Ventricular Pressure-volume Loops Research Articles

No Difference in Systolic Dysfunction from Left Ventricular Pressure-Volume Loop’s Area and Stroke Work Between Chronic Late Load vs. Early Systolic LV Load in Porcine Model

<i>Background: </i>in increased LV afterload as in hypertension, early systolic LV dysfunction (SD) in late compares to early peak systolic LV load for P-V area, stroke work, potential energy with effective LV work (EW) is not being defined (aortic stenosis, arterial hypertension or coarctation of the aorta) in LVH remodeling. <i>Objectives:</i> to assess in porcine model how LV stroke work, PVA and EW are related to LVH remodeling in developing early SD with HF, between 4<sup>th</sup> vs 8<sup>th</sup> week in chronic LL compares to EL. It is suggested that reduced proximal thoracic or asc. aortic compliance results with myocardial ischemia. However, difference for LV O<sub>2</sub> demand and effective LV work in different LV afterload is not understood in early development systolic HF. <i>Methods:</i> in fourteen domestic male pigs (28±3 kg) with moderate descending aortic banding having chronic late LV load (LL=8) or ascending aortic stenosis with early systolic LV load (EL=6) SD was assessed, from PVA, in invasive LV pressure-volume loops’ measurements, at 4<sup>th</sup> vs. 8<sup>th</sup> week, to assess LV maximal ESPVR, with Millar 5Fr P-V pig-tailed conductance catheter. LV stroke work, and pressure-volume area PVA, reflecting the maximal LV O<sub>2</sub> demand were assessed in chronic LL compares to EL from nonlinear regression analysis of maximal LV end-systolic stiffness, in special software. For variance analysis, two-way repeated measures ANOVA was performed, with normality assessment. Results are means±(SEM) or medians for significant p<0.05. <i>Results: </i>LV PVA was not different, in LL compared to EL at 4<sup>th</sup> vs. 8<sup>th</sup> week. LV stroke work with effective works were not different and potential energy, neither were changed between 4<sup>th</sup> vs. 8<sup>th</sup> week. No difference was found in different LV afterload, in both indexed and absolute LVO<sub>2</sub> demand, in LL vs. EL at 4<sup>th</sup> or 8<sup>th</sup> week. Indexed PVA parameters with LV stroke work, effective work and potential energy were not different or changed in LL compares to EL between 4<sup>th</sup> vs. 8<sup>th</sup> weeks, normalized per body surface-area (in m<sup>2</sup>). <i>Conclusion:</i> Both absolute and indexed LV stroke work, potential LV energy, PVA with EW and maximum LV O<sub>2</sub> demand are not different in LL compares to EL at 4<sup>th</sup> vs. 8<sup>th</sup> week of LVH remodeling, indicating no difference in early SD development in increased late vs. early LV afterload.

Diagnosing heart failure with preserved ejection fraction in patients with unexplained dyspnoea using left ventricular pressure-volume loops at rest and on exertion

Abstract Background To date, diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, especially in euvolaemic patients presenting with unexplained dyspnoea on exertion and reduced exercise capacity. A stepwise approach was introduced with the HFA-PEFF diagnostic algorithm*, in which a relevant number of patients has to undergo invasive workup for a final judgement. Purpose The present study aimed to examine a population of patients with unexplained dyspnoea on exertion, using the diagnostic methods endorsed by the HFA-PEFF algorithm as well as left ventricular (LV) pressure-volume loops at rest, on exertion, and during caval occlusion, in order to identify and describe different phenotypes of HFpEF. Methods We prospectively included patients with unexplained dyspnoea on exertion, a left ventricular ejection fraction (LVEF) of ≥ 50%, and without an obvious cause of the dyspnoea. All patients underwent a comprehensive invasive haemodynamic workup. After invasive rule-out of a haemodynamically relevant coronary artery stenosis, we performed a right heart catheterization at rest (R) and on exertion (E) with an arm ergometer. Real-time continuous pressure-volume loops were obtained using a 7-French conductance catheter at rest, on exertion, and under temporal preload reduction via partial occlusion of the vena cava inferior. Results Thirty patients were included. Two patients had to be excluded from further analysis (one due to a technical failure of the conductance catheter and one with severe hypertension (systolic blood pressure > 200 mmHg) during the assessment). The 28 patients in this analysis had a mean age of 64.4±9.7 years and 57% were female. Eleven patients fulfilled invasively easily obtainable diagnostic criteria of HFpEF (mean pulmonary capillary wedge pressure (mPCWP) at rest ≥ 15 mmHg, exertional mPCWP ≥ 25 mmHg, LV end-diastolic pressure (LVEDP) at rest ≥ 16 mmHg, or exertional LVEDP ≥ 25 mmHg) according to the current guideline*. An additional 15 patients had a normal mPCWP and LVEDP, but fulfilled diagnostic criteria for HFpEF measured by the conductance catheter (time constant of LV relaxation tau > 48 ms and/ or chamber stiffness b > 0.27). We referred to this group as "early HFpEF". Patients with early HFpEF had a significantly higher systolic blood pressure, a worse LV relaxation time, and were more likely to exhibit chronotropic insufficiency compared to the HFpEF group (Table 1). HFpEF patients were characterised by significantly higher natriuretic peptides, LVEDP on exertion, and LV stiffness compared to patients with early HFpEF (pressure-volume loops are depicted in Figure 1). Conclusion Invasive haemodynamic testing for HFpEF in patients with unexplained dyspnoea on exertion via right heart catheterization without obtaining LV pressure-volume loops had a false negative rate of 58%. Better detection, the prognosis, and treatment of this "early HFpEF" population warrants further research.Table 1Figure 1

Deep phenotyping of unaffected carriers of pathogenic BMPR2 variants screened for pulmonary arterial hypertension.

Pathogenic variants in the gene encoding for BMPR2 are a major genetic risk factor for heritable pulmonary arterial hypertension. Owing to incomplete penetrance, deep phenotyping of unaffected carriers of a pathogenic BMPR2 variant through multimodality screening may aid in early diagnosis and identify susceptibility traits for future development of pulmonary arterial hypertension. 28 unaffected carriers (44±16 years, 57% female) and 21 healthy controls (44±18 years, 48% female) underwent annual screening, including cardiac magnetic resonance imaging, transthoracic echocardiography, cardiopulmonary exercise testing and right heart catheterisation. Right ventricular pressure-volume loops were constructed to assess load-independent contractility and compared with a healthy control group. A transgenic Bmpr2Δ71Ex1/+ rat model was employed to validate findings from humans. Unaffected carriers had lower indexed right ventricular end-diastolic (79.5±17.6 mL·m-2 versus 62.7±15.3 mL·m-2; p=0.001), end-systolic (34.2±10.5 mL·m-2 versus 27.1±8.3 mL·m-2; p=0.014) and left ventricular end-diastolic (68.9±14.1 mL·m-2 versus 58.5±10.7 mL·m-2; p=0.007) volumes than control subjects. Bmpr2Δ71Ex1/+ rats were also observed to have smaller cardiac volumes than wild-type rats. Pressure-volume loop analysis showed that unaffected carriers had significantly higher afterload (arterial elastance 0.15±0.06 versus 0.27±0.08 mmHg·mL-1; p<0.001) and end-systolic elastance (0.28±0.07 versus 0.35±0.10 mmHg·mL-1; p=0.047) in addition to lower right ventricular pulmonary artery coupling (end-systolic elastance/arterial elastance 2.24±1.03 versus 1.36±0.37; p=0.006). During the 4-year follow-up period, two unaffected carriers developed pulmonary arterial hypertension, with normal N-terminal pro-brain natriuretic peptide and transthoracic echocardiography indices at diagnosis. Unaffected BMPR2 mutation carriers have an altered cardiac phenotype mimicked in Bmpr2Δ71Ex1/+ transgenic rats. Future efforts to establish an effective screening protocol for individuals at risk for developing pulmonary arterial hypertension warrant longer follow-up periods.

Active decompression during automated head-up cardiopulmonary resuscitation

BackgroundThe combination of active compression-decompression cardiopulmonary resuscitation (ACD-CPR) with an impedance threshold device (ITD) and controlled head-up positioning (AHUP-CPR) is associated with improved outcomes compared with conventional CPR (C-CPR). This study focused on the role of active decompression (AD) during AHUP-CPR. MethodsFarm pigs (n = 10, ∼40 kg) were anesthetized, intubated and ventilated. Physiological parameters and right ventricular pressure–volume loops were recorded continuously. Ventricular fibrillation was induced and left untreated for 10 mins, followed by automated C-CPR (2 min), ACD + ITD CPR in the flat position (2 min), and then AHUP-CPR with 3 cm of lift above the neutral chest position. After 15 min of CPR, AD was discontinued and then restarted incrementally to 4 cm. Data were analyzed with a linear mixed-effects model, using random intercepts for individual pigs. ResultsUpon cessation of AD during AHUP-CPR, decompression right atrial pressure (+59%) increased (p < 0.01), whereas multiple hemodynamic parameters positively associated with perfusion, including coronary (−25%) and cerebral perfusion pressures (−11%), end-tidal CO2 (−13%), stroke volume and cardiac output (−26%), decreased immediately and significantly with p < 0.05. Restoration of AD reduced right atrial pressure and increased positive perfusion parameters in an incremental manner. Only with ≥ 3 cm of AD were all hemodynamic parameters restored to ≥ 90% of pre-AD discontinuation levels. ConclusionFull chest wall lift, achieved with ≥ 3 cm of AD, was needed to maintain and optimize hemodynamics during AHUP-CPR in pigs. These findings should be considered when optimizing care with this new approach.

LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.

Conduit pulmonary arterial stiffening and the resultant increase in pulmonary vascular impedance have emerged as an important underlying driver of pulmonary arterial hypertension (PAH). Given that matrix deposition is central to vascular remodeling, we evaluated the role of the collagen cross-linking enzyme lysyl oxidase like 2 (LOXL2) in this study. Human pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia showed increased LOXL2 secretion. LOXL2 activity and expression were markedly higher in primary PASMCs isolated from the pulmonary arteries of the rat Sugen 5416 + hypoxia (SuHx) model of severe pulmonary hypertension (PH). Similarly, LOXL2 protein and mRNA levels were increased in the pulmonary arteries (PA) and lungs of rats with PH (SuHx and monocrotaline (MCT) models). Pulmonary arteries (PAs) isolated from the rats with PH exhibited hypercontractility to phenylephrine and attenuated vasorelaxation elicited by acetylcholine, indicating severe endothelial dysfunction. Tensile testing revealed a significant increase in PA stiffness in PH. Treatment with PAT-1251, a novel small-molecule LOXL2 inhibitor, improved active and passive properties of the PA ex vivo. There was an improvement in right heart function as measured by right ventricular pressure volume loops in vivo with PAT-1251. Importantly, PAT-1251 treatment ameliorated PH, resulting in improved pulmonary artery pressures, right ventricular remodeling, and survival. Hypoxia-induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH and pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 could be a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH.NEW & NOTEWORTHY Pulmonary arterial stiffening contributes to the progression of PAH and the deterioration of right heart function. This study shows that LOXL2 is upregulated in rat models of PH. LOXL2 inhibition halts pulmonary vascular remodeling and improves PA contractility, endothelial function, and PA pressure, resulting in prolonged survival. Thus, LOXL2 is an important mediator of PA remodeling and stiffening in PH and a promising target to improve PA pressures and survival in PH.

Tailoring the Best Positive End-Expiratory Pressure Through Invasive Right Ventricular Pressure-Volume Loops in a Patient Supported by Veno-Arterial Extracorporeal Membrane Oxygenation.

Patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) typically suffer from cardiogenic pulmonary edema and lung atelectasis, which can exacerbate right ventricular (RV) dysfunction through an increase in lung elastance and RV afterload. Invasive mechanical ventilation settings, and positive end-expiratory pressure (PEEP) in particular, can help to improve RV performance by optimizing lung recruitment and minimizing alveolar overdistention. In this report, we present a VA-ECMO supported patient in whom in vivo RV pressure-volume (PV) loops were measured during a decremental PEEP trial, leading to the identification of an optimum PEEP level from a cardio-respiratory viewpoint. This innovative approach of tailoring mechanical ventilation settings according to cardio-respiratory physiology through in vivo RV PV loops may provide a novel way to optimize hemodynamics and patient outcomes.

Noninvasive Pressure-Volume Loops Predict Major Adverse Cardiac Events in Heart Failure With Reduced Ejection Fraction

BackgroundHeart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV) loop analysis can be performed noninvasively using cardiovascular magnetic resonance (CMR) imaging to assess cardiac thermodynamic efficiency. ObjectivesThe aim of the study was to investigate whether noninvasive PV loop parameters, derived from CMR, could predict major adverse cardiac events (MACE) in HFrEF patients. MethodsPV loop parameters (stroke work, ventricular efficiency, external power, contractility, and energy per ejected volume) were computed from CMR cine images and brachial blood pressure. The primary endpoint was MACE (cardiovascular death, heart failure (HF) hospitalization, myocardial infarction, revascularization, ventricular tachycardia/fibrillation, heart transplantation, or left ventricular assist device implantation within 5 years). Associations between PV loop parameters and MACE were evaluated using multivariable Cox regression. ResultsA total of 164 HFrEF patients (left ventricular ejection fraction ≤40%, age 63 [IQR: 55-70] years, 79% male) who underwent clinical CMR examination between 2004 and 2014 were included. Eighty-eight patients (54%) experienced at least 1 MACE after an average of 2.8 years. Unadjusted models demonstrated a significant association between MACE and all PV loop parameters (P < 0.05 for all), HF etiology (P < 0.001), left ventricular ejection fraction (P = 0.003), global longitudinal strain (P < 0.001), and N-terminal prohormone of brain natriuretic peptide level (P = 0.001). In the multivariable Cox regression analysis adjusted for age, sex, hypertension, diabetes, and HF etiology, ventricular efficiency was associated with MACE (HR: 1.04, 95% CI: 1.01-1.08, per-% decrease, P = 0.01). ConclusionsVentricular efficiency, derived from noninvasive PV loop analysis from standard CMR scans, is associated with MACE in patients with HFrEF.

LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension

Background: Conduit pulmonary arterial stiffening and the resultant increase in pulmonary vascular impedance has emerged as an important underlying driver of pulmonary arterial hypertension (PAH). Given that matrix deposition is central to vascular remodeling, we evaluated the role of the collagen crosslinking enzyme lysyl oxidase like 2 (LOXL2) in this study. Methods and Results: Human pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia showed increased LOXL2 secretion. LOXL2 activity and expression were markedly higher in primary PASMCs isolated from pulmonary arteries of the rat Sugen 5416 + hypoxia (SuHx) model of severe PH. Similarly, LOXL2 protein and mRNA levels were increased in pulmonary arteries (PA) and lungs of rats with PH (SuHx and monocrotaline (MCT) models). Pulmonary arteries (PAs) isolated from rats with PH exhibited hypercontractility to phenylephrine and attenuated vasorelaxation elicited by acetylcholine, indicating severe endothelial dysfunction. Tensile testing revealed a a significant increase in PA stiffness in PH. Treatment with PAT-1251, a novel small-molecule LOXL2 inhibitor, improved active and passive properties of the PA ex vivo. There was an improvement in right heart function as measured by right ventricular pressure volume loops in-vivo with PAT-1251. Importantly PAT-1251 treatment ameliorated PH, resulting in improved pulmonary artery pressures, right ventricular remodeling, and survival. Conclusion: Hypoxia induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH, as well as pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 is a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH. This work was supported by a NHLBI grant R01HL105296 (to D.E.B.), a NHLBI grant R01HL148112 01 (to L.S.), two Stimulating and Advancing ACCM Research (StAAR) grants from the Department of Anesthesiology and Critical Care Medicine, JHU (to L.S. and J.S.), NHLBI grants R01HL073859 and R01HL126514 (to L.A.S) and a NHLBI K08 grant K08HL145132 (to J.S.). 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.

No sex differences in the cardiac responses during high altitude sojourn to 4300 m

Ascent to high altitude reduces oxygen availability and provokes compensatory cardiovascular responses. Females may exhibit attenuated hypoxic ventilatory responses compared to males, which could subsequently exaggerate the cardiovascular response to high altitude among females. The purpose of this study was to examine sex differences in cardiac responses during high altitude sojourn in young, healthy males and females. We hypothesized that females would exhibit a greater reduction in arterial oxygen saturation, and greater cardiac dysfunction compared to males. 17 healthy adults (8 males, 24±4 yrs, BMI 25.7±3.1 kg/m2; 9 females, 23±4 yrs, BMI 24.5±3.0 kg/m2) underwent cardiac assessment via echocardiography at 1400 m and after an 8-day ascent to 4300 m. Left ventricular (LV) systolic function was assessed via ejection fraction and fractional shortening. Diastolic function was assessed as the ratio between early and late mitral filling velocities (E:A ratio). The subendocardial viability ratio (SEVR) was derived from carotid tonometry, and carotid pressure waves were integrated with echocardiography derived measures of left ventricular ejection to estimate a left ventricular pressure-volume loop and calculate stroke work. Ascent from 1400 m to 4300 m resulted in reduced end-tidal CO2 (-Δ8±3 [males], -Δ8±2 mmHg [females], p&lt;0.001), oxygen saturation (-Δ11±3 [males], -Δ11±5 % [females], p&lt;0.001), and LV fractional shortening (-Δ7.9±7.5% [males] -Δ1.0±6.4 % [females], p=0.028) in both groups. Despite greater stroke work among males (p=0.002), high altitude-induced changes were not statistically different compared to females (+Δ35±184 [males], +Δ3±113 mL/mmHg [females]). Changes in LV ejection fraction (-Δ1.9±14.4 [males], -Δ1.5±18.7 % [females]) mitral E:A (-Δ0.33±0.53 [males], -Δ0.09±0.64 au [females]), and SEVR (-Δ0.06±0.33 [males], +Δ0.15±0.20 au [females]) from 1400 to 4300 m were not statistically different between sexes. Ascent from 1400 to 4300 m decreased end-tidal CO2, arterial oxygen saturation, and select metrics of LV systolic function (e.g., fractional shortening), but LV diastolic function, stroke work, and SEVR was preserved in both males and females. We observed no apparent sex differences in the effects of 8-day sojourn to 4300 m on arterial oxygen saturation, or cardiac systolic and diastolic function. Additional research is necessary to confirm these results in the context of longer-term altitude exposure and acclimatization, and in older populations (middle-aged and older adults). 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.

Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury.

Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through in vivo and in vitro studies. Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.

Contractility, ventriculoarterial coupling, and stroke work after acute myocardial infarction using CMR-derived pressure-volume loop data.

Noninvasive left ventricular (LV) pressure-volume (PV) loops derived by cardiac magnetic resonance (CMR) have recently been shown to enable characterization of cardiac hemodynamics. Thus, such PV loops could potentially provide additional diagnostic information such as contractility, arterial elastance (Ea ) and stroke work (SW) currently not available in clinical routine. This study sought to investigate to what extent PV-loop variables derived with a novel noninvasive method can provide incremental physiological information over cardiac dimensions and blood pressure in patients with acute myocardial infarction (MI). A total of 100 patients with acute MI and 75 controls were included in the study. All patients underwent CMR 2-6 days after MI including assessment of myocardium at risk (MaR) and infarct size (IS). Noninvasive PV loops were generated from CMR derived LV volumes and brachial blood pressure measurements. The following variables were quantified: Maximal elastance (Emax ) reflecting contractility, Ea , ventriculoarterial coupling (Ea /Emax ), SW, potential energy, external power, energy per ejected volume, and efficiency. All PV-loop variables were significantly different in MI patients compared to healthy volunteers, including contractility (Emax : 1.34 ± 0.48 versus 1.50 ± 0.41 mmHg/mL, p = .024), ventriculoarterial coupling (Ea /Emax : 1.27 ± 0.61 versus 0.73 ± 0.17, p < .001) and SW (0.96 ± 0.32 versus 1.38 ± 0.32 J, p < .001). These variables correlated to both MaR and IS (Emax : r2 = 0.25 and r2 = 0.29; Ea /Emax : r2 = 0.36 and r2 = 0.41; SW: r2 = 0.21 and r2 = 0.25). Noninvasive PV-loops provide physiological information beyond conventional diagnostic variables, such as ejection fraction, early after MI, including measures of contractility, ventriculoarterial coupling, and SW.

Kiosk 10R-FB-05 - Noninvasive Left Ventricular Pressure-volume Loops Derived FBom 4D Flow CMR and CFD

Kiosk 10R-FB-05 - Noninvasive Left Ventricular Pressure-volume Loops Derived FBom 4D Flow CMR and CFD

Non-invasive pressure-volume loops from cardiovascular magnetic resonance predict cardiovascular mortality in heart failure with reduced ejection fraction

Abstract Background Heart failure with reduced ejection fraction (HFrEF) is characterized by impaired ventricular energetics secondary to ventricular remodeling. Left ventricular pressure-volume (PV) loop analysis (Figure 1) can now be performed noninvasively using cardiovascular magnetic resonance (CMR) imaging, enabling study of cardiac thermodynamic efficiency without the risk and cost associated with invasive measurements (1–3). Here we investigated whether noninvasive PV loops from CMR can predict cardiovascular death in HFrEF patients. Methods We analyzed 135 datasets (age 60±12 years, 79% male) from HFrEF patients (LVEF≤40%) who underwent clinical CMR examination at our center between 2004-2013. Pressure-volume loop parameters were computed from manually segmented CMR data and same-day brachial blood pressure (Segment 4.0 R11026, Medviso, Lund, Sweden). The primary endpoint was cardiovascular mortality extracted from national registries with a 5-year follow-up. Parameters of interest were selected from univariate Cox regression, and associations with clinical outcome evaluated using multivariate Cox regression. Survival was visualized using Kaplan-Meier analysis. Statistical analysis was performed in R 4.0.3 (R Core Team). Results A total of 19 deaths from cardiovascular causes occurred during follow-up. Univariate Cox regression found stroke work (SW, joule), ventricular efficiency (VE, %), external power (J/s), contractility (mmHg/ml), and energy per ejected volume (mJ/ml) computed from PV loops associated with the primary endpoint alongside age, LVEF, and NT-proBNP level. In multivariate Cox regression adjusted for age, ventricular efficiency remained significant (HR 0.86, p&amp;lt;0.001), while EF did not (p = 0.077). Event-free survival is shown in Figure 2. Conclusion Ventricular efficiency derived from non-invasive pressure-volume loop analysis from standard CMR scans, may outperform LV EF as a predictor of cardiovascular mortality in HFrEF. Figures: Figure 1. Example of left ventricular pressure-volume (PV) loop. The area enclosed by the loop is the stroke work (SW). The area bounded by the PV loop and the end-systolic pressure-volume relationship (ESPVR) is the potential energy (PE). Ventricular efficiency (VE) is calculated as SW/(PE+SW). Figure 2. Kaplan-Meier plots of survival by tertiles of stroke work and ventricular efficiency.Figure 1Figure 2

Heart failure classifications via non-invasive pressure volume loops from echocardiography.

Left ventricular pressure-volume (LV-PV) loops provide comprehensive characterization of cardiovascular system in both health and disease, which are the essential element of the hemodynamic evaluation of heart failure (HF). This study attempts to achieve more detailed HF classifications by non-invasive LV-PV loops from echocardiography and analyzes contribution of parameters to HF classifications. Firstly, non-invasive PV loops are established by time-varying elastance model where LV volume curves were extracted from apical-four-chambers view of echocardiographic videos. Then, 16 parameters related to cardiac structure and functions are automatically acquired from PV loops. Next, we applied six machine learning (ML) methods to divide four categories. On this premise, we choose the best performing classifier among machine learning approaches for feature ranking. Finally, we compare the contributions of different parameters to HF classifications. By the experimental, the PV loops were successfully acquired in 1076 cases. When single left ventricular ejection fraction (LVEF) is used for HF classifications, the accuracy of the model is 91.67%. When added parameters extracted from ML-derived LV-PV loops, the classification accuracy is 96.57%, which improved by 5.1%. Especially, our parameters have a great improvement in the classification of non-HF controls and heart failure with preserved ejection fraction (HFpEF). We successfully presented the classification of HF by machine derived non-invasive LV-PV loops, which has the potential to improve the diagnosis and management of heart failure in clinic. Moreover, ventriculo-arterial (VA) coupling and ventricular efficiency were demonstrated important factors for ML-based HF classification model besides LVEF.

The hemodynamic interplay between pulmonary ischemia-reperfusion injury and right ventricular function in lung transplantation: A translational porcine model.

Lung transplantation is a challenging procedure. Following the process of ischemia-reperfusion injury, the transplanted pulmonary graft might become severely damaged, resulting in primary graft dysfunction. Additionally, during the intra-operative window, the right ventricle is at risk of acute failure. The interaction of right ventricular function with lung injury, is however, poorly understood. We aimed to address this interaction in a translational porcine model of pulmonary ischemia-reperfusion injury. Advanced pulmonary and hemodynamic assessment was used, including right ventricular pressure-volume loop analysis. The acute model was based on clamping and unclamping of the left lung hilus, respecting the different hemodynamic phases of a clinical lung transplantation. We found that forcing entire right ventricular cardiac output through a lung suffering from ischemia-reperfusion injury increased afterload (pulmonary vascular resistance from baseline to end experiment p <0.0001) and induced right ventricular failure in 5/9 animals. Notably, we identified different compensation patterns in failing versus non-failing ventricles (arterial elastance p=0.0008; stroke volume p <0.0001). Furthermore, increased vascular pressure and flow produced by the right ventricle resulted in higher pulmonary injury, as measured by ex-vivo CT density (correlation: pressure r=0.8; flow r= 0.85). Finally, RV ischemia as measured by troponin-T was negatively correlated with pulmonary injury (r=-0.76), however, troponin-T values did not determine RVF in all animals. In conclusion, we demonstrate a delicate balance between development of pulmonary ischemia-reperfusion injury and right ventricular function during lung transplantation. Furthermore, we provide a physiological basis for potential benefit of extracorporeal life support technology.

Non-invasive left ventricular pressure-volume loops from cardiovascular magnetic resonance imaging and brachial blood pressure: validation using pressure catheter measurements.

Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. A non-invasive method for the computation of PV loops from magnetic resonance imaging and brachial cuff blood pressure has recently been proposed. Here we evaluated the fidelity of the non-invasive PV algorithm against invasive LV pressures in humans. Four heart failure patients with EF < 35% and LV dyssynchrony underwent cardiovascular magnetic resonance (CMR) imaging and subsequent LV catheterization with sequential administration of two different intravenous metabolic substrate infusions (insulin/dextrose and lipid emulsion), producing eight datasets at different haemodynamic states. Pressure-volume loops were computed from CMR volumes combined with (i) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, or (ii) invasive pressures averaged from 19 to 30 sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis. Non-invasively derived PV loop parameters demonstrated high correlation and low bias when compared to invasive data for stroke work (R2 = 0.96, P < 0.0001, bias 4.6%), potential energy (R2 = 0.83, P = 0.001, bias 1.5%), end-systolic pressure-volume relationship (R2 = 0.89, P = 0.0004, bias 5.8%), ventricular efficiency (R2 = 0.98, P < 0.0001, bias 0.8%), arterial elastance (R2 = 0.88, P = 0.0006, bias -8.0%), mean external power (R2 = 0.92, P = 0.0002, bias 4.4%), and energy per ejected volume (R2 = 0.89, P = 0.0001, bias 3.7%). Variations in estimated end-diastolic pressure did not significantly affect results (P > 0.05 for all). Intraobserver analysis after one year demonstrated 0.9-3.4% bias for LV volumetry and 0.2-5.4% for PV loop-derived parameters. Pressure-volume loops can be precisely and accurately computed from CMR imaging and brachial cuff blood pressure in humans.

Echocardiographic pressure-strain loop-derived stroke work of the right ventricle: validation against the gold standard.

Commercially available integrated software for echocardiographic measurement of stroke work (SW) is increasingly used for the right ventricle, despite a lack of validation. We sought to assess the validity of this method [echo-based myocardial work (MW) module] vs. gold-standard invasive right ventricular (RV) pressure-volume (PV) loops. From the prospectively recruiting EXERTION study (NCT04663217), we included 42 patients [34 patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) and 8 patients with absence of cardiopulmonary disease] with RV echocardiography and invasive PV catheterization. Echocardiographic SW was assessed as RV global work index (RVGWI) generated via the integrated pressure-strain MW software. Invasive SW was calculated as the area bounded by the PV loop. An additional parameter derived from the MW module, RV global wasted work (RVGWW), was correlated with PV loop measures. RVGWI significantly correlated with invasive PV loop-derived RV SW in the overall cohort [rho=0.546 (P<0.001)] and the PAH/CTEPH subgroup [rho=0.568 (P<0.001)]. Overall, RVGWW correlated with invasive measures of arterial elastance (Ea), the ratio of end-systolic elastance (Ees)/Ea, and end-diastolic elastance (Eed) significantly. Integrated echo measurement of pressure-strain loop-derived SW correlates with PV loop-based assessment of RV SW. Wasted work correlates with invasive measures of load-independent RV function. Given the methodological and anatomical challenges of RV work assessment, evolution of this approach by incorporating more elaborated echo analysis data and an RV reference curve might improve its reliability to mirror invasively assessed RV SW.

Clinical Applications of Pressure-Volume Assessment in Congenital Heart Disease.

Ventricular pressure-volume (PV) loops offer unique insights into cardiovascular mechanics. PV loops can be instrumental in improving our understanding of various congenital heart diseases, including single ventricular physiology, heart failure, and pulmonary hypertension, as well as guiding therapeutic interventions. This review focuses on the theoretical and practical foundations for the acquisition and interpretation of PV loops in congenital heart disease and discusses their clinical applications.

Class of hemorrhagic shock is associated with progressive diastolic coronary flow reversal and diminished left ventricular function.

Introduction: The relationship between coronary artery flow and left ventricular (LV) function during hemorrhagic shock remains unknown. The aim of this study was to quantify coronary artery flow directionality alongside left ventricular function through the four classes of hemorrhage shock. Methods: Following baseline data collection, swine were exsanguinated into cardiac arrest via the femoral artery using a logarithmic bleed, taking each animal through the four classes of hemorrhagic shock based on percent bleed (class I: 15%; class II: 15%-30%; class III: 30%-40%; class IV: >40%). Telemetry data, left ventricular pressure-volume loops, and left anterior descending artery flow tracings over numerous cardiac cycles were collected and analyzed for each animal throughout. Results: Five male swine (mean 72 ± 12kg) were successfully exsanguinated into cardiac arrest. Mean left ventricular end-diastolic volume, end-diastolic pressure, and stroke work decreased as the hemorrhagic shock class progressed (p < 0.001). The proportion of diastole spent with retrograde coronary flow was also associated with class of hemorrhagic shock (mean 5.6% of diastole in baseline, to 63.9% of diastole in class IV; p < 0.0001), worsening at each class from baseline through class IV. Preload recruitable stroke work (PRSW) decreased significantly in classes II through IV (p < 0.001). Systemic Vascular Resistance (SVR) is associated with class of hemorrhage shock (p < 0.001). Conclusion: With progressive classes of hemorrhagic shock left ventricular function progressively decreased, and the coronary arteries spent a greater proportion of diastole in retrograde flow, with progressively more negative total coronary flow. Preload recruitable stroke work, a load-independent measure of inotropy, also worsened in severe hemorrhagic shock, indicating the mechanism extends beyond the drop in preload and afterload alone.

Invasive validation of pressure-volume loops derived from cardiovascular magnetic resonance imaging and brachial blood pressure in heart failure patients

Abstract Introduction Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. Recent development has seen the introduction of non-invasively computed PV loops from cardiovascular magnetic resonance (CMR) volumetry and a brachial blood pressure measurement. The approach combines LV volumes with a time-varying elastance function to compute time-resolved LV pressures and was validated on invasive pressure data from a porcine model. The method is readily implemented using standard CMR sequences and provides measures of hemodynamic parameters including stroke work, myocardial efficiency, and contractile state. However, the method remains to be validated in patients using invasive left ventricular pressure recordings. Purpose To validate for the first time in human patients the performance of non-invasively computed PV loops against invasive measures. Methods Four heart failure patients underwent two subsequent sessions of CMR cine imaging and simultaneous brachial blood pressure measurement, with intravenous administration of two different vasoactive drugs, resulting in two different haemodynamic states for each patient. LV catheterization was then conducted with repeat administration of the same infusions. Pressure-volume loops were computed from CMR volumes combined with 1) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, and 2) invasive pressures averaged from multiple sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis. Results Figure 1 shows non-invasively derived PV loop parameters compared to invasive data. The non-invasive method demonstrated strong correlations and low bias for stroke work (R2=0.97, bias 4.6%, p&amp;lt;0.0001), potential energy (R2=0.83, bias 1.5%, p=0.001), end-systolic pressure-volume relationship (R2=0.90, bias 5.4%, p=0.0003), energy per ejected volume (R2=0.93, bias 3.5%, p=0.0001), ventricular efficiency (R2=0.99, bias 1.1%, p&amp;lt;0.0001), arterial elastance (R2=0.87, bias −7.8%, p=0.0006), and mean external power (R2=0.89, bias 4.6%, p=0.0005). Conclusions Pressure-volume loops can be precisely and accurately computed from cardiovascular magnetic resonance imaging and brachial cuff blood pressure in humans, and is ready for use in research applications. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung Foundation