Increase In Stroke Volume Research Articles

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 < 1cm² and valve area change <0.2cm² or final mean pressure gradient >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<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 < 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 < 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.

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.

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 (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown. A total of 24 patients with T2DM 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 T2DM 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 T2DM 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.

Evaluation of fluid responsiveness using liver compression in dogs with experimentally induced hypovolemia.

To investigate whether liver compression (LC) could increase stroke volume (SV) by more than 15% in healthy, anesthetized dogs with hypovolemia and suggest LC as a novel method to evaluate fluid responsiveness. 6 healthy Beagles. This prospective, nonrandomized experimental study was conducted from November 2023 to February 2024. The dogs were anesthetized with isoflurane and mechanically ventilated under neuromuscular blockade. After instrumentation, the dogs underwent the following 4 experimental stages in a sequential, nonrandomized manner: stage 1, baseline; stage 2, 30% withdrawal of circulating blood volume; stage 3, 50% infusion of the collected blood; and stage 4, the remaining 50% infusion of the collected blood. At each stage, SV via pulmonary artery thermodilution and hemodynamic variables were measured before, during, and after the LC. In stage 2, LC significantly increased mean SV by 30%, from 6.9 to 9 mL/beat. Simultaneously, LC significantly increased mean arterial pressure by 11 mm Hg and mean central venous pressure by 2 mm Hg, while pulse pressure variation significantly decreased from 28% to 22%. In stages 1, 3, and 4, LC did not significantly change mean SV, mean arterial pressure, and pulse pressure variation; however, mean central venous pressure significantly increased during stage 3. This study demonstrates that LC at 22 mm Hg for 1 minute could increase SV more than 15% in anesthetized, hypovolemic dogs and LC could be used as a novel method to evaluate fluid responsiveness.

A comparative study examining the impact of coronary artery bypass grafting surgery with non-extracorporeal circulation on heart function and structure in patients with various forms of coronary heart diseases.

The aim of this study is to assess alterations in heart function and structure in patients diagnosed with non-ST segment elevation acute myocardial infarction (NSTEAMI), unstable angina (UA), and stable angina (SA) 1 year after undergoing off-pump coronary artery bypass grafting (OPCABG) performed without extracorporeal circulation. A total of 182 patients who underwent OPCABG were included and classified into 3 groups based on their preoperative diagnosis: the NSTEAMI group (n = 68), the UA group (n = 64), and the SA group (n = 50). Cardiac ultrasonography data were collected for all groups both preoperatively and 1 year postoperatively. Clinical data were subjected to statistical analysis. In the NSTEAMI group, postoperative observations revealed increases in left ventricular stroke volume and left ventricular end-systolic diameter, along with reductions in left ventricular end-diastolic volume (LVEDV) and left ventricular end-diastolic diameter (LVEDD) 1-year post-surgery. The UA group demonstrated decreases in LVEDV and LVEDD 1-year post-surgery. Similarly, the SA group exhibited an increase in left ventricular ejection fraction (LVEF) and reductions in LVEDV and LVEDD 1-year post-surgery. Comparative analysis of cardiac ultrasonography data revealed that the NSTEAMI group displayed significantly lower left ventricular stroke volume and notably higher left ventricular end-systolic diameter and volume compared to the UA and SA groups 1-year post-surgery. Furthermore, the SA group exhibited significantly elevated LVEF compared to the UA and NSTEAMI groups 1-year post-surgery. Cardiac ultrasonography findings indicate that all 3 groups exhibited improvements in cardiac function and left ventricular structure 1-year post-surgery. However, the NSTEAMI group demonstrated more substantial improvements in comparison to the UA and SA groups.

New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Veno-Arterial Extracorporeal Membrane Oxygenation in the Rat.

Despite significant efforts toward improving therapy for septic shock, mortality remains high. Applying veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) in this context remains controversial. Since the cannulation of the femoral artery for V-A ECMO return leads to lower body hyperoxia, this study investigated the impact of V-A ECMO therapy on the intestinal and hepatic microcirculation during septic shock in a rodent model. Thirty male Lewis rats were randomly assigned to receive V-A ECMO therapy with low (60 mL/kg/min) or high (90 mL/kg/min) blood flow or a sham procedure. Hemodynamic data were collected through a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by intravenous administration of lipopolysaccharide (1 mg/kg). The rats received lung-protective ventilation during V-A ECMO therapy. The hepatic and intestinal microcirculation was measured by micro-lightguide spectrophotometry after median laparotomy for two hours. Systemic and pulmonary inflammation was detected via enzyme-linked immunosorbent assays (ELISA) of the plasma and bronchoalveolar lavage (BAL), respectively, measuring tumor necrosis factor-alpha (TNF-α), interleukins 6 (IL-6) and 10 (IL-10), and C-X-C motif ligands 2 (CXCL2) and 5 (CXCL5). Oxygen saturation and relative hemoglobin concentration were reduced in the hepatic and intestinal microcirculation during V-A ECMO therapy, independent of the blood flow rate. Further, rats treated with V-A ECMO therapy also presented elevated systolic, diastolic, and mean arterial blood pressure and increased stroke volume, cardiac output, and left ventricular end-diastolic volume. However, left ventricular end-diastolic pressure was only elevated during high-flow V-A ECMO therapy. Blood gas analysis revealed a dilutional anemia during V-A ECMO therapy. ELISA analysis showed an elevated plasma CXCL2 concentration only during high-flow V-A ECMO therapy and elevated BAL CXCL2 and CXCL5 concentrations only during low-flow V-A ECMO therapy. Rats undergoing V-A ECMO therapy exhibited impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Increased pulmonary inflammation was detected only during low-flow V-A ECMO therapy in septic shock.

Dobutamine Stress Echocardiography in Low-Gradient Aortic Stenosis

Guidelines recommend the use of dobutamine stress echocardiography (DSE) in patients with low-gradient aortic stenosis (AS) and left ventricular ejection fraction (LVEF)<50%. However, a paucity of DSE data exists when LVEF >35%. To examine the diagnostic accuracy of DSE in patients with low-gradient AS with a wide range of LVEF and to examine the interaction between the diagnostic accuracy of DSE and LVEF. Patients with mean gradient <40mm Hg, aortic valve area <1.0cm2, and stroke volume index ≤35mL/m2 undergoing DSE and cardiac computer tomography (C-CT) were identified from 3 prospectively collected patient cohorts and stratified according to LVEF: LVEF<35%, LVEF 35% to 50%, and LVEF>50%. Dobutamine stress echocardiography and C-CT were performed on patients with low-gradient AS. Severe AS was defined as aortic valve calcification score ≥2,000 arbitrary units (AU) among men and ≥1,200 AU for women on C-CT. Of 221 patients included in the study, 78 (35%) presented with LVEF <35%, 67 (30%) with LVEF 35% to 50%, and 76 (34%) with LVEF >50%. Mean-gradient and aortic valve peak velocity during DSE showed significant diagnostic heterogeneity between LVEF groups, being most precise when LVEF <35% (both areas under the curve [AUC]=0.90), albeit with optimal thresholds of 30mm Hg and 377cm/sec and a limited diagnostic yield in patients with LVEF ≥35% (AUC=0.67 and 0.66 in LVEF 35% to 50% and AUC=0.65 and 0.60 in LVEF ≥50%). Using guideline thresholds led to a sensitivity/specificity of 49%/84% for all patients with LVEF <50%. While DSE is safe and leads to an increase in stroke volume in patients with low-gradient AS regardless of LVEF, the association between DSE gradients and AS severity assessed by C-CT demonstrates important heterogeneity depending on LVEF, with the highest accuracy in patients with LVEF <35%.

Tricuspid Regurgitation Stratification Predicts the Time Course of Systemic Right Ventricle Dysfunction Among Patients on ACE-I/ARB

BackgroundProgressive systemic right ventricle (sRV) dysfunction is a significant challenge in adult congenital heart disease. Current guidelines do not specify effective heart failure medications for patients with sRV; however, previous studies have relied on semiquantitative assessments. The advancement of cardiac magnetic resonance (CMR) imaging as the gold-standard modality offers quantitatively accurate assessments even for complex cardiac anomalies. Therefore, we aimed to investigate prognostic factors associated with sRV dysfunction in patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE-I/ARB), using CMR-derived quantitative values. MethodsWe conducted a retrospective cohort study of 17 adult patients with sRV treated with ACE-I/ARB and performed logistic regression analysis, with the primary outcome defined as sRV ejection fraction (sRVEF) deterioration. ResultsOver an average follow-up period of 68.7 months, sRVEF deterioration occurred in 3 patients (17%). Logistic regression analysis identified tricuspid regurgitation (TR) as a potential independent prognostic factor for the primary outcome (odds ratio = 1.11; 95% confidence interval, 1.00-1.31). Furthermore, patients with mild TR (TR fraction ≤15%; N = 12) experienced improvements in sRVEF between the initial and last CMR assessments (from 49.1% ± 8.4% to 56.7% ± 8.0%, P = 0.0029), with increased stroke volume from 68.2 ± 18.6 to 79.5 ± 17.2 mL (P = 0.0029). In contrast, these changes were not observed in patients with moderate or severe TR (TR fraction >16%) (N = 5). ConclusionsOur CMR-based evaluation highlights the potential utility of TR stratification in predicting the changes in sRVEF among patients with sRV on ACE-I/ARB. Future randomized controlled trials that consider TR severity are required to elucidate the significance of ACE-I/ARB therapy.

Evaluation of fetal cardiac morphology and function by fetal heart quantification technique in the normal second and third trimesters.

The study of fetal heart is receiving increasing attention. Fetal heart quantification (Fetal HQ) technology is a new speckle tracking technology that can analyze the 24-segment morphology and function of fetal ventricles. This study aims to use Fetal HQ to assess the changes in the structure and function of the fetal heart in normal mid to late pregnancy, providing a foundation for the clinical application of fetal cardiac speckle tracking technology. The heart size, global sphericity index (GSI), left ventricular [stroke volume (SV)], cardiac output (CO), ejection fraction (EF), global longitudinal strain (GLS), fractional area change (FAC), 24-segment end-diastolic diameter (EDD), sphericity index (SI) and fractional shortening (FS) of the two ventricles of 500 normal pregnant fetuses were evaluated by Fetal HQ. The subjects were divided into 5 groups according to gestational weeks (GA), and the changes of fetal heart morphology and function were observed. P<0.05 indicated the statistically significant difference. The fetal heart rate decreased gradually with the increase of GA (P<0.05). The size parameters of the fetal heart and two ventricles gradually increased with increasing GA (P<0.05). The 24 segments EDD of both ventricles increased with increasing GA (P<0.05), while the EDD increased first and then decreased from the ventricle base to the apex. The GSI and the 24 segments SI of two ventricles were basically not significantly different among the groups (P>0.05). The EF, GLS, FAC of the left ventricle and the GLS, FAC of the right ventricle decreased with the increase of GA (P<0.05), and SV and CO increased with increasing GA (P<0.05). The 24 segments FS of the left ventricle showed a downward trend with the increase of GA and gradually increased from the base to the apex. The FS of most segments of the right ventricle decreased with the increase of the GA and increased first and then decreased from the base to the apex. The whole and segmental size parameters of fetal heart can quantitatively evaluate the growth and development of fetal heart; the GSI and segmental SI are reliable morphological indexes for evaluating fetal heart; fetal ventricular function parameters EF, FAC, GLS and segmental FS can evaluate fetal cardiac function. The Fetal HQ technique can help us to evaluate the heart growth and development of normal fetuses in the second and third trimester of pregnancy.

Centhaquine Increases Stroke Volume and Cardiac Output in Patients with Hypovolemic Shock.

Introduction: Centhaquine is a resuscitative agent that acts on α2B adrenergic receptors. Its effect on cardiac output in hypovolemic shock patients has not been reported. Methods: This pilot study was conducted in 12 hypovolemic shock patients treated with centhaquine who participated in an open-label phase IV study (NCT05956418). Echocardiography was utilized to measure stroke volume (SV), cardiac output (CO), left ventricular outflow tract velocity time integral (LVOT-VTI) and diameter (LVOTd), heart rate (HR), left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), and inferior vena cava (IVC) diameter before (0 min) and 60, 120, and 300 min after centhaquine (0.01 mg/kg) iv infusion for 60 min. Results: SV was significantly increased after 60, 120, and 300 min. CO increased significantly after 120 and 300 min despite a decrease in HR. IVC diameter and LVOT-VTI at these time points significantly increased, indicating the increased venous return. LVEF and LVFS did not change, while the mean arterial pressure (MAP, mmHg) increased after 120 and 300 min. Positive correlations between IVC diameter and SV (R2 = 0.9556) and between IVC diameter and MAP (R2 = 0.8928) were observed, which indicated the effects of an increase in venous return on SV, CO, and MAP. Conclusions: Centhaquine-mediated increase in venous return is critical in enhancing SV, CO, and MAP in patients with hypovolemic shock; these changes could be pivotal for reducing shock-mediated circulatory failure, promoting tissue perfusion, and improving patient outcomes. Trial Registration: CTRI/2021/01/030263 and NCT05956418.