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Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = −0.31; P = 0.04). TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation. [ABSTRACT FROM AUTHOR]

• Combining information derived from both the amplitude and shape of right ventricular pressure waveform with other data sources provides the basis for a more comprehensive bedside assessment of right ventricular function. Continuous measurement of pressure in the right atrium and pulmonary artery has commonly been used to monitor right ventricular function in critically ill and surgical patients. This approach is largely based upon the assumption that right atrial and pulmonary arterial pressures provide accurate surrogates for diastolic filling and peak right ventricular pressures, respectively. However, due to both technical and physiologic factors, this assumption is not always true. Accordingly, recent studies have begun to emphasize the potential clinical value of also measuring right ventricular pressure at the bedside. This has highlighted both past and emerging research demonstrating the utility of analyzing not only the amplitude of right ventricular pressure but also the shape of the pressure waveform. This brief review summarizes data demonstrating that combining conventional measurements of right ventricular pressure with variables derived from waveform shape allows for more comprehensive and ideally continuous bedside assessment of right ventricular function, particularly when combined with stroke volume measurement or 3D echocardiography, and discusses the potential use of right ventricular pressure analysis in computational models for evaluating cardiac function. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The subjects of this study were 158 patients (68 males and 90 females, mean age 74.8 ± 11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had a significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e′, and E/e′ (p < 0.001, respectively). Multivariate logistic regression analysis revealed that higher PWV values and hypertension were significant predictors for the dependent factor (HFpEF). Arterial stiffness amplified afterload, leading to LV concentric hypertrophy and diastolic dysfunction. This study presents that arterial stiffness is a key predictor of HFpEF, and that phosphate retention is involved in the pathology of HFpEF. [ABSTRACT FROM AUTHOR]

It remains unclear why some patients develop heart failure without evidence of structural damage. One theory relates to impaired myocardial energetics and ventricular-arterial decoupling as the heart works against adverse mechanical load. In this original study, we propose the novel concept of myocardial fatigue to capture this phenomenon and aim to investigate this using human cardiomyocytes subjected to a modern work-loop contractility model that closely mimics in vivo cardiac cycles. This proof-of-concept study (NCT04899635) will use human myocardial tissue samples from patients undergoing cardiac surgery to develop a reproducible protocol to isolate robust calcium-tolerant cardiomyocytes. Thereafter, work-loop contractility experiments will be performed over a range of preload, afterload and cycle frequency as a function of time to elicit any reversible reduction in contractile performance (i.e. fatigue). This will provide novel insight into mechanisms behind heart failure and myocardial recovery and serve as a valuable research platform in translational cardiovascular research. [ABSTRACT FROM AUTHOR]

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Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty‐five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance‐compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) function is complex as a number of determinants beyond preload, inotropy and afterload play a fundamental role. In particular, arterial elastance (Ea), ventriculo-arterial coupling (VAC), and (systolic) ventricular interdependence play a vital role for the right ventricle. Understanding and actively visualizing these interactions in the failing RV as well as in the altered hemodynamic and morphological situation of left ventricular assist device (LVAD) implantation may aid clinicians in their understanding of RV dysfunction and failure. While, admittedly, hard data is scarce and invasive pressure-volume loop measurements will not become routine in cardiac surgery, we hope that clinicians will benefit from the comprehensive, simulation-based review of RV pathology. In particular, the aim of this article is to first, address and clarify the pathophysiologic hemodynamic factors that lead to RV dysfunction and then, second, expand upon this basis examining the changes occurring by LVAD implantation. This is illustrated using Harvi software which shows elastance, ventricular arterial coupling, and ventricular interdependence by simultaneously showing pressure volume loops of the right and left ventricle. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the mechanisms and clinical implications of mitral regurgitation (MR) in patients with severe aortic stenosis (AS) who received transcatheter aortic valve replacement (TAVR). Methods: We conducted retrospective echocardiographic analyses at baseline and 6 months after TAVR in 140 patients with symptomatic AS (85 ± 5 years) who underwent TAVR. We defined significant MR as ≥ moderate based on evaluation of transthoracic echocardiography (TTE). Results: There were 48 patients (34%) with preexisting MR at the baseline. Among measured TTE parameters, end‐systolic wall stress (ESWS), mitral annulus area, and mitral valve thickening index were independent factors associated with preexisting MR (odds ratio [OR]: 1.013, 95% confidence interval [CI]: 1.005–1.021; OR: 1.740, 95% CI: 1.314–2.376; OR: 2.306, 95% CI: 1.426–3.848; respectively). Six months after TAVR, there were 34 patients with post‐existing MR, A history of atrial fibrillation and ESWS after TAVR were independent factors (OR: 3.013, 95% CI: 1.208–7.556; OR: 1.013, 95% CI: 1.000–1.023; respectively). The Kaplan–Meier plot indicated that preexisting MR was a risk factor for heart failure–related events within 1 year of discharge after TAVR (p =.012). Conclusions: In patients who underwent TAVR for severe AS, preexisting MR was associated with having a thickened mitral valve and large mitral annulus size induced by high ESWS. These patients may have worse prognosis after TAVR and should be closely monitored in the long term. [ABSTRACT FROM AUTHOR]

Abstract Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty‐five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p

Despite significant advancements in in vitro cardiac modeling approaches, researchers still lack the capacity to obtain in vitro measurements of a key indicator of cardiac function: contractility, or stroke volume under specific loading conditions—defined as the pressures to which the heart is subjected prior to and during contraction. This work puts forward a platform that creates this capability, by providing a means of dynamically controlling loading conditions in vitro. This dynamic tissue loading platform consists of a thin magnetoresponsive hydrogel cantilever on which 2D engineered myocardial tissue is cultured. Exposing the cantilever to an external magnetic field—generated by positioning magnets at a controlled distance from the cantilever—causes the hydrogel film to stretch, creating tissue load. Next, cell contraction is induced through electrical stimulation, and the force of the contraction is recorded, by measuring the cantilever's deflection. Force–length‐based measurements of contractility are then derived, comparable to clinical measurements. In an illustrative application, the platform is used to measure contractility both in untreated myocardial tissue and in tissue exposed to an inotropic agent. Clear differences are observed between conditions, suggesting that the proposed platform has significant potential to provide clinically relevant measurements of contractility. [ABSTRACT FROM AUTHOR]

Engineered cardiac microtissues were fabricated using pluripotent stem cells with a hypertrophic cardiomyopathy associated c. 2827 C>T; p.R943x truncation variant in myosin binding protein C (MYBPC3+/−). Microtissues were mounted on iron-incorporated cantilevers, allowing manipulations of cantilever stiffness using magnets, enabling examination of how in vitro afterload affects contractility. MYPBC3+/− microtissues developed augmented force, work, and power when cultured with increased in vitro afterload when compared with isogenic controls in which the MYBPC3 mutation had been corrected (MYPBC3+/+(ed)), but weaker contractility when cultured with lower in vitro afterload. After initial tissue maturation, MYPBC3+/− CMTs exhibited increased force, work, and power in response to both acute and sustained increases of in vitro afterload. Together, these studies demonstrate that extrinsic biomechanical challenges potentiate genetically-driven intrinsic increases in contractility that may contribute to clinical disease progression in patients with HCM due to hypercontractile MYBPC3 variants. [ABSTRACT FROM AUTHOR]

This study investigated the magnitude and time-course of resistance exercise (RE) technique induced transient cardiac perturbations. Twenty-four participants were assigned to one of four arms: sets to failure or non-failure with 8–10 repetition maximum (RM), and sets to failure or non-failure with 15RM. Echocardiographic and blood pressure (BP) data were recorded at baseline and 30 min, 6 h and 24 h post-exercise. In all groups end-systolic circumferential wall stress (cESS), and ratio of transmitral inflow velocities (E/A) were significantly decreased while posterior wall thickness (PWT), global circumferential strain (GCS), GCS strain rate (GCSR), global longitudinal strain rate (GLSR), and stroke volume (SV) were significantly increased for up to 6 h of follow-up. In the 15RM groups, left ventricular (LV) mass and interventricular septal thickness (IVST) were significantly increased, and left atrial (LA) area was significantly decreased (p < 0.05) compared to the 8–10 RM groups. In the 15RM groups, RE decreased global longitudinal strain (GLS) and increased ejection fraction (EF) (p<0.01). After RE, transient cardiac perturbations, the reduction in LA compliance, and the improvement in LV myofibril geometry were volume dependent and influenced more by sets to failure technique. RE increased GCS and reduced the afterload, thus helping to preserve SV and EF. [ABSTRACT FROM AUTHOR]

Goal: Create a semi-automated, graphical, stand-alone application that uses clinically available asynchronous pressure and Doppler velocity captures to rapidly calculate, display, and interpret the pulmonary vascular impedance (PVZ) spectra. Methods: MATLAB-based software was written to analyze PVZ by creating a composite PVZ (cPVZ) spectra comprised of asynchronous screen captures of pulmonary arterial pressure and pulmonary arterial pulsed-wave Doppler velocity waveforms obtained during standard of care procedures. The pressure waveform, Doppler frequency envelopes, and ECG signals were re-digitized via automated border detection. cPVZ of averaged representative beats was calculated in the frequency domain via Fast Fourier Transform, and plotted vs harmonic z. Results: Successful generation of impedance spectra (PVZ(z)), where z is the harmonic, and additional parameters for characteristic impedance (Zc) and stiffness (Zs) were calculated as the mean of PVZ(2-4), and the sum of PVZ (1, 2), respectively. Conclusions: A graphically driven analysis of PVZ, calculated from standard of care right heart catheterization and echocardiography is possible. This system can help characterize both the steady and pulsatile components of right ventricular (RV) afterload in the clinical setting.

Abstract Despite significant advancements in in vitro cardiac modeling approaches, researchers still lack the capacity to obtain in vitro measurements of a key indicator of cardiac function: contractility, or stroke volume under specific loading conditions—defined as the pressures to which the heart is subjected prior to and during contraction. This work puts forward a platform that creates this capability, by providing a means of dynamically controlling loading conditions in vitro. This dynamic tissue loading platform consists of a thin magnetoresponsive hydrogel cantilever on which 2D engineered myocardial tissue is cultured. Exposing the cantilever to an external magnetic field—generated by positioning magnets at a controlled distance from the cantilever—causes the hydrogel film to stretch, creating tissue load. Next, cell contraction is induced through electrical stimulation, and the force of the contraction is recorded, by measuring the cantilever's deflection. Force–length‐based measurements of contractility are then derived, comparable to clinical measurements. In an illustrative application, the platform is used to measure contractility both in untreated myocardial tissue and in tissue exposed to an inotropic agent. Clear differences are observed between conditions, suggesting that the proposed platform has significant potential to provide clinically relevant measurements of contractility.

Background: In the total artificial heart (TAH), the inputs to the physiological control unit, preload, and afterload, are detected from intrinsic pump parameters (e.g., motor current). Within this study, their detection techniques are developed, and their reliability in pre‐ and afterload prediction is mapped for a broad range of cardiovascular system states. Methods: We used ReinHeart TAH which is a fully implantable TAH with a plunger coil drive that is alternately emptying the left and right chambers. From the coil currents we first derived a force generated by the piston with respect to its position and then analyzed its pattern to detect (1) preload—chamber filling, found as piston position at begin ejection and (2) afterload—mean outflow pressures, determined as linearly calibrated average piston force during ejection. TAH is then integrated into a mock loop circulation (MLC) which is set to 135 different steady operating points varying in chamber filling (0%–100%, five steps), mean outflow pressures (system circulation: 60–90–120 mm Hg, pulmonary circulation: 15–30‐45 mm Hg), and heart cycle duration (171–600 ms in seven non‐equidistant steps). The detected preload and afterload are compared to MLC set values, and the errors are mapped. Results: Respectively for the left and right chambers, the preload was detectable in 134 and 118 operating points and the mean error was ±3% and ±2%. The afterload was detectable in 135 and 87 operating points and the mean error was 37% and 30% respectively for left and right circulation. The operational points that are further away from homeostatic equilibrium values generally yielded larger errors. The largest errors were observed for right circulation at long cycle duration, low afterload, and low filling. Conclusions: The study yields reliable preload estimation in a broad range of physiological states, particularly for left circulation. Detection of afterload needs further improvements. The study revealed a need for piston movement optimization within the ReinHeart TAH during the early phase of systole. [ABSTRACT FROM AUTHOR]

Introduction: While central blood pressure (BP) has been recognized as a major indicator of left ventricular (LV) afterload, the reduction of central pressure decreases LV afterload and may prevent heart failure (HF) decompensation. Noninvasive transcutaneous vagus nerve stimulation (tVNS) was shown to improve cardiac function in HF patients. In this study, the relationship between active tVNS and reduction of central BP was investigated in patients with acute HF (AHF). Methods: The 22 patients hospitalized for AHF after initial stabilization (median 80 yrs, males 60%) were randomly assigned to active or sham group. For 1 h daily over 5 days, low-level transcutaneous electrical stimulation (LLTS) (20 Hz, 1 mA) was performed after attaching an ear clip to the tragus (active group) or the earlobe (sham control group). Before and after stimulation, central aortic systolic pressure (CASP), brachial systolic BP (SBP), diastolic BP (DBP) as well as heart rate (HR) were noninvasively measured. Results: No significant differences in baseline characteristics were observed between the active and sham groups. In the active group, CASP, SBP, DBP, and HR each decreased significantly after stimulation (all p < 0.05), whereas in the sham group, CASP, SBP, DBP, and HR each increased significantly after stimulation (all p < 0.05). All the changes in CASP, SBP, DBP and HR before and after stimulation were also significantly different between active and sham groups (all p < 0.01). There were no device-related side effects. Conclusion: In this study, the left tragus tVNS resulted in an acute afterload reduction in the elderly AHF patients. Non-invasive LLTS may be useful and safe for reducing afterload in AHF. [ABSTRACT FROM AUTHOR]

Abstract Aims Veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V‐A ECMO during the acute and delayed stages of acute myocardial dysfunction. Methods and results A total of 46 adult patients who were supported by peripheral V‐A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V‐A ECMO initiation (n = 45, ‘acute phase’) and mean day 4 ± 2 of V‐A ECMO initiation (n = 36, ‘delayed phase’). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from −6.1 (−8.9 to −4.0)% during 120% TBF to −8.8 (−11.5 to −6.0)% during 50% TBF (P

Lung resection has been shown to impair right ventricular function. Although conventional measures of afterload do not change, surgical ligation of a pulmonary artery branch, as occurs during lobectomy, can create a unilateral proximal reflection site, increasing wave reflection (pulsatile component of afterload) and diverting blood flow through the contralateral pulmonary artery. We present a cardiovascular magnetic resonance imaging (MRI) observational cohort study of changes in wave reflection and right ventricular function after lung resection. Twenty-seven patients scheduled for open lobectomy for suspected lung cancer underwent cardiovascular MRI preoperatively, on postoperative Day 2, and at 2 months. Wave reflection was assessed in the left and right pulmonary arteries (operative and non-operative, as appropriate) by wave intensity analysis and calculation of wave reflection index. Pulmonary artery blood flow distribution was calculated as percentage of total blood flow travelling in the non-operative pulmonary artery. Right ventricular function was assessed by ejection fraction and strain analysis. Operative pulmonary artery wave reflection increased from 4.3 (2.1–8.8) % preoperatively to 9.5 (4.9–14.9) % on postoperative Day 2 and 8.0 (2.3–11.7) % at 2 months (P <0.001) with an associated redistribution of blood flow towards the nonoperative pulmonary artery (r>0.523; P <0.010). On postoperative Day 2, impaired right ventricular ejection fraction was associated with increased operative pulmonary artery wave reflection (r=–0.480; P =0.028) and pulmonary artery blood flow redistribution (r=–0.545; P =0.011). At 2 months, impaired right ventricular ejection fraction and right ventricular strain were associated with pulmonary artery blood flow redistribution (r=–0.634, P =0.002; r=0.540, P =0.017). Pulsatile afterload increased after lung resection. The unilateral increase in operative pulmonary artery wave reflection resulted in redistribution of blood flow through the nonoperative pulmonary artery and was associated with right ventricular dysfunction. NCT01892800. [ABSTRACT FROM AUTHOR]

Abstract Aims Pressure overload (PO) and volume overload (VO) lead to concentric or eccentric hypertrophy. Previously, we could show that activation of signalling cascades differ in in vivo mouse models. Activation of these signal cascades could either be induced by intrinsic load sensing or neuro‐endocrine substances like catecholamines or the renin‐angiotensin‐aldosterone system. Methods and results We therefore analysed the activation of classical cardiac signal pathways [mitogen‐activated protein kinases (MAPKs) (ERK, p38, and JNK) and Akt‐GSK3β] in in vitro of mechanical overload (ejecting heart model, rabbit and human isolated muscle strips). Selective elevation of preload in vitro increased AKT and GSK3β phosphorylation after 15 min in isolated rabbit muscles strips (AKT 49%, GSK3β 26%, P

Background: Increased afterload affects many of the flow dependent metrics assessed during transthoracic echocardiography (TTE) especially in the evaluation valvular disease. A single timepoint blood pressure (BP) may not accurately reflect the afterload present at the time of flow-dependent imaging and quantification. We assessed the magnitude of change in BP at discrete timepoints during routine TTE. Method: We conducted a prospective study where participants underwent automated BP measurement while undergoing a clinically indicated TTE. The first reading was obtained right after the patient lay supine and subsequent readings were taken at 10-min intervals during image acquisition. Result: We included 50 participants (66% were male, with a mean age of 64 years). After 10 min, 40 (80%) participants had a drop in systolic BP of >10 mmHg. Compared to the baseline, there was a significant drop in systolic BP (mean decrease 20.0 ± 12.8 mmHg; P

Cardiac magnetic resonance (CMR) is currently the gold standard for evaluating right ventricular (RV) function, which is critical in patients with pulmonary hypertension. CMR feature-tracking (FT) strain analysis has emerged as a technique to detect subtle changes. However, the dependence of RV strain on load is still a matter of debate. The aim of this study was to measure the afterload dependence of RV strain and to correlate it with surrogate markers of contractility in a cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH) under two different loading conditions before and after pulmonary endarterectomy (PEA). Between 2009 and 2022, 496 patients with 601 CMR examinations were retrospectively identified from our CTEPH cohort, and the results of 194 examinations with right heart catheterization within 24 h were available. The CMR FT strain (longitudinal (GLS) and circumferential (GCS)) was computed on steady-state free precession (SSFP) cine CMR sequences. The effective pulmonary arterial elastance (Ea) and RV chamber elastance (Ees) were approximated by dividing mean pulmonary arterial pressure by the indexed stroke volume or end-systolic volume, respectively. GLS and GCS correlated significantly with Ea and Ees/Ea in the overall cohort and individually before and after PEA. There was no general correlation with Ees; however, under high afterload, before PEA, Ees correlated significantly. The results show that RV GLS and GCS are highly afterload-dependent and reflect ventriculoarterial coupling. Ees was significantly correlated with strain only under high loading conditions, which probably reflects contractile adaptation to pulsatile load rather than contractility in general. [ABSTRACT FROM AUTHOR]

Aims: Veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V‐A ECMO during the acute and delayed stages of acute myocardial dysfunction. Methods and results: A total of 46 adult patients who were supported by peripheral V‐A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V‐A ECMO initiation (n = 45, 'acute phase') and mean day 4 ± 2 of V‐A ECMO initiation (n = 36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from −6.1 (−8.9 to −4.0)% during 120% TBF to −8.8 (−11.5 to −6.0)% during 50% TBF (P < 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8–100.0)% vs. 22.5 (14.9–43.8)%, P < 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1–56.8)% vs. 22.8 (9.2–42.2)%, P = 0.012] and LV outflow tract velocity‐time integral [45.8 (18.6–58.7)% vs. 24.2 (12.6–34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully. Conclusions: We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V‐A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart–ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V‐A ECMO. [ABSTRACT FROM AUTHOR]

Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-β (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokine expression appeared within the first week and decreased to its control level within five weeks. While cardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cells was lower in TRIF−/−mice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent cytokines. Through the modulation of the TGF-β-signaling pathway and anti-fibrotic microRNAs, TRIF was involved in the development of interstitial fibrosis. The absence of TRIF was associated with a decreased expression of proapoptotic proteins. In echocardiography and working heart analyses, TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces the ejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatory cytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiac remodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatory and fibrotic signal transduction pathways. [ABSTRACT FROM AUTHOR]

Objectives: Arginine vasopressin (AVP) is used to treat hypotension. Because AVP increases blood pressure by increasing systemic vascular resistance, it may have an adverse effect on tissue oxygenation following the Norwood procedure. Methods: Retrospective analysis of continuously captured hemodynamic data of neonates receiving AVP following the Norwood procedure. Results: We studied 64 neonates exposed to AVP within 7 days after the Norwood procedure. For the entire group, AVP significantly increased mean blood pressure (2.5 ± 6.3) and cerebral and renal oxygen extraction ratios (4.1% ± 9.6% and 2.0% ± 4.7%, respectively; P

Background: Women have higher risk of heart failure than their male counterparts. Although the mechanical inefficiency of myocardium against an excessive afterload is an important reason of heart failure, little attention has been paid to the sex differences in arterial load and its clinical relevance. Results: The effective arterial elastance index (EaI), total arterial compliance index (TACI), and systemic vascular resistance index (SVRI) were determined using transthoracic echocardiography combined with cuff-measured brachial blood pressure in 460 healthy adults (230 men). The sex differences in these arterial load indexes were analyzed. No statistical difference was found in the age, heart rate, and stroke volume index (all P < 0.05). After adjustment for the cuff-measured blood pressure; the estimated marginal means (95% CIs) of the EaI was higher in women than in men [0.972 (0.952-0.991) vs 0.743 (0.724-0.763) mmHg m²/mL, P < 0.001], the TACI was lower in women than in men [0.924 (0.905-0.944) vs 1.055 (1.036-1.075) mL/mm Hg m², P < 0.001], and no statistical difference was found in the SVRI between sexes (P > 0.05). Conclusions: For any given cuff-measured blood pressure, greater integrated and pulsatile arterial load are imposed on left ventricle in women than in men, which is a piece of evidence that women have higher risk of heart failure than their counterparts. [ABSTRACT FROM AUTHOR]

Conservative management of metachronous second primary carcinoma of head and neck is preferred in order to preserve form and function. The purpose of the case report is to describe the treatment of metachronous second primary carcinoma of soft palate by high‐dose‐rate, remote, afterload brachytherapy. The brachytherapy was done in remote settings by afterloading Iridium 192 isotope carried through a custom fabricated surface mold. The mold enabled good adaptation, stability, and repeatable positioning of the radiation source at each treatment session of fractionated brachytherapy offering consistent dosimetric advantage through a single dosimetry calculation. Collaborative efforts of radiation oncologist and prosthodontist ensured conservative treatment in outpatient set up with minimal adverse effects. [ABSTRACT FROM AUTHOR]

Preload and afterload dictate the dynamics of the cyclical work-loop contraction that the heart undergoes in vivo. Cellular Ca2+ dynamics drive contraction, but the effects of afterload alone on the Ca2+ transient are inconclusive. To our knowledge, no study has investigated whether the putative afterload dependence of the Ca2+ transient is preload dependent. This study is designed to provide the first insight into the Ca2+ handling of cardiac trabeculae undergoing work-loop contractions, with the aim to examine whether the conflicting afterload dependency of the Ca2+ transient can be accounted for by considering preload under isometric and physiological work-loop contractions. Thus, we subjected ex vivo rat right-ventricular trabeculae, loaded with the fluorescent dye Fura-2, to work-loop contractions over a wide range of afterloads at two preloads while measuring stress, length changes, and Ca2+ transients. Work-loop control was implemented with a real-time Windkessel model to mimic the contraction patterns of the heart in vivo. We extracted a range of metrics from the measured steady-state twitch stress and Ca2+ transients, including the amplitudes, time courses, rates of rise, and integrals. Results show that parameters of stress were afterload and preload dependent. In contrast, the parameters associated with Ca2+ transients displayed a mixed dependence on afterload and preload. Most notably, its time course was afterload dependent, an effect augmented at the greater preload. This study reveals that the afterload dependence of cardiac Ca2+ transients is modulated by preload, which brings the study of Ca2+ transients during isometric contractions into question when aiming to understand physiological Ca2+ handling. NEW & NOTEWORTHY This study is the first examination of Ca2+ handling in trabeculae undergoing work-loop contractions. These data reveal that reducing preload diminishes the influence of afterload on the decay phase of the cardiac Ca2+ transient. This is significant as it reconciles inconsistencies in the literature regarding the influence of external loads on cardiac Ca2+ handling. Furthermore, these findings highlight discrepancies between Ca2+ handling during isometric and work-loop contractions in cardiac trabeculae operating at their optimal length. [ABSTRACT FROM AUTHOR]

Background: Women have higher risk of heart failure than their male counterparts. Although the mechanical inefficiency of myocardium against an excessive afterload is an important reason of heart failure, little attention has been paid to the sex differences in arterial load and its clinical relevance. Results: The effective arterial elastance index (EaI), total arterial compliance index (TACI), and systemic vascular resistance index (SVRI) were determined using transthoracic echocardiography combined with cuff-measured brachial blood pressure in 460 healthy adults (230 men). The sex differences in these arterial load indexes were analyzed. No statistical difference was found in the age, heart rate, and stroke volume index (all P < 0.05). After adjustment for the cuff-measured blood pressure; the estimated marginal means (95% CIs) of the EaI was higher in women than in men [0.972 (0.952–0.991) vs 0.743 (0.724–0.763) mmHg m2/mL, P < 0.001], the TACI was lower in women than in men [0.924 (0.905–0.944) vs 1.055 (1.036–1.075) mL/mm Hg m2, P < 0.001], and no statistical difference was found in the SVRI between sexes (P > 0.05). Conclusions: For any given cuff-measured blood pressure, greater integrated and pulsatile arterial load are imposed on left ventricle in women than in men, which is a piece of evidence that women have higher risk of heart failure than their counterparts. [ABSTRACT FROM AUTHOR]

Objective: Left ventricular hypertrophy in aortic stenosis, arterial hypertension or coarctation of the aorta is risk factor for early development of HF. In chronic late compared to early left ventricular afterload increases resulting from descending thoracic оr ascending aorta stenosis, we assess the left ventricular stroke work, pressure-volume area for О2 demand and effective work on the 4th and 8th weeks. It is suggested that reduced proximal thoracic aortic compliance presents with myocardial ischemia. However, development of adverse left ventricular hypertrophic remodeling and HF in different peak of LV afterload increase is understood poorly. Methods: Fourteen domestic male pigs (28 ± 3 kg) underwent descending thoracic or ascending aortic stenosis through posterior lateral thoracotomy, with cMRI and an invasive left ventricular pressure-volume loops' аrea assessment (Millar 5Fr pig-tailed conductance catheter) on the 4th and 8th weeks. Left ventricular stroke work and pressure-volume area PVA, parameter for LV O2 demand, were assessed in hypertrophic left ventricular remodeling, resulting from different peaks in LV afterload (late vs. early LV afterload) increase and we thus defined early adverse LV hypertrophic remodeling in linear and nonlinear end-systolic pressure-volume regression analysis. For this we used special software. Data was compared with two-way repeated measures ANOVA. Results presented are means ± (SEM) or medians and significance is set at p < 0.05. Results: The left ventricular nonlinear PVA was not different, in LL compared to EL on the 8th week and when using the linear regression analysis. Stroke work was not different. The linear and nonlinear potential energy were not different between LL vs. the EL group. Nonlinear bLVO2 demand was not different, being higher in LL compared to EL in the 8th week. Indexed PVA parameters were not different or changed between the 4th and 8th weeks, when being normalized for body surface-area (m²) or 100 grams of LV mass. Conclusion: The left ventricular potential energy, PVA with effective work and LVO2 demands are not different in hypertrophic LV remodeling in LL vs. EL group at the 8th week. Difference is not present when end-systolic pressure-volume relation is assessed from indexed LV volumes for m² BSA or 100 grams of LV mass. EL is as important as LL in increased LV afterloads based on LV work and mechanical coupling in this hypertensive heart failure model having preserved EF. [ABSTRACT FROM AUTHOR]

The nasopharyngeal tube (NT) is an effective interface for noninvasive ventilation (NIV). In cases of severe heart failure, assistance with noninvasive positive-pressure ventilation (NPPV) effectively reduces afterload and alleviates respiratory effort. We present the case of a three-day-old male neonate diagnosed with severe aortic valve stenosis (AS). In respiratory management, extubation was delayed due to increased respiratory effort and afterload, so this patient was extubated and managed with NPPV using an NT. An uncuffed endotracheal tube was inserted, initiating NIV with a positive end-expiratory pressure of 8 cmH 2 O. The patient exhibited stable vital signs post-extubation and was weaned off NPPV and transferred to the general ward. In this case of severe AS, the use of NT as an interface for NPPV demonstrated efficacy in respiratory and circulatory management. This approach could have shortened the duration of mechanical ventilation and facilitated safe postoperative care, highlighting the potential benefits of NT in managing severe heart failure., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tanimura et al.)

Aims Pressure overload (PO) and volume overload (VO) lead to concentric or eccentric hypertrophy. Previously, we could show that activation of signalling cascades differ in in vivo mouse models. Activation of these signal cascades could either be induced by intrinsic load sensing or neuro-endocrine substances like catecholamines or the renin-angiotensinaldosterone system. Methods and results We therefore analysed the activation of classical cardiac signal pathways [mitogen-activated protein kinases (MAPKs) (ERK, p38, and JNK) and Akt-GSK3β] in in vitro of mechanical overload (ejecting heart model, rabbit and human isolated muscle strips). Selective elevation of preload in vitro increased AKT and GSK3β phosphorylation after 15 min in isolated rabbit muscles strips (AKT 49%, GSK3β 26%, P < 0.05) and in mouse ejecting hearts (AKT 51%, GSK49%, P < 0.05), whereas phosphorylation of MAPKs was not influenced by increased preload. Selective elevation of afterload revealed an increase in ERK phosphorylation in the ejecting heart (43%, P < 0.05), but not in AKT, GSK3β, and the other MAPKs. Elevation of preload and afterload in the ejecting heart induced a significant phosphorylation of ERK (95%, P < 0.001) and showed a moderate increased AKT (P = 0.14) and GSK3β (P = 0.21) phosphorylation, which did not reach significance. Preload and afterload elevation in muscles strips from human failing hearts showed neither AKT nor ERK phosphorylation changes. Conclusions Our data show that preload activates the AKT–GSK3β and afterload the ERK pathway in vitro, indicating an intrinsic mechanism independent of endocrine signalling. [ABSTRACT FROM AUTHOR]

Paradoxical low-flow/low-gradient aortic stenosis (P-LFLG-AS) occurs in about one-third of patients with severe AS and preserved left ventricular (LV) ejection fraction (EF). Our aim was to differentiate between altered LV loading conditions and contractility as determinants of subtle LV systolic dysfunction in P-LFLG-AS. We retrospectively analyzed medical records of patients with isolated severe degenerative AS and preserved EF (30 subjects with P-LFLG-AS and 30 patients with normal-flow/high-gradient severe AS (NFHG-AS)), without relevant coexistent diseases (e.g., diabetes, coronary artery disease and chronic kidney disease) or any abnormalities which could account for a low-flow state. Patients with P-LFLG-AS and NFHG-AS did not differ in aortic valve area index and most clinical characteristics. Compared to NFHG-AS, subjects with P-LFLG-AS exhibited smaller LV end-diastolic diameter (LVd) (44 ± 5 vs. 54 ± 5 mm, p < 0.001) (consistent with lower LV preload) with pronounced concentric remodeling, higher valvulo-arterial impedance (3.8 ± 1.1 vs. 2.2 ± 0.5 mmHg per mL/m2, p < 0.001) and diminished systemic arterial compliance (0.45 ± 0.11 vs. 0.76 ± 0.23 mL/m2 per mmHg, p < 0.001), while circumferential end-systolic LV midwall stress (cESS), an estimate of afterload at the LV level, was similar in P-LFLG-AS and NFHG-AS (175 ± 83 vs. 198 ± 69 hPa, p = 0.3). LV midwall fractional shortening (mwFS) was depressed in P-LFLG-AS vs. NFHG-AS (12.3 ± 3.5 vs. 14.7 ± 2.9%, p = 0.006) despite similar EF (61 ± 6 vs. 59 ± 8%, p = 0.4). By multiple regression, the presence of P-LFLG-AS remained a significant predictor of lower mwFS compared to NFHG-AS upon adjustment for cESS (β ± SEM: −2.35 ± 0.67, p < 0.001); however, the significance was lost after further correction for LVd (β = −1.10 ± 0.85, p = 0.21). In conclusion, the association of P-LFLG-AS with a lower cESS-adjusted mwFS, an index of afterload-corrected LV circumferential systolic function at the midwall level, appears secondary to a smaller LV end-diastolic cavity size according to the Frank–Starling law. Thus, low LV preload, not intrinsic contractile dysfunction or excessive afterload, may account for impaired LV circumferential midwall systolic performance in P-LFLG-AS. [ABSTRACT FROM AUTHOR]

Abstract Background The novel noninvasive pressure-strain loop (PSL) is a reliable tool that reflects myocardial work (MW). Systolic blood pressure (SBP) is the only independent factor for MW indices. However, afterload-related reference values have not been previously reported. The aim of the present study was to establish reference values for MW parameters by wide range SBP grading. Methods We prospectively selected healthy individuals and subjects with SBP ≥ 140 mmHg at the time of study without myocardial remodeling. MW parameters were collected and the reference values achieved were grouped by SBP in 10-mmHg. Results Significant differences were noted among the SBP-groups for global work index (GWI) and global constructive work (GCW). The majority of statistical comparisons of the differences in GWI and GCW were significant at each SBP-group. With SBP ranging from 90 to 189 mmHg, the parameters GWI and GCW tended to increase linearly with afterload. Overall, the global wasted work (GWW) tended to rise as SBP was increased, but not all of the differences noted in GWW were significant for each SBP-group. Global work efficiency (GWE) remained stable across all SBP-groups, with the exception of a slight drop noted when it exceeded 160 mmHg. Conclusions The amount of MW but not the work efficiency varied greatly according to the different afterload. This finding cannot be ignored during clinical research or diagnosis and afterload-related reference values are required to make a reasonable judgment on the myocardial function.

Keywords: afterload; pulmonary hypertension; reverse remodelling; right ventricle EN afterload pulmonary hypertension reverse remodelling right ventricle 397 399 3 02/03/23 20230201 NES 230201 The right ventricle makes a comeback Remodelling of the right ventricle (RV) is an adaptive response characterized by hypertrophy, fibrosis and stiffening in the presence of supraphysiological pulmonary vasculature afterload. Whether this truly recreates the systemic response to RV afterload, including extracardiac organ dysfunction (congestive hepatopathy, renovascular congestion and splanchnic remodelling) was not assessed and is an important consideration in appropriate models of RV dysfunction and can hopefully be verified in subsequent studies (Boehm et al., [1]). Preclinical investigations show that the extent of RV fibrosis follows an intimate relationship with the degree of RV dysfunction and the ejection fraction (EF) (Rain et al., [4]). [Extracted from the article]

Abstract Background Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis. Methods Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference. Results Sixty-seven patients were assessed (55 males), with a median age of 61 [50–70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers’ concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices. Conclusions In this comprehensive hemodynamic evaluation in critically ill COVID-19 septic patients, we identified four homogeneous and coherent clusters with a good feasibility. AMI was common and associated with alteration of LV and RV functions. Echocardiographic assessment had a clinical impact on patient management in most cases.

Treatment of D- transposition of great arteries (DTGA) involves the Arterial Switch Operation (ASO), which can create PA branch stenosis (PABS) and alter PA blood flow energetics. This altered PA flow may contribute to elevated right ventricular (RV) afterload more significantly than stenosis alone. Our aim was to correlate RV afterload and PA flow characteristics using 4D flow cardiac magnetic resonance (CMR) imaging of a mock circulatory system (MCS) incorporating 3D printed replicas. CMR imaging and clinical characteristics were analyzed from 22 ASO patients (age 11.9 ± 8.7 years, 68% male). Segmentation was performed to create 3D printed PA replicas that were mounted in an MRI-compatible MCS. Pressure drop across the PA replica was recorded and 4D flow CMR acquisitions were analyzed for blood flow inefficiency (energy loss, vorticity). In post-ASO patients, there is no difference in RV mass (p = 0.07), nor RV systolic pressure (p = 0.26) in the presence or absence of PABS. 4D flow analysis of MCS shows energy loss is correlated to RV mass (p = 0.01, r = 0.67) and MCS pressure differential (p = 0.02, r = 0.57). Receiver operating characteristic curve shows energy loss detects elevated RV mass above 30 g/m2 (p = 0.02, AUC 0.88) while index of PA dimensions (Nakata) does not (p = 0.09, AUC 0.79). PABS alone does not account for differences in RV mass or afterload in post-ASO patients. In MCS simulations, energy loss is correlated with both RV mass and PA pressure, and can moderately detect elevated RV mass. Inefficient PA flow may be an important predictor of RV afterload in this population. [ABSTRACT FROM AUTHOR]