;lt; 0.001) and increase in SV (55 ± 34 ml vs 68 ± 26 ml; p = 0.036). Following TTVR there was a significant increase in RV ESV (121 ± 46 vs 146 ± 48, p = 0.003) and no significant change in SV (47 ± 24 ml vs 55 ± 20 ml; p = 0.143). There was significant reduction in RV strain and ejection fraction (EF) (all p &amp;lt; 0.001) primarily driven by reduction of radial motion component in both groups. RV-Wi increased in 35% (7/20) of T-TEER patients and in 18% of (3/17) TTVR patients. Conclusion An acute reduction in RV EF was observed in all patients and was mainly caused by decrease in RV EDV in T-TEER patients and increase in RV ESV in TTVR patients. Despite decrease of conventional metrics of RV function in both groups, an increase in RV-Wi was observed in 27% of all patients.Baseline and follow-up characteristicsCentral Figure

Speckle tracking of left ventricle in pediatric patients with hemodynamically significant patent ductus arteriosus (PDA): case–control study

BackgroundLeft ventricle (LV) volume overload is observed with hemodynamically significant PDA as it causes left to right shunting, leading to increased pulmonary blood flow. This overload causes LV remodeling as LV increases stroke volume in trial for compensation, but in larger shunts, patients may develop symptoms of congestive heart failure. Two-dimensional (2D) speckle-tracking echocardiography has emerged as a technique for objective and quantitative evaluation of global and regional myocardial function, independent of the angle of myocardial insonation.Aim of the workThis study aimed to evaluate left ventricular function by 2-dimensional speckle tracking in children with hemodynamically significant PDA.MethodsThis prospective controlled study was performed on 54 children divided into two groups (34 as cases and 20 as controls) to compare echocardiographic measurements. Conventional Echocardiography, tissue Doppler, and Speckle tracking were done for all patients, and measurements were compared.ResultsThere was a statistically significant difference (p value < 0.001) in global longitudinal strain (GLS) in the PDA group indicating a decrease in LV function in PDA patients. This difference was observed in several conventional echocardiographic parameters but not in tissue Doppler in our study.ConclusionLeft ventricle global strain is an important predictor of the myocardial performance index of the Left ventricle in patients with hemodynamically significant PDA and outweighs other conventional echocardiographic parameters and tissue Doppler indices.

Impact of systemic lupus erythematosus on cardiovascular morphologic and functional phenotypes: a Mendelian randomization analysis.

Previous studies have established a correlation between systemic lupus erythematosus (SLE) and cardiovascular health, but the potential causal effects of SLE on heart function and structure remain poorly understood. Cardiovascular magnetic resonance imaging (CMR), a novel non-invasive technique, provides a unique assessment of cardiovascular structure and function, making it an essential tool for evaluating the risk of heart disease. In this study, we performed a Mendelian randomization analysis to determine the causal relationship between SLE and CMR traits. Genetic variants independently linked to SLE were selected from a genome-wide association study (GWAS) containing 5,201 cases and 9,066 controls as instrumental variables. A set of 82 CMR traits was obtained from a recent GWAS, serving as preclinical indicators and providing preliminary insights into the morphology and function of the four cardiac chambers and two aortic segments. Primary analysis employed a two-sample Mendelian randomization study using the inverse-variance weighted method. Heterogeneity testing, sensitivity analyses, and instrumental variable strength assessments confirmed the robustness of the findings. SLE exhibited a correlation with increased stroke volume (βLVSV = 0.007, P = 0.045), regional peak circumferential strain (βEcc_AHA_9 = 0.013, P = 0.002; βEcc_AHA_12 = 0.009, P = 0.043; βEcc_AHA_14 = 0.013, P = 0.006), and global peak circumferential strain of the LV (βEcc_global = 0.010, P = 0.022), as well as decreased regional radial strain (βErr_AHA_11 = -0.010, P = 0.017). This research presents evidence of a potential causal association between traits of SLE and alterations in cardiac function, guiding cardiac examinations and disease prevention in lupus patients.

Airborne polystyrene nanoplastics exposure leads to heart failure via ECM-receptor interaction and PI3K/AKT/BCL-2 pathways

Environmental contamination has been recognized as a significant threat to human well-being, and recent findings of microplastic presence in human cardiac tissues have raised concerns. However, research on the effects of airborne nanoplastics (NPs) on cardiac physiology remains limited. We utilized a comprehensive body exposure apparatus to simulate the impact of airborne polystyrene NPs pollution, focusing on understanding how airborne NPs affect cardiac morphology and function. Following two weeks of NPs exposure, mice exhibited a 23.89 ± 8.30 % reduction in heart mass, a 20.05 ± 2.97 % decrease in heart rate as detected, and a myocardial electrical conduction block. Echocardiography showed significant changes in cardiac contractility, with increases in cardiac ejection fraction and stroke volume of 13.00 ± 3.00 % and 43.00 ± 17.00 %, respectively. In addition, histologic assessments revealed signs of ventricular hypertrophy, ventricular myocardial hypertrophy, and myocardial necrotic fibrosis. Of particular interest, our mechanistic investigations highlighted the harmful effects of NPs on cardiac structure and function, mediated through extracellular matrix (ECM) receptor interactions and the PI3K/AKT/BCL-2 signaling pathway. The insights gained provide a foundation for understanding the risks posed by airborne NPs to human cardiac health, emphasizing the need for increased vigilance and implementation of mitigation strategies in environmental management.

Central Hemodynamic and Thermoregulatory Responses to Food Intake as Potential Biomarkers for Eating Detection: Systematic Review.

Diet-related diseases, such as type 2 diabetes, require strict dietary management to slow down disease progression and call for innovative management strategies. Conventional diet monitoring places a significant memory burden on patients, who may not accurately remember details of their meals and thus frequently falls short in preventing disease progression. Recent advances in sensor and computational technologies have sparked interest in developing eating detection platforms. This review investigates central hemodynamic and thermoregulatory responses as potential biomarkers for eating detection. We searched peer-reviewed literature indexed in PubMed, Web of Science, and Scopus on June 20, 2022, with no date limits. We also conducted manual searches in the same databases until April 21, 2024. We included English-language papers demonstrating the impact of eating on central hemodynamics and thermoregulation in healthy individuals. To evaluate the overall study quality and assess the risk of bias, we designed a customized tool inspired by the Cochrane assessment framework. This tool has 4 categories: high, medium, low, and very low. A total of 2 independent reviewers conducted title and abstract screening, full-text review, and study quality and risk of bias analysis. In instances of disagreement between the 2 reviewers, a third reviewer served as an adjudicator. Our search retrieved 11,450 studies, and 25 met our inclusion criteria. Among the 25 included studies, 32% (8/25) were classified as high quality, 52% (13/25) as medium quality, and 16% (4/25) as low quality. Furthermore, we found no evidence of publication bias in any of the included studies. A consistent postprandial increase in heart rate, cardiac output, and stroke volume was observed in at least 95% (heart rate: 19/19, cardiac output: 18/19, stroke volume: 11/11) of the studies that investigated these variables' responses to eating. Specifically, cardiac output increased by 9%-100%, stroke volume by 18%-41%, and heart rate by 6%-21% across these studies. These changes were statistically significant (P<.05). In contrast, the 8 studies that investigated postprandial thermoregulatory effects displayed grossly inconsistent results, showing wide variations in response with no clear patterns of change, indicating a high degree of variability among these studies. Our findings demonstrate that central hemodynamic responses, particularly heart rate, hold promise for wearable-based eating detection, as cardiac output and stroke volume cannot be measured by any currently available noninvasive medical or consumer-grade wearables. PROSPERO CRD42022360600; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=360600.

Effects of integrative therapy with Du Meridian moxibustion, ear acupuncture, and alprazolam on cardiac function and neurotransmitter levels in patients with coronary heart disease and insomnia: An observational study.

To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy.

Randomized Crossover Trial of 2-Week Ketone Ester Treatment in Patients With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2D). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2D with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2D and HFpEF remain unknown. A total of 24 patients with T2D and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period. During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P<0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (P<0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs. In patients with T2D and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2D and HFpEF. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.

A Novel Model of Venovenous Extracorporeal Membrane Oxygenation in Rats with Femoral Cannulation and Insights into Hemodynamic Changes.

The application of venovenous (VV) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance for the treatment of acute severe respiratory failure. Since no rat model of VV ECMO therapy with femoral drainage has yet been described, although this cannulation strategy is commonly used in humans, this study aimed to establish such a model. Twenty male Lewis rats were randomly assigned to receive a sham procedure or VV ECMO therapy. After the inhalative induction of anesthesia, animals were intubated and the vascular accesses were placed surgically. While venous drainage was achieved through a modified multi-orifice 18 G cannula that was placed in the inferior vena cava through the femoral vein over a guide wire with an ultra-flexible tip, the venous return was realized via a shortened 20 G cannula into the jugular vein. Hemodynamic data were obtained from a tail artery and left ventricular pressure-volume catheter. Repetitive blood gas analyses were carried out, and systemic inflammation was measured using an enzyme-linked immunosorbent assay. While animals in the ECMO group showed adequate oxygenation and decarboxylation, there was no evidence of recirculation. VV ECMO therapy increased stroke volume (SV), cardiac output (CO), and left ventricular end-diastolic volume (LVEDV). ECMO-induced inflammation was reflected in increased levels of tumor necrosis factor alpha. However, no differences in interleukins 6 and 10 were seen. This study describes a frequently used cannulation strategy in humans for a rat model of VV ECMO. Despite successful oxygenation and decarboxylation, the oxygenated blood may reduce pulmonary vascular resistance and lead to an increased LVEDV, which is associated with increased SV and CO. This model allows us to answer research questions about topics such as intestinal microcirculation in further studies.

Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study.

Heart failure mortality remains high despite recent progress in pharmacological treatment. AZD3427 is a selective long-acting analog of relaxin, a vasodilatory hormone with antifibrotic effects. We assessed the safety, pharmacokinetics, and pharmacodynamics of AZD3427 in healthy volunteers and patients with heart failure on standard-of-care therapy. In this first-in-human, phase 1a/b, randomized, single-blind, placebo-controlled study, healthy volunteers were randomized 6:2 to receive a single dose of AZD3427 or placebo by subcutaneous injection in 5 mixed-ethnicity cohorts (5, 10, 30, 90, or 270 mg) and 1 Japanese-descent cohort (270 mg), or by intravenous injection in 1 cohort (15 mg). After confirming safety and tolerability in healthy volunteers, 3 cohorts of patients with heart failure and left ventricular ejection fraction ≤40% and 3 cohorts with ejection fraction ≥41% were randomized 6:2 to receive 5 weekly doses of AZD3427 (5, 15, or 45 mg) or placebo by subcutaneous injection. In total, 56 healthy volunteers and 48 patients with heart failure were randomized. AZD3427 was well tolerated at all doses. After subcutaneous administration, AZD3427 was absorbed slowly, and exposure was approximately linear across the dose range. In patients with heart failure, AZD3427 terminal half-life was 13 to 14 days and there were numerical increases in stroke volume and estimated glomerular filtration rate. No treatment-emergent antidrug antibodies were detected. AZD3427 had favorable safety and pharmacokinetic profiles. Hemodynamic changes in patients with heart failure were consistent with the anticipated effects of a relaxin analog. These findings support further development of AZD3427 as a novel long-term treatment for patients with heart failure. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04630067.

Left Ventricular Unloading Using Intra-aortic Entrainment Pumping Before Reperfusion Reduces Post-AMI Infarct Size

BackgroundAnterior myocardial infarction standard of care prioritizes swift coronary reperfusion. Recent studies show left ventricular (LV) unloading with transvalvular axial flow pumps for 30 minutes before reperfusion (vs immediate reperfusion) decreases 28-day infarct size. Intra-aortic entrainment pumping, using hardware located away from the heart to provide support throughout the cardiac cycle, decreases effective systemic vascular resistance and augments visceral blood flow and pressure, and may reproduce this benefit with a decreased risk. This study characterized the hemodynamic effects of unloading before and during reperfusion using intra-aortic entrainment pumping and investigated whether unloading decreased anterior myocardial infarction scar size. Methods and ResultsYorkshire swine were subjected to 90 minutes of left anterior descending artery balloon occlusion and randomly assigned to immediate reperfusion (n = 6) vs 30 minutes unloading before reperfusion followed by 120 minutes of further unloading (n = 7). Unloading was achieved using percutaneous entrainment pumping in the descending aorta. The anterior myocardial infarction model matches that used in recent transvalvular pumping studies. Mortality before randomization was 22%. After randomization, mortality was 36% for immediate reperfusion and 0% for unloading. Unloading showed immediate hemodynamic benefit that increased through reperfusion and continued support, leading to distinct differences in cardiac function between groups after 30 minutes of reperfusion. Unloading increased stroke volume and cardiac efficiency at this timepoint relative to preocclusion baseline and reduced 28-day LV scar size by 37%–45%. ConclusionsWe present the first preclinical data showing extracardiac LV unloading before coronary reperfusion using intra-aortic entrainment pumping decreases 28-day infarct size. Extracardiac unloading to decrease LV scar size may provide an alternative to transvalvular pumping with potential advantages, including reduced risk.