Angiotensin receptor-neprilysin inhibition and improved ventricular-arterial coupling in heart failure with reduced ejection fraction.

Sacubitril/valsartan improves outcome in chronic heart failure (HF) with reduced ejection fraction (EF). The underlying mechanisms on left ventricular (LV) myocardial function are incompletely understood. In this study, 117 patients with symptomatic HF and LV-EF ≤ 40% were enrolled prospectively. Non-invasive pressure-volume analysis was calculated from transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements. Primary outcome parameters were LV end-systolic elastance (Ees; a measure of LV contractility), effective arterial elastance (Ea; a measure of afterload), and the ventricular-arterial coupling ratio (Ea/Ees). Mean age was 65±13 years, 30% were female, and 54.7% had ischemic heart disease. During six months of follow-up, eight patients died, three withdrew their consent, and four were lost to follow-up. 102 patients were included in pressure-volume analyses. After six months of sacubitril/valsartan treatment, Ees increased (0.66mmHg/ml [IQR 0.45-0.94] vs. 0.78mmHg/ml [IQR 0.57-1.10], p=0.001), Ea decreased (1.76mmHg/ml [IQR 1.48-2.13] vs. 1.62mmHg/ml [IQR 1.36-1.96], p=0.014), and the Ea/Ees ratio improved (2.52 [IQR 1.88-4.05] vs. 1.93 [IQR 1.50-2.63], p<0.001). LV end-diastolic pressure and LV volumes were reduced, and LVEF increased from 33% to 43% (both p<0.001). Clinical improvement occurred in NYHA functional class, NT-proBNP level, and 6-minute walking distance. Change in LVEF correlated with change in Ees (r=0.33, p=0.0008), while change in NT-proBNP was associated with change in LVEDP (r=0.42, p<0.0001). In conclusion, sacubitril/valsartan is associated with improved ventricular-arterial coupling by enhancing LV contractility and reducing afterload. Beyond LV reverse remodeling, optimized ventricular-arterial interaction may contribute to the favorable outcome of sacubitril/valsartan treatment in HF with reduced EF.

Volume Calibration with Cardiac MRI vs Hypertonic Saline for Right Ventricular Pressure-Volume Loops with Exercise: Impact on ventricular function and ventricular-vascular coupling.

Right ventricular (RV) pressure-volume (PV) loops require post-acquisition volume calibration by cardiac MRI (CMR) or hypertonic saline (HS). We defined the impact of these two volume calibration methods on rest-to-exercise ventricular contractility (end-systolic elastance: Ees), arterial afterload (Ea) and coupling (Ees/Ea). In a prospective study, 82 RV PV-loop datapoints (rest, exercise stages-every 25watts and recovery) and CMR were acquired in 19 participants. In comparison to CMR, HS-based calibration over-estimated RV end-systolic volume at rest, mean (SD) by +38 mL (48) and end-diastolic volume by +46 mL (68), resulting in underestimated RVEF by -8%. However, Ees and Ea were similar at rest (r2=0.76 and 0.71 respectively, p<0.001 for both) and Ees:Ea was identical (r2=1.00, p<0.001). Exercise metrics also remained similar: RV reserve (ΔEes) and change in coupling (ΔEes/Ea). In comparison to CMR (gold-standard), HS-based calibration under-estimates RVEF at rest, however it is a robust approach for measuring coupling and RV reserve.

Higher Flower Hydraulic Safety, Drought Tolerance and Structural Resource Allocation Provide Drought Adaptation to Low Mean Annual Precipitation in Caragana Species.

Determining the differences in flower hydraulic traits and structural resource allocation among closely related species adapted to low mean annual precipitation (MAP) can provide insight into plant adaptation to arid environments. Here, we measured the maximum flower hydraulic conductance (Kmax-flower), water potential at induction 50% loss of Kmax-flower (P50-flower), flower pressure-volume parameters, dry mass of individual flowers and structural components (vexillum, wings, keels, stamens and sepals) of six Caragana species growing in regions ranging from 110 to 1400 mm MAP. Compared with species from high-MAP environments, those from low-MAP environments presented lower Kmax-flower, more negative P50-flower, osmotic potential at full turgor (πo) and turgor loss points (πtlp), and a greater bulk modulus of elasticity (ε). Consequently, a negative correlation between Kmax-flower (hydraulic efficiency) and P50-flower (hydraulic safety) was observed across Caragana species. Furthermore, the dry masses of individual flowers and structural components (vexillum, wings, keels, stamens and sepals) were greater in the species from the low-MAP environment than in those from the high-MAP environment. These findings suggest that greater flower hydraulic safety and drought tolerance combined with greater structural resource allocation promote drought adaptation in Caragana species to low-MAP environments.

Atrial septal defect closure in children at young age is beneficial for left ventricular function.

Aims: Atrial septal defects (ASDs) lead to volume-loaded right ventricles (RVs). ASD closure does not always alleviate symptoms or improve exercise capacity, which is possibly explained by impaired left ventricular (LV) haemodynamics. This study evaluated the effect of ASD closure in children using non-invasive LV pressure-volume (PV) loops derived from cardiac magnetic resonance (CMR) imaging and brachial blood pressure, compared with controls. Methods and results: Twenty-three children with ASD underwent CMR, and 17 of them were re-examined 7 (6-9) months after ASD closure. Twelve controls were included. Haemodynamic variables were derived from PV loops by time-resolved LV volumes and brachial blood pressure. After ASD closure, LV volume increased [76 (70-86) vs. 63 (57-70) mL/m2, P = 0.0001]; however, it was still smaller than in controls [76 (70-86) vs. 82 (78-89) mL/m2, P = 0.048]. Compared with controls, children with ASD had higher contractility [2.6 (2.1-3.3) vs. 1.7 (1.5-2.2) mmHg/mL, P = 0.0076] and arterial elastance [2.1 (1.4-3.1) vs. 1.4 (1.2-2.0) mmHg/mL, P = 0.034]. After ASD closure, both contractility [2.0 (1.4-2.5) mmHg/mL, P = 0.0001] and arterial elastance [1.4 (1.3-2.0) mmHg/mL, P = 0.0002] decreased. Conclusion: Despite the left-to-right atrial shunt that leads to low LV filling and RV enlargement, the LV remains efficient and there is no evidence of impaired LV haemodynamics in children. Closure of ASD at young age while the ventricle is compliant is thus beneficial for LV function. LV volumes, however, remain small after ASD closure, which may impact long-term cardiovascular risk and exercise performance.

Theory and Measurement of Heat Transport in Solids: How Rigidity and Spectral Properties Govern Behavior.

Models of heat transport in solids, being based on idealized elastic collisions of gas molecules, are flawed because heat and mass diffuse independently in solids but together in gas. To better understand heat transfer, an analytical, theoretical approach is combined with data from laser flash analysis, which is the most accurate method available. Dimensional analysis of Fourier's heat equation shows that thermal diffusivity (D) depends on length-scale, which has been confirmed experimentally for metallic, semiconducting, and electrically insulating solids. A radiative diffusion model reproduces measured thermal conductivity (K = DρcP = D × density × specific heat) for thick solids from ~0 to >1200 K using idealized spectra represented by 2-4 parameters. Heat diffusion at laboratory temperatures (conduction) proceeds by absorption and re-emission of infrared light, which explains why heat flows into, through, and out of a material. Because heat added to matter performs work, thermal expansivity is proportional to ρcP/Young's modulus (i.e., rigidity or strength), which is confirmed experimentally over wide temperature ranges. Greater uptake of applied heat (e.g., cP generally increasing with T or at certain phase transitions) reduces the amount of heat that can flow through the solid, but because K = DρcP, the rate (D) must decrease to compensate. Laser flash analysis data confirm this proposal. Transport properties thus depend on heat uptake, which is controlled by the interaction of light with the material under the conditions of interest. This new finding supports a radiative diffusion mechanism for heat transport and explains behavior from ~0 K to above melting.

Bladder Compliance Dynamics of Pelvic Organ Prolapse in Women Undergoing Robotic-assisted Sacrocolpopexy.

STUDY OBJECTIVE: Although mean/static compliance of bladder filling can be readily assayed via cystometry, a protocol measuring compliance dynamics at a specific stage of bladder filling has not been established in human patients. For patients with pelvic organ prolapse (POP), the objective benefits of robotic-assisted sacrocolpopexy (RSCP) surgical intervention for restoring bladder functions, primarily urine storage, have yet to be established. Also, bladder compliance is a viscoelastic parameter that crucially defines the storage function. Therefore, we aimed to investigate the impact of RSCP on bladder compliance of POP patients using a pressure-volume analysis (PVA), which graphically illustrates bladder compliance. DESIGN: A retrospective pre and postoperative study. SETTING: Multiple hospitals in Taiwan. PATIENTS: Twenty seven female POP patients (stage ≥ II). INTERVENTION: RSCP for POP repair. MEASUREMENTS AND MAIN RESULTS: We retrospectively reviewed the pre- and postoperative PVAs for women with POP who underwent RSCP. The mean compliance of the entire (Cm), the early half (C1/2), and the late half (C2/2) of bladder filling were analyzed as primary outcomes. Changes in intravesical volume (ΔVive) and detrusor pressure (ΔPdet) of bladder filling, ΔPdet in the early (ΔPdet1/2) and late (ΔPdet2/2) filling, and postvoiding residual volume (Vres) were analyzed as secondary outcomes. Compared with the preoperative control, RSCP increased Cm (p = .010, N = 27) and C2/2 (p <.001, N = 27) but negligibly affected C1/2 (p = .457, N = 27). Mechanistically, RSCP decreased ΔPdet (p = .0001, N = 27) without significantly affecting ΔVive (p = .863, N = 27). Furthermore, RSCP decreased the ΔPdet2/2 (p <.001, N = 27) but not ΔPdet1/2 (p = .295, N = 27). CONCLUSIONS: This is the first report on applying PVA in assaying dynamics of bladder compliance in patients with POP. Our results suggest that RSCP improved bladder storage in women with POP since it increased bladder compliance, particularly in the late filling, possibly by restoring the anatomical location and geometric conformation for bladder expansion.

Water relations and photosystem II efficiency of the intertidal macroalga Fucus virsoides.

Intertidal macroalgae are sessile poikilohydric organisms exposed to desiccation stress during emersion. Water relations parameters are useful tools to evaluate an organism's capacity to withstand water scarcity conditions, but such information on marine intertidal macroalgae is scarce. We assessed the water relations of the intertidal relict Fucus virsoides, the unique Fucus species endemic to the Mediterranean. We combined measurements of water potential (Ψ) parameters derived from pressure-volume curves and chlorophyll a fluorescence (Fv/Fm) in juvenile and adult thalli sampled in three different dates between March and April 2023. F. virsoides exhibited remarkable water stress tolerance, as evidenced by the low water potential at turgor loss point (Ψtlp, -7.0 MPa on average), and the maintenance of high Fv/Fm at low water potentials indicating a prolonged maintenance of healthy physiological status. While no differences were observed between growth stages, Ψtlp, capacitance (C) and the bulk modulus of elasticity (ε) varied significantly according to the sampling dates, whereas the osmotic potential at full turgor did not significantly change. Ψ measured on thalli collected after a typical prolonged emersion period was markedly lower (-12.3 MPa on average) than the estimated Ψtlp, suggesting that the population is frequently undergoing turgor loss. Further investigations are required to determine environmental tolerance ranges based on water status characteristics to enhance our understanding of F. virsoides responses and vulnerability to climate change, thus providing insight into the possible causes of its widespread decline.

Recruitment-Potential-Oriented Mechanical Ventilation Protocol and Narrative Review for Patients with Acute Respiratory Distress Syndrome.

Even though much progress has been made to improve clinical outcomes, acute respiratory distress syndrome (ARDS) remains a significant cause of acute respiratory failure. Protective mechanical ventilation is the backbone of supportive care for these patients; however, there are still many unresolved issues in its setting. The primary goal of mechanical ventilation is to improve oxygenation and ventilation. The use of positive pressure, especially positive end-expiratory pressure (PEEP), is mandatory in this approach. However, PEEP is a double-edged sword. How to safely set positive end-inspiratory pressure has long been elusive to clinicians. We hereby propose a pressure-volume curve measurement-based method to assess whether injured lungs are recruitable in order to set an appropriate PEEP. For the most severe form of ARDS, extracorporeal membrane oxygenation (ECMO) is considered as the salvage therapy. However, the high level of medical resources required and associated complications make its use in patients with severe ARDS controversial. Our proposed protocol also attempts to propose how to improve patient outcomes by balancing the possible overuse of resources with minimizing patient harm due to dangerous ventilator settings. A recruitment-potential-oriented evaluation-based protocol can effectively stabilize hypoxemic conditions quickly and screen out truly serious patients.

Low Ventricular Stiffness Is Associated With Suboptimal Outcomes in Patients With a Single Right Ventricle After the Fontan Operation: A Novel Phenotype.

BACKGROUND: Despite a rigorous screening process, including cardiac catheterization, a subset of patients with a single right ventricle (SRV) demonstrates suboptimal short-term outcomes after the Fontan operation. The goal of this study was to perform a comprehensive assessment of diastolic function in pre-Fontan patients with an SRV using invasive reference-standard measures and determine their associations with post-Fontan outcomes. METHODS AND RESULTS: Children aged 2 to 6 years with SRV physiology undergoing pre-Fontan heart catheterization were recruited prospectively. Patients were divided into those who had an optimal or suboptimal outcome. A suboptimal outcome was defined as length of stay ≥14 days or heart transplant/cardiac death in first year after Fontan. Patients underwent pressure-volume loop analysis using reference-standard methods. The measure of ventricular stiffness, ß, was obtained via preload reduction. Cardiac magnetic resonance imaging for extracellular volume and serum draws for matrix metalloproteinase activity were performed. Of 19 patients with an SRV, 9 (47%) had a suboptimal outcome. Mean age was 4.2±0.7 years. Patients with suboptimal outcomes had lower ventricular stiffness (0.021 [0.009-0.049] versus 0.090 [0.031-0.118] mL-1; P=0.02), lower extracellular volume (25% [28%-32%] versus 31% [28%-33%]; P=0.02), and lower matrix metalloproteinase-2 (90 [79-104] versus 108 [79-128] ng/mL; P=0.01) compared with patients with optimal outcomes. The only invasive measure that had an association with suboptimal outcome was ß (P=0.038). CONCLUSIONS: Patients with an SRV with suboptimal outcome after the Fontan operation had lower ventricular stiffness and evidence of maladaptive extracellular matrix metabolism compared with patients with optimal outcome. This appears to be a novel phenotype that may have important clinical implications and requires further study.

Left and Right Ventricular Hemodynamic Response After Transcatheter Mitral Valve Replacement.

Background: Transcatheter mitral valve replacement (TMVR) represents a novel treatment option for patients with mitral regurgitation (MR), but little is known about the hemodynamic impact of MR elimination following TMVR. We sought to investigate the hemodynamic impact of TMVR on left ventricular (LV) and right ventricular (RV) function using noninvasive pressure-volume loops. Methods: All consecutive patients undergoing TMVR with dedicated devices between May 2016 and August 2022 were enrolled. The end-diastolic and end-systolic pressure-volume relationships were estimated from 26 patients using single-beat echocardiographic measurements at baseline and after TMVR at discharge. RV function was assessed by RV-pulmonary artery (PA) coupling and RV fractional area change. One-year follow-up was available for 19 patients. The prognostic impact of calculated end-diastolic volume at an end-diastolic pressure of 20 mmHg (VPed20) reduction was assessed by Cox regression. Results: A total of 26 patients (77.0 years [interquartile range 73.9-80.1], N = 17 [65.4%] male) with successful TMVR were included (secondary MR [N = 21, 80.8%]; median LV ejection fraction was 37.0% [interquartile range 30.7-50.7]). At discharge, a decrease in VPed20 (p < 0.001) indicating leftward shift of end-diastolic pressure-volume relationship, and an increase of the end-systolic elastance slope (p = 0.007) were observed after TMVR. No changes were observed for RV-PA coupling (p = 0.19) and RV fractional area change (p = 0.22). At 1-year follow-up, LV contractility (end-systolic elastance) and RV-PA coupling remained stable. Vped20 reduction at discharge was significantly associated with 1-year all-cause mortality or heart failure hospitalization (hazard ratio 0.16, 95% CI 0.04-0.71, p = 0.016). Conclusions: Noninvasive assessment of pressure-volume loops demonstrated early LV reverse remodeling and improved LV contractility, while RV performance was preserved. These results indicate the potential prognostic impact of complete MR elimination after TMVR.

Impact of Right Ventricular Pressure Overload on Myocardial Stiffness Assessed by Natural Wave Imaging.

BACKGROUND: Right ventricular (RV) hemodynamic performance determines the prognosis of patients with RV pressure overload. Using ultrafast ultrasound, natural wave velocity (NWV) induced by cardiac valve closure was proposed as a new surrogate to quantify myocardial stiffness. OBJECTIVES: This study aimed to assess RV NWV in rodent models and children with RV pressure overload vs control subjects and to correlate NWV with RV hemodynamic parameters. METHODS: Six-week-old rats were randomized to pulmonary artery banding (n = 6), Sugen hypoxia-induced pulmonary arterial hypertension (n = 7), or sham (n = 6) groups. They underwent natural wave imaging, echocardiography, and hemodynamic assessment at baseline and 6 weeks postoperatively. The authors analyzed NWV after tricuspid and after pulmonary valve closure (TVC and PVC, respectively). Conductance catheters were used to generate pressure-volume loops. In parallel, the authors prospectively recruited 14 children (7 RV pressure overload; 7 age-matched control subjects) and compared RV NWV with echocardiographic and invasive hemodynamic parameters. RESULTS: NWV significantly increased in RV pressure overload rat models (4.99 ± 0.27 m/s after TVC and 5.03 ± 0.32 m/s after PVC in pulmonary artery banding at 6 weeks; 4.89 ± 0.26 m/s after TVC and 4.84 ± 0.30 m/s after PVC in Sugen hypoxia at 6 weeks) compared with control subjects (2.83 ± 0.15 m/s after TVC and 2.72 ± 0.34 m/s after PVC). NWV after TVC correlated with both systolic and diastolic parameters including RV dP/dtmax (r = 0.75; P < 0.005) and RV Ees (r = 0.81; P < 0.005). NWV after PVC correlated with both diastolic and systolic parameters and notably with RV end-diastolic pressure (r = 0.65; P < 0.01). In children, NWV after both right valves closure in RV pressure overload were higher than in healthy volunteers (P < 0.01). NWV after PVC correlated with RV E/E' (r = 0.81; P = 0.008) and with RV chamber stiffness (r = 0.97; P = 0.03). CONCLUSIONS: Both RV early-systolic and early-diastolic myocardial stiffness show significant increase in response to pressure overload. Based on physiology and our observations, early-systolic myocardial stiffness may reflect contractility, whereas early-diastolic myocardial stiffness might be indicative of diastolic function.

Unique root hydraulic and mechanical properties support the resilience of grapevines adapted to the Atacama Desert.

Cortical lacunae caused by drought, especially observed in hybrids originating from Vitis rupestris, disrupt the connection between roots and soil. Yet, the physiological processes behind lacuna formation during drought and its consistency across Vitis species remain unclear. Here, we used a root pressure probe to investigate fine root hydraulic and mechanical properties, in the arid-adapted R-65 and drought-susceptible 101-14Mgt cultivars. We then performed P-V curves, root sap osmolality, and electrolyte leakage (EL) and used fluorescent light microscopy techniques. Only 101-14Mgt showed lacunae formation during drought due to its stiffer cortical tissue, unlike R-65. Lacunae resulted in a notable decline in root hydraulic conductivity during severe drought, with increased EL and root sap osmolality, indicating potential cellular damage. R-65 displayed different and xerophyte-like characteristics featuring a higher turgor loss point and decreased root capacitance, essential for maintaining root structural integrity in arid conditions. Our findings highlight lacuna formation is impacted by root tissue elasticity possibly linked to specific Vitis species favoring deeper rooting. In arid-adapted grapevines, hydraulic regulators such as reduced turgor loss point, and root capacitance could contribute to enhanced drought tolerance.

Analysis of warpage and reliability of very thin profile fine pitch ball grid array.

With the evolution of advanced integrated circuit (IC) packaging technology, the use of experiments to identify package performance and life expectation will take a significant amount of time and cost to finish the job. To reduce the cost of research and testing, predictive analyses of reliability and performance using simulation tools have become a feasible approach for the IC assembly industry. Therefore, this study utilized Moldex3D molding simulation software to analyze very thin profile fine pitch ball grid array (VFBGA) packages and established a numerical analysis procedure from the molding and curing process, the post-mold cure (PMC) process, to a thermal cycling test (TCT) to predict the amount of package warpage during processing and reliability after TCT. The results showed that the warpage trends of both experiments and simulations during the same temperature ramping process were similar. In the thermal cycling analysis, potential failure locations were found to be at the copper pillars and redistribution layer (RDL), where the maximum Von Mises stress occurred at the lowest temperature (-65 °C). The fatigue life model, Coffin-Manson model, was used to calculate the potential fatigue life at the two locations, resulting in 1689 cycles (copper pillars) and 9706 cycles (RDL L1).

Alveolar wall hyperelastic material properties determined using alveolar cluster model with experimental stress-stretch and pressure-volume data.

Micro-scale models of lung tissue have been employed by researchers to investigate alveolar mechanics; however, they have been limited by the lack of biofidelic material properties for the alveolar wall. To address this challenge, a finite element model of an alveolar cluster was developed comprising a tetrakaidecahedron array with the nominal characteristics of human alveolar structure. Lung expansion was simulated in the model by prescribing a pressure and monitoring the volume, to produce a pressure-volume (PV) response that could be compared to experimental PV data. The alveolar wall properties in the model were optimized to match experimental PV response of lungs filled with saline, to eliminate surface tension effects and isolate the alveolar wall tissue response. When simulated in uniaxial tension, the model was in agreement with reported experimental properties of uniaxial tension on excised lung tissue. The work presented herein was able to link micro-scale alveolar response to two disparate macroscopic experimental datasets (stress-stretch and PV response of lung) and presents hyperelastic properties of the alveolar wall for use in alveolar scale finite element models and multi-scale models. Future research will incorporate surface tension effects, and investigate alveolar injury mechanisms.

Machine learning prediction of methane, nitrogen, and natural gas mixture viscosities under normal and harsh conditions.

The accurate estimation of gas viscosity remains a pivotal concern for petroleum engineers, exerting substantial influence on the modeling efficacy of natural gas operations. Due to their time-consuming and costly nature, experimental measurements of gas viscosity are challenging. Data-based machine learning (ML) techniques afford a resourceful and less exhausting substitution, aiding research and industry at gas modeling that is incredible to reach in the laboratory. Statistical approaches were used to analyze the experimental data before applying machine learning. Seven machine learning techniques specifically Linear Regression, random forest (RF), decision trees, gradient boosting, K-nearest neighbors, Nu support vector regression (NuSVR), and artificial neural network (ANN) were applied for the prediction of methane (CH4), nitrogen (N2), and natural gas mixture viscosities. More than 4304 datasets from real experimental data utilizing pressure, temperature, and gas density were employed for developing ML models. Furthermore, three novel correlations have developed for the viscosity of CH4, N2, and composite gas using ANN. Results revealed that models and anticipated correlations predicted methane, nitrogen, and natural gas mixture viscosities with high precision. Results designated that the ANN, RF, and gradient Boosting models have performed better with a coefficient of determination (R2) of 0.99 for testing data sets of methane, nitrogen, and natural gas mixture viscosities. However, linear regression and NuSVR have performed poorly with a coefficient of determination (R2) of 0.07 and - 0.01 respectively for testing data sets of nitrogen viscosity. Such machine learning models offer the industry and research a cost-effective and fast tool for accurately approximating the viscosities of methane, nitrogen, and gas mixture under normal and harsh conditions.

Science of left ventricular unloading.

The concept of left ventricular unloading has its foundation in heart physiology. In fact, the left ventricular mechanics and energetics represent the cornerstone of this approach. The novel sophisticated therapies for acute heart failure, particularly mechanical circulatory supports, strongly impact on the mechanical functioning and energy consuption of the heart, ultimately affecting left ventricle loading. Notably, extracorporeal circulatory life support which is implemented for life-threatening conditions, may even overload the left heart, requiring additional unloading strategies. As a consequence, the understanding of ventricular overload, and the associated potential unloading strategies, founds its utility in several aspects of day-by-day clinical practice. Emerging clinical and pre-clinical research on left ventricular unloading and its benefits in heart failure and recovery has been conducted, providing meaningful insights for therapeutical interventions. Here, we review the current knowledge on left ventricular unloading, from physiology and molecular biology to its application in heart failure and recovery.

Personalized evaluation of the passive myocardium in ischemic cardiomyopathy via computational modeling using Bayesian optimization.

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure-volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine.