Left Ventricular Load Research Articles

Ventricular-arterial coupling: Advances and current perspectives in cardiovascular research

The concept of ventricular-arterial coupling (VAC) was first introduced in the early 1980s to quantify the relationship between left ventricular contractility and arterial load. The mathematical formulation of VAC, expressed as the ratio of arterial elastance to ventricular elastance, has since then been refined with adjustments to allow for non-invasive assessment. By the early 2000s, advancements in echocardiography, cardiac magnetic resonance and arterial tonometry provided non-invasive alternatives to the traditional invasive method of cardiac catheterization, broadening the clinical application of VAC. Emerging technologies, such as machine learning and computational models, have further enhanced the precision and personalization of VAC, with potential applications in heart failure, hypertension and other clinical scenarios.<br /> This review describes the physiological basis and the historical development of VAC, highlights the non-invasive assessment techniques, and discusses the potential for personalized treatment based on VAC insights. Machine learning models trained on large datasets from non-invasive imaging modalities may open new avenues in predicting individual patient responses to therapies. However, lack of standardized protocols across imaging modalities represents a challenge, making the call for standardization critical for consistent clinical application. This review underscores the need for harmonized methodologies to better utilize VAC in personalized medicine, aiming to improve cardiovascular outcomes through tailored therapies.

Circulating factors, in both donor and ex-vivo heart perfusion, correlate with heart recovery in a pig model of DCD

BackgroundHeart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality. MethodsCirculatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 min. Hearts were explanted and underwent ex-situ perfusion for 3h in an unloaded mode, followed by left ventricular loading for 1h, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy. ResultsCirculating adrenaline, both in the donor and at 10 min ex-situ heart perfusion, negatively correlated with cardiac recovery (p <0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p <0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 min. ConclusionsIn heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.

Cardiac Loading using Passive Left Atrial Pressurization and Passive Afterload for Graft Assessment.

Ex vivo machine perfusion or normothermic machine perfusion is a preservation method that has gained great importance in the transplantation field. Despite the immense opportunity for assessment due to the beating state of the heart, current clinical practice depends on limited metabolic trends for graft evaluation. Hemodynamic measurements obtained from left ventricular loading have garnered significant attention within the field due to their potential as objective assessment parameters. In effect, this protocol provides an easy and effective manner of incorporating loading capabilities to established Langendorff perfusion systems through the simple addition of an extra reservoir. Furthermore, it demonstrates the feasibility of employing passive left atrial pressurization for loading, an approach that, to our knowledge, has not been previously demonstrated. This approach is complemented by a passive Windkessel base afterload, which acts as a compliance chamber to maximize myocardial perfusion during diastole. Lastly, it highlights the capability of capturing functional metrics during cardiac loading, including left ventricular pulse pressure, contractility, and relaxation, to uncover deficiencies in cardiac graft function after extended periods of preservation times (˃6 h).

Abstract Mo100: Predictive Accuracy of Rightward Extrapolation of the Left Ventricular End-Diastolic Pressure-Volume Relationship in Healthy Swine

Objective: Myocardial stiffness is a primary determinant of left ventricular (LV) diastolic function and can be quantitatively described by the end-diastolic pressure-volume relationship (EDPVR). The EDPVR is traditionally derived by measuring LV end-diastolic pressure (EDP) and volume (EDV) during transient reductions in venous return (preload). However, the accuracy of this approach in predicting changes in LVEDP in response to a rise in LVEDV via rightward extrapolation has not been directly studied. Accordingly, we sought to assess the predictive accuracy of preload reduction-derived EDPVRs in estimating LV diastolic stiffness (ΔLVEDP/ΔLVEDV) in healthy swine. Methods: LVEDP and LVEDV were measured in swine (n=6) at rest and during transient inferior vena cava (IVC) occlusion (reduced preload), transient aortic occlusion (increased afterload), and intravenous phenylephrine (PE; 0.5 mg/kg/hr; increased afterload and preload). Pressure-volume data collected during IVC occlusion were used to generate the EDPVR, the accuracy of which was determined via comparison to measurements of ΔLVEDP/ΔLVEDV during aortic occlusion and PE. Results: The LV diastolic stiffness coefficient was greater when derived via aortic occlusion vs. IVC occlusion (0.057±0.013 vs. 0.022±0.004; p=0.03). As a result, IVC occlusion-derived EDPVRs underestimated the rise in LVEDP during aortic occlusion (7.6±2.2 vs. 13.5±2.1 mmHg; p=0.08). Similarly, ΔLVEDP/ΔLVEDV in response to aortic occlusion (0.96±0.28 mmHg/mL) tended to be higher than that predicted from the IVC occlusion-derived EDPVR (0.44±0.09 mmHg/mL; p=0.12). Compared with aortic occlusion, PE elicited a greater rise in LVEDV (31.5±5.4 vs.18.6±4.2 mL; p=0.08) and LVEDP (20.8±1.3 vs. 13.5±2.1 mmHg; p=0.01) but ΔLVEDP/ΔLVEDV was comparable between each condition (0.78±0.16 mmHg/mL vs. 0.96±0.28 mmHg/mL; p=0.60). However, ΔLVEDP/ΔLVEDV derived from PE tended to be higher than that from IVC occlusion (0.78±0.16 mmHg/mL vs. 0.44±0.09 mmHg/mL; p=0.10). Conclusions: Rightward extrapolation of the EDPVR derived via IVC occlusion underestimates the rise in LVEDP when LVEDV is increased in the normal heart. This was observed with increased afterload as well as when afterload and preload were simultaneously increased via PE. These findings reinforce the importance of assessing the hemodynamic response to increased LV loading directly, rather than extrapolating from EDPVRs created via transient preload reduction.

The influence of perceived discrimination on aortic hemodynamics in young Black adults

Black adults experience the greatest prevalence of cardiovascular disease (CVD) risk factors and higher CVD mortality of any racial or ethnic group in the United States. The chronic stress from experiencing racial discrimination may exert a weathering effect that contributes to cardiovascular health inequities observed among Black adults. Prior evidence has suggested that Black adults experience greater aortic stiffness as compared with white adults. However, there is limited information regarding perceived racial discrimination and aortic hemodynamics in young adults. Purpose/Hypothesis: The purpose of this study was to determine whether perceived racial discrimination was associated with worse aortic hemodynamics in young Black adults. Methods: Black adults aged 18-25 (n=18, 44% female) volunteered to participate in this study. Participants arrived at the lab at 7:00AM in a fasted state. Following 30 minutes of rest, central pressure waveforms were derived from the radial artery waveform acquired via applanation tonometry and the use of the generalized transfer function. We report aortic augmentation pressure (AP, mmHg), augmentation index (AIx, %), augmentation index normalized to a heart rate of 75bpm (AIx75), round trip transit time (Tr, ms), and the subendocardial viability ratio (SEVR, %), also known as the Buckberg Index. Peak oxygen consumption (VO2 peak) was measured via Indirect calorimetry during a graded treadmill test. Participants completed a questionnaire that assessed personal-level and group-level discrimination. Partial correlations (Pearson’s r controlled for VO2 peak) were used to assess the association between perceived racial discrimination and aortic hemodynamics. Results: Perceived group-level discrimination was positively associated with AP (r = 0.571, p = 0.026), AIx (r = 0.580, p = 0.023), and AIx75 (r = 0.571, p = 0.026), signifying worse central hemodynamics that are indicative of increased left ventricular systolic load. However, perceived personal-level discrimination was not associated with aortic hemodynamics (ps&gt;0.05). VO2peak was positively associated with Tr (r = 0.511, p = 0.043), signifying a later return of the reflected wave (i.e, better) to the heart to facilitate coronary perfusion during diastole. VO2 peak was also inversely associated with AIx75 (r = -0.657, p = 0.006). Conclusion: These preliminary data indicate that young Black adults who report higher group-level discrimination have an increased left ventricular systolic afterload in the aorta. Future studies investigating coping strategies or the effects of increased fitness to improve central hemodynamics in Black adults are warranted. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death.

Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects. Using a rat model of donation after circulatory death, hearts underwent insitu ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω-nitro-L-arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω-nitro-L-arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels. HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts.

The influence of transcatheter aortic valve replacement on left atrial mechanics: a systematic review and meta-analysis.

The morphology and function of the left atrium (LA) are intimately tied to left ventricular loading conditions. Data pertaining to the effect of transcatheter aortic valve replacement (TAVR) on LA function and geometry are scarce. The aim of the study was to quantify associations between TAVR and LA remodelling by pooling available data from published observational studies. A systematic review and meta-analysis were performed. Studies reporting serial LA speckle-tracking echocardiographic (STE) data, before and after TAVR, were included. Other outcome data included LA area and indexed volume (LAVi) and standard chamber measurements. Outcomes were stratified by timing of follow-up echocardiography: early (<6 months) or late (≥6 months). Twelve studies were included, comprising 1066 patients. The mean reduction in LAVi was 2.72 mL/m2 [95% confidence interval (CI) 1.37-4.06, P < 0.01]. LA reservoir function improved overall by a mean difference (MD) of 3.71% (95% CI 1.82-5.6, P < 0.01), although there was significant heterogeneity within the pooled studies (I 2 = 87.3%). Significant improvement in reservoir strain was seen in both early follow-up (MD 3.1%, P < 0.01) and late follow-up studies (MD 4.48%, P = 0.03), but heterogeneity remained high (I 2 = 65.23 and 94.4%, respectively). Six studies reported a change in LA contractile function, which recovered in the early follow-up studies (MD 2.26, P < 0.01), but not in the late group (MD 1.41, P = 0.05). Pooled improvement in LA booster function was 1.96% (95% CI 1.11-2.8, P < 0.01). TAVR is associated with significant negative LA remodelling, and an improvement in LA mechanics, quantified by STE. The prognostic implications of these findings require further study.

Rescuing the Right Ventricle: Mechanical Support After Pediatric Heart Transplantation

BackgroundRight ventricular (RV) failure after heart transplantation (HT) is common in those with pretransplantation elevated pulmonary vascular resistance (PVR). Mechanical circulatory support has been used as a bridge to recovery, with mixed outcomes. We describe a patient with failed single-ventricle palliation in whom severe RV failure developed after HT. We review the current literature and outline our post-HT strategy. MethodsAn infant with trisomy 21, severely unbalanced right dominant atrioventricular septal defect, and hypoplastic aortic arch was palliated with a hybrid procedure. At 6 months of age, cardiac catheterization measured PVR index of 5.47 Wood units × m2 on maximal medical therapy. The patient was deemed unsuitable for second-stage palliation and underwent HT at 18 months of age. Despite preemptive medical therapies, acute RV failure developed, necessitating extracorporeal membrane oxygenation. He was quickly converted to main pulmonary artery to left atrial cannulation. Unloaded RV function normalized; he was weaned from support and discharged home 5 weeks after HT. ResultsFailure of medical therapy in RV failure after HT requires escalation to mechanical circulatory support. We review the literature on RV failure and support after HT. We also describe a novel cannulation strategy to provide a reliable way to directly reduce RV afterload, to allow physiologic training of the right ventricle to a higher PVR, and to maintain normal left ventricular coupling and loading. ConclusionsIn pediatric patients with elevated PVR undergoing HT, advanced therapies can be used effectively to treat acute RV failure. Unique cannulation strategies may play a role in improving survival of similar patients.

The effect of intra-aortic balloon pumping on hemodynamics and left ventricular load in Impella-supported condition: A simulation study

Abstract Introduction Intra-aortic balloon pumping (IABP) is a commonly used percutaneous mechanical circulatory support device. Although IABP combined with Impella, a percutaneous left ventricular assist device, has shown positive outcomes in a few case reports of acute heart failure, its hemodynamic and left ventricular (LV) unloading effects remain unclear. Purpose We conducted a simulation study to clarify the clinical benefits of adding IABP to Impella-supported conditions. Methods We used SimulinkⓇ for cardiovascular simulation. The systemic and pulmonary circulation were modelled by using a 5-element resistance-capacitance network with four ventricles represented by time-varying elastance and unidirectional valves (Figure 1A). We compared total systemic flow, coronary perfusion pressure (CPP), and pressure-volume relationships (PV loop) in severe LV dysfunction (LV end-systolic elastance: 0.2 mmHg/mL) under three scenarios: IABP with a 40 mL balloon volume added to baseline, IABP added to Impella CP support at P2 (partial support) and P8 (total support) (Figure 1B). Results As shown in Figure 2A, IABP increased total systemic flow and CPP, and shifted the PV loop to the left. In P2-Impella condition, the addition of IABP increased native cardiac output (0.3 to 0.7 L/min) and total systemic flow (2.7 to 2.9 L/min), while decreased Impella pump flow due to increased afterload of Impella during diastole. IABP further moved PV loop leftward and reduced LV pressure-volume area (PVA) by -3.8% from Impella only and -7.8% from baseline (Figure 2B). In P8-Impella condition, IABP did not change total systemic flow, CPP, or PV loop (Figure 2C). Conclusions The addition of IABP to Impella could increase CPP while increasing Impella pump afterload and decreasing Impella flow. Overall, IABP slightly increased total systemic flow and decreased LV workload in Impella partial support condition. In specific clinical situations, IABP has the potential to be used as adjuvant therapy alongside Impella partial support.Figure 1

Abstract 18337: Myocardial Work - A Novel Approach to Investigate the Effects of Right Ventricular Apical Pacing on Left Ventricular Regional Work and Function

Background: Right ventricular pacing (RVp) is the most common method of delivering bradycardia pacing, but it is associated with left ventricular (LV) systolic dysfunction (LVSD) in 40% of patients. Animal models have shown that RVp-induced electrical conduction delay leads to dyssynchronous LV activation, resulting in uneven myocardial work (MW) distribution. This work redistribution is believed to trigger adaptive structural remodelling, aiming to achieve a more uniform LV load distribution. Cardiac resynchronisation therapy (CRT) responders demonstrate normalised MW distribution and baseline constructive MW measurements may predict CRT response. However, there is limited evidence on MW in patients with pacemakers. Hypothesis: Long-term RVp in atrioventricular block (AVB) patients with pacemakers may influence MW. Method and Results: One hundred and eighteen patients (mean age 75±10 years; 69% male) with AVB receiving pacemaker therapy were included. Echocardiographic assessment and MW calculations were performed pre- and post-implant. LVSD was defined as LVEF &lt;50%. Among patients, 33 (28%) had LVSD at follow-up (mean time 26±19 months). RVp significantly influenced LVEF (F (1, 18) = 1193, p &lt;0.001), while MW changes were evaluated using repeated measures ANOVA. Constructive work showed a significant interaction effect at the septal wall (F (1, 21) = 8.57, p = 0.008), with no changes observed at the lateral wall (F (1, 51) = 0.93, p = 0.35). However, wasted work exhibited significant interaction effects at both the septal and lateral walls (F (1, 21) = 16.30, p &lt;0.001 vs. F (1, 51) = 7.10, p = 0.014, respectively) (Figure 1). Conclusion: Constructive and wasted work measures at septal and lateral walls are associated with LVSD in patients receiving a pacemaker for AVB. MW may add additional predictive value in identifying people at risk of developing RVp-associated LVSD who may benefit from more complex device therapy such as conduction system pacing, or CRT.

Abstract 18806: How Well Does Left Atrial Remodeling Predict Adverse Outcomes in Patients With Chronic Severe Aortic Regurgitation?

Introduction: Aortic regurgitation (AR) leads to left ventricular (LV) remodeling by increasing LV load. We recently showed that LV dimensions, widely adopted marker of severe AR, are not reliable predictors of adverse CV outcomes in older patients and female sex. Here we sought to study the effects of chronic severe AR on left atrial (LA) size and function as a prognostic adjunct to LV dimensions. Methods: Adult patients with ≥3+ AR on routine surveillance with serial echocardiograms between 1/2010 and 12/2016 were included in this study. We assessed longitudinal trends of LA volume indexed to body surface area (LAVI) and LA reservoir strain (LAr) stratified by age and sex. Clinical endpoints included the occurrence of heart failure hospitalization, urgent aortic valve surgery, or all-cause mortality and were used to assess the prognostic value of our studied parameters. Results: A total of 525 patients with 1,687 serial echocardiograms conducted over a median (IQR) follow-up duration of 2.0 (1.0-3.6) years were included. As shown in figure 1, we observed a substantial increase in LAVI (1.0 [95% CI: 0.76-1.2] mL/m2 per year of follow-up) and a decrease in LAr (-1.3% [95% CI: -1.6 to -0.92%]) over the study period. There was no significant interaction related to sex or age (p ≥0.17). 210 adverse events were recorded and were significantly predicted by both LA parameters. Optimal discriminatory threshold for LAVI was determined to be 37 mL/m2 and LAr at 35% and were both found to be consistent across categories of sex and age. Conclusions: This study indicates that LA remodeling, unlike LV remodeling, shows a similar rate of progression across different categories of sex and age among patients with chronic severe AR. Furthermore, LA parameters provide an added prognostic value over LV parameters and may therefore be better suited to inform the timing of AR intervention.

Abstract 16954: Sex Differences in Cardiac and Vascular Function With Healthy Aging: Implications for Greater Risk of HFpEF in Women

Introduction: Mechanisms mediating the disproportionate risk for heart failure with preserved ejection fraction (HFpEF) in women are poorly understood. Impaired stroke volume (SV) reserve, increased afterload, arterial and left ventricular (LV) stiffness contribute to exercise intolerance in HFpEF. It is unknown whether subclinical changes in these measures predispose women to HFpEF; therefore, we compared resting and exercise cardiovascular structure and function across age in healthy men and women. Methods: We studied 192 sedentary normotensive, non-obese adults (53% female; age: 58 ± 13 [20-90] years) at rest, during sub- and maximal exercise. We measured systolic blood pressure (SBP; electrosphygmomanometry) and aortic stiffness (carotid-femoral pulse wave velocity; aPWV). Myocardial stiffness was assessed as the slope of individual pressure-volume (right heart catheterization-echocardiography) curves generated by graded LV loading and unloading. SV was calculated from cardiac output (Q˙c; C 2 H 2 rebreathe)/heart rate to assess afterload (Ea; SBP/SV) and SV reserve (% change from rest) during exercise. Data were compared via two-way ANOVA (age*sex). Results: There was no significant age*sex interaction for aPWV, SV reserve, resting or maximal SBP, or myocardial stiffness; however, there was a main effect for sex with higher myocardial stiffness in women (Figure). aPWV and SV reserve were not different between sexes (p=0.349, p=0.940). Maximal exercise SBP was lower in women, but a similar proportion of each sex had an exaggerated maximal exercise SBP (Men: &gt;210; Women: &gt;190 mmHg; 28% vs 35%, χ 2 =0.290). Peak exercise afterload was higher in women (Figure) due to lower SV. Conclusions: Increased risk for HFpEF in women may be driven in part by greater myocardial stiffness throughout the aging process. Sex related abnormalities in afterload were most prominent with exercise in women, which may predispose to LV hypertrophy and increased stiffness.

Effect of acute handgrip and aerobic exercise on wasted pressure effort and arterial wave reflections in healthy aging.

Aging increases arterial stiffness and wave reflections that augment left ventricular wasted pressure effort (WPE). A single bout of exercise may be effective at acutely reducing WPE via reductions in arterial wave reflections. In young adults (YA) acute aerobic exercise decreases, whereas handgrip increases, wave reflections. Whether acute exercise mitigates or exacerbates WPE and arterial wave reflection in healthy aging warrants further examination. The purpose of this study was to determine if there are age-related differences in WPE and wave reflection during acute handgrip and aerobic exercise. When compared with baseline, WPE increased substantially in older adults (OA) during handgrip (5,219 ± 2,396 vs. 7,019 ± 2,888 mmHg·ms, P < 0.001). When compared with baseline, there was a robust reduction in WPE in OA during moderate-intensity aerobic exercise (5,428 ± 2,084 vs. 3,290 ± 1,537 mmHg·ms, P < 0.001), despite absolute WPE remaining higher in OA compared with YA during moderate-intensity aerobic exercise (OA 3,290 ± 1,537 vs. YA 1,188 ± 962 mmHg·ms, P < 0.001). There was no change in wave reflection timing indexed to ejection duration in OA during handgrip (40 ± 6 vs. 38 ± 4%, P = 0.41) or moderate-intensity aerobic exercise (40 ± 5 vs. 42 ± 8%, P = 0.99). Conversely, there was an earlier return of wave reflection in YA during handgrip (60 ± 11 vs. 52 ± 6%, P < 0.001) and moderate-intensity aerobic exercise (59 ± 7 vs. 51 ± 9%, P < 0.001). Changes in stroke volume were not different between groups during handgrip (P = 0.08) or aerobic exercise (P = 0.47). The greater increase in WPE during handgrip and decrease in WPE during aerobic exercise suggest that aortic hemodynamic responses to acute exercise are exaggerated with healthy aging without affecting stroke volume.NEW & NOTEWORTHY We demonstrated that acute aerobic exercise attenuated, whereas handgrip augmented, left ventricular hemodynamic load from wave reflections more in healthy older (OA) compared with young adults (YA) without altering stroke volume. These findings suggest an exaggerated aortic hemodynamic response to acute exercise perturbations with aging. They also highlight the importance of considering exercise modality when examining aortic hemodynamic responses to acute exercise in older adults.

Myocardial Work in Middle-Aged Adults with Overweight and Obesity: Associations with Sex and Central Arterial Stiffness.

We explored global myocardial work index (GWI), a novel measure of myocardial function that integrates left ventricular (LV) hemodynamic load, in relation to sex and increased body mass index (BMI). We used data from 467 individuals (61% women, average age 47 ± 9 years and BMI 31.2 kg/m2) without known cardiac disease. Central arterial function was analysed by applanation tonometry. GWI was calculated from global longitudinal strain (GLS) and post-echocardiography supine blood pressure (BP). Covariables of GWI were identified in linear regression analyses. Women had higher BMI, aortic augmentation pressure (12 ± 7 vs. 8 ± 6 mmHg), LV GLS (20.0 ± 2.8 vs. 18.8 ± 2.8%), and GWI (2126 ± 385 vs. 2047 ± 389 mmHg%) than men (all p < 0.05). In univariable analyses, higher GWI was associated with female sex, higher age, systolic BP, LV wall stress, LV ejection fraction, left atrial size, LV ejection time, and with lower waist circumference (all p < 0.05). In multivariable analysis, adjusting for these correlates, female sex remained independently associated with higher GWI (β = 0.13, p = 0.007). After additional adjustment for aortic augmentation pressure or central pulse pressure, this association became non-significant. In conclusion, the higher GWI in women compared to men was mainly explained by increased LV workload due to higher aortic augmentation pressure in women.

A Novel Speckle-Tracking Echocardiographic Parameter Assessing Left Ventricular Loading During VA ECMO in a Pre-clinical Model of Cardiogenic Shock

A Novel Speckle-Tracking Echocardiographic Parameter Assessing Left Ventricular Loading During VA ECMO in a Pre-clinical Model of Cardiogenic Shock

The change in propagation speed of natural shear waves by altering preload might differentiate patients with increased myocardial stiffness

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders - FWO. Background Shear wave (SW) elastography (SWE) is a novel ultrasound-based technique for the assessment of myocardial stiffness. SWE tracks the propagation of SWs travelling through the myocardium, induced by e.g. mitral valve closure (MVC). The speed of SWs is related to myocardial stiffness. As myocardial stiffness is defined by a non-linear stress-strain relation, it is dependent on the operating stress levels and thus left ventricular (LV) loading. As a result, elevated SW speed values could be caused by both increased LV preload or structural remodelling of the myocardium. In this way, performing SWE measurements at different loading states could potentially provide additional information aiding with the interpretation of these measurements. Purpose to investigate if performing SWE before and after a loading change could provide more information on tissue properties of the myocardium. Methods Twelve patients [age: 76(41–82)] receiving intermittent hemodialysis (HD) and 12 age-matched healthy volunteers [age: 67(47–71); p = 0.19] were included. Patients were scanned before and 1 hour after the start of HD. Parasternal long-axis views were acquired using an experimental ultrasound scanner with an average frame rate of 1086±185 Hz. Patients were divided into 2 equal groups based on the grade of diastolic dysfunction (DD), determined using conventional echo parameters (group 1: DD grade 0–1 and group 2: DD grade 2−3). SWs after MVC were visualized on M-mode maps along the septum which were colour coded for tissue acceleration (Figure A). The speed was semi-automatically calculated by measuring the slope of the SW. Results The average ultra-filtrated volume after 1h of HD was 0.64±.27 L, which did not significantly differ between patient groups (p = 0.44). Patients in group 2 had significantly higher indexed LV wall mass compared to group 1 (128±39 g/m² vs. 72±24 g/m²; p = 0.02), indicative of LV structural remodelling. SW speed after MVC was significantly different between healthy volunteers and the patient groups at baseline (p&amp;lt;0.01) (Figure B). After 1h of HD, SW speed decreased in both groups, with the largest decrease in group 2 (Figure B). Furthermore, SW speed values of patient group 1 decreased to values similar to healthy volunteers, while patient group 2 still had significantly increased SW propagation speed. Conclusions Overall, myocardial stiffness, assessed using SW propagation speed, of patients with end-stage kidney disease was increased compared to healthy volunteers. This could result from increased LV preload or structural remodelling. Our data indicate that in addition to single measurements, assessing the change in SW speed by altering the loading state might aid in differentiating these causal mechanisms underlying increased myocardial stiffness. Therefore, adding a loading challenge, e.g. leg lifting, when doing SWE could provide additional information. Further research needs to confirm these initial findings.

Cardiac troponin T predicts future lower left ventricular systolic function and synchrony assessed by cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Akershus University Hospital Trust and Vestre Viken Hospital Trust. Roche Diagnostics provided reagents for high sensitivity cardiac troponin T analyses free of charge. Background In the general population, higher concentrations of cardiac troponin T (cTnT) are associated with risk of cardiovascular (CV) disease even within the normal range. Cardiac magnetic resonance (CMR) offers state-of-the-art assessment of the left ventricle with recently developed techniques allowing assessment of myocardial strain and synchrony. There is little prospective observational data describing the association between cTnT and future left ventricular (LV) function assessed by CMR. Purpose To investigate whether cTnT is predictive of future lower LV systolic function and synchrony in the general population. Methods The cohort included 186 participants from the general population who underwent cTnT measurements at baseline followed by CMR feature-tracking 4–7 years later. All participants were born in year 1950, had no overt coronary artery disease and normal kidney function at inclusion. Outcomes were LV global longitudinal, circumferential and radial strain (GLS, GCS and GRS), as well as mechanical dispersion (MD). MD was calculated as the standard deviation of time to peak longitudinal strain of 16 left ventricular segments adjusted for heart rate. Associations between cTnT concentrations and outcomes were evaluated using linear regression with cTnT modeled as (1) a continuous variable and (2) dichotomized at the level of detection (≥ 3.0 ng/L). Models adjusted for a priori selected confounders influencing CV risk and cTnT concentrations were obtained (model 1: sex, age and estimated glomerular filtration rate; model 2: additionally, hypertension, body mass index, diabetes mellitus and daily smoking). An extended adjustment model included metrics affecting LV loading conditions (model 3: systolic blood pressure, heart rate and end diastolic volume indexed by body surface area at the time of CMR), as well as QRS duration for MD. Results Participants with detectable cTnT had significantly lower absolute GLS, GCS and GRS and higher MD than those with undetectable cTnT (Table 1). The detectable cTnT group had a greater proportion of males, a higher prevalence of hypertension, lower kidney function and was slightly younger at inclusion. Higher cTnT concentrations were independently associated with lower absolute GLS, GCS and GRS and higher MD in both risk factor adjusted models (table 2). For detectable cTnT, similar associations were found in model 1 but the association between detectable cTnT and MD was attenuated in model 2. In the fully adjusted model 3 both detectable and continuous cTnT concentrations remained associated with lower absolute GLS, whereas only detectable cTnT was associated with lower absolute GCS and GRS. Conclusion Higher cTnT, largely within the normal range, is predictive of future lower LV systolic function and synchrony assessed by CMR in a general middle-aged population.

Differences in Left Ventricular Enlargement Secondary to Chronic Volume Loading Between English Springer Spaniels and Two Similar Sporting Breeds

IntroductionEnglish springer spaniels have larger, rounder ventricles than most other breeds. How this geometry impacts responses to volume overload remains unknown. We compared left ventricular size between English springer spaniels and two similarly sized sporting breeds (Border collies and Labrador retrievers) in naturally occurring chronic left ventricular volume loading conditions (mitral regurgitation and patent ductus arteriosus [PDA]) to examine whether differences in remodelling responses exist between these breeds. Animals, materials and methodsWe searched records for cases of mitral regurgitation and PDA in three breeds. We recorded age, sex, presence of congestive heart failure (CHF), body weight and specific echocardiographic variables. We compared normalised measures of left ventricular size between breeds. Cases with CHF were further examined as a separate group. ResultsOne-hundred-and-ninety-one dogs were included: 110 with degenerative mitral valve disease, 42 with mitral dysplasia and 39 with PDA. One third of all cases had CHF. All measures of left ventricular size were larger in English springer spaniels in mitral regurgitation cases (P<0.001), whereas PDA cases did not differ. English springer spaniels with PDA resulting in CHF had larger systolic dimensions and volumes than similarly affected non-English Springer Spaniel dogs (P=0.003). ConclusionsEnglish springer spaniels have greater left ventricular dimensions when exposed to chronic mitral regurgitation, compared with Border collies and Labrador retrievers, but not when exposed to volume overload from a PDA. English springer spaniels differ in their left ventricular morphology from two other sporting breeds, supporting previous studies that they have a unique cardiac morphotype.

P73: Subclavian Artery Cannulation For Left Ventricular Unloading During Extracorporeal Membrane Oxygenation Support

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective mechanical circulatory support for cardiac insufficiency following cardiac surgery especially cardiac surgery with extracorporeal circulation, which can quickly restore the perfusion of vital organs. However, retrograde blood flow in the aorta during VA-ECMO may lead to increased left ventricular (LV) afterload, elevated LV filling pressure, mitral insufficiency, and elevated left atrial pressure, which may subsequently result in reduced coronary blood flow and pulmonary edema, thus aggravating the patient’s condition. Therefore, LV unloading is necessary during VA-ECMO. The optimal approach for LV unloading remains undefined, but the percutaneous access has been increasingly used over time. To addresss this issue, we have attempted to use cannulation of the subclavian artery for left ventricular unloading during VA-ECMO. This study aims to describe our method and report the preliminary results in three patients. Methods: Three patients with low cardiac output syndrome after cardiac surgery. All 3 patients had difficulty weaning from cardiopulmonary bypass (CPB) due to overfilling and contractile weakness of the heart, low mean arterial pressure<80mmHg, and left atrial pressure of >20 mmHg. Decision was made to start ECMO support immediately, and LV unloading was initiated via cannulation of the subclavian artery (Table 1). Given the differences in the surgical approaches and condition of patients, three methods were used to achieve LV unloading via the subclavian artery.Methods of LV unloading with cannulation via the subclavian artery during VA-ECMO in three patients with low cardiac output syndrome after cardiac surgery: 1) VA-ECMO with LV unloading via subclavian artery; 2) femoral vein-to-subclavian artery VA-ECMO with LV unloading via a 4-branched graft; 3) LV bypass via femoral artery-subclavian artery. Results: In all patients, the subclavian artery cannula was withdrawn at postoperative days 2-3, and ECMO was successfully weaned on postoperative day 4. One patient developed cardiac tamponade within 24 hour of surgery, echocardiography showed an LVEF of 55%. During an exploratory thoracotomy, a large amount of blood clot about 500 mL was found in the pericardium and removed, and the patient recovered uneventfully. Table 2 summarizes the postoperative courses of the 3 patients with different LV unloading methods. Conclusion: This study partly illustrated that LV drainage via the subclavian artery could safely and effectively reduce the LV load, prevent VA-ECMO-related complications, and minimize the risk of trauma and infection during LV examinations. Certainly, whether the subclavian artery approach is the optimal strategy for LV unloading as well as patient risks and benefits remains to be further investigated.Figure 1. ECMO + LV unloading schematic diagram of Case 1 (femoral artery + femoral vein+ subclavian artery)Figure 2. ECMO + LV unloading schematic diagram of Case 2 (femoral artery + femoral vein + four branches aortic graft)Figure 3. LV unloading schematic diagram of Case 2 (femoral artery + subclavian artery)

The impact of aortic valve regurgitation on the combination therapy of VA-ECMO and Imeplla support in severe cardiogenic shock: a simulation study

Background: The utilization of a combination of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, ECPELLA, has become widespread among patients with cardiogenic shock. The utilization of VA-ECMO in the presence of aortic regurgitation (AR) can result in significant left ventricular (LV) distention. Additionally, the implantation of Impella via the aortic valve frequently induces AR clinically. We established a simulation model and evaluated the impact of AR on hemodynamics under ECPELLA. Furthermore, assuming that the reverse flow of AR is strongly determined by aortic pressure (AP) level, we simulated a scenario where AP was further decreased. Methods: We employed Simulink® (Mathworks, Inc.). The systemic and pulmonary circulations were modeled using a 5-element resistance-capacitance network. Four cardiac chambers were represented by time-varying elastance. We compared the aortic regurgitant flow (Far), total systemic flow (Ftotal), and LV pressure-volume relationship under various severities of AR and varying Impella (0-3.7 L/min) and VA-ECMO (0-5 L/min) flows. AR grades were adjusted by the regurgitant resistance and classified as mild, moderate, and severe, mimicking a clinical scenario. Results: Without AR, ECMO significantly increased Ftotal and raised LV end-diastolic pressure (LVEDP). Impella increased Ftotal and decreased LVEDP. The concomitant presence of AR exacerbated the increase of LVEDP by ECMO and the reduction of LVEDP by Impella. Under ECPELLA support (VA-ECMO: 3 L/min) with mild AR, the increase of Impella support (1 to 3.5 L) increased Ftotal and Far, while decreasing LVEDP, indicating the prevention of AR-induced LV distention. Additionally, the presence of mild AR prevented the Impella-induced left ventricular suction that is commonly observed under ECPELLA support with high-flow VA-ECMO. In the case of moderate AR, while the hemodynamic trends were similar to those observed under mild AR, Impella was unable to prevent the increment of LVEDP to a critical level (&lt; 20 mmHg). However, by decreasing AP through reducing resistance (e.g. vasodilators), both Far and LVEDP were dramatically reduced and Ftotal was increased under ECPELLA support. Conclusion: The concomitant presence of AR in ECPELLA condition increased LV load, while prevented LV suction. The use of vasodilator in ECPELLA with AR could attenuate AR, increase systemic perfusion, and reduce LV load. The optimal control of Impella and VA-ECMO flows and AP can maximize the hemodynamic and LV unloading impacts of ECPELLA. no funding This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.