Evaluation of vascular aging on measures of cardiac function and mechanical efficiency: insights from in-silico modeling.

Introduction: This study evaluated the hypothesis that vascular aging (VA) reduces ventricular contractile function and mechanical efficiency (ME) using the left ventricular pressure-volume (PV) construct. Methods: A previously published in-silico computational model (CM) was modified to evaluate the hypothesis in two phases. In phase I, the CM included five settings of aortic compliance (CA) from normal to stiff, studied at a heart rate of 80 bpm, and phase II included the normal to stiff CA settings evaluated at 60, 100, and 140 bpm. The PV construct provided steady-state and transient data through a simulated vena caval occlusion (VCO). The steady-state data included left ventricular volumes (EDV and ESV), stroke work (SW), and VCO provided the PV area (PVA) data in addition to the three measures of contractile state (CS): end-systolic pressure-volume relationship (ESPVR), dP/dtmax-EDV and preload recruitable stroke work (PRSW). Finally, ME was calculated with the SW/PVA parameter. Results: In phase I, EDV and ESV increased, as did SW and PVA. The impact on the CS parameters demonstrated a small decrease in ESPVR, no change in dP/dtmax-EDV, and a large increase in PRSW. ME decreased from 71.5 to 60.8%, respectively. In phase II, at the normal and stiff CA settings, across the heart rates studied, EDV and ESV decreased, ESPVR and dP/dtmax-EDV increased and PRSW decreased. ME decreased from 76.4 to 62.6% at the normal CA and 65.8 to 53.2% at the stiff CA. Discussion: The CM generated new insights regarding how the VA process impacts the contractile state of the myocardium and ME.

Erratum: Resolving an inconsistency in the estimation of the energy for excitation of cardiac muscle contraction.

[This corrects the article DOI: 10.3389/fphys.2023.1269900.].

Resolving an inconsistency in the estimation of the energy for excitation of cardiac muscle contraction.

In the excitation of muscle contraction, calcium ions interact with transmembrane transporters. This process is accompanied by energy consumption and heat liberation. To quantify this activation energy or heat in the heart or cardiac muscle, two non-pharmacological approaches can be used. In one approach using the "pressure-volume area" concept, the same estimate of activation energy is obtained regardless of the mode of contraction (either isovolumic/isometric or ejecting/shortening). In the other approach, an accurate estimate of activation energy is obtained only when the muscle contracts isometrically. If the contraction involves muscle shortening, then an additional component of heat associated with shortening is liberated, over and above that of activation. The present study thus examines the reconcilability of the two approaches by performing experiments on isolated muscles measuring contractile force and heat output. A framework was devised from the experimental data to allow us to replicate several mechanoenergetics results gleaned from the literature. From these replications, we conclude that the choice of initial muscle length (or ventricular volume) underlies the divergence of the two approaches in the estimation of activation energy when the mode of contraction involves shortening (ejection). At low initial muscle lengths, the heat of shortening is relatively small, which can lead to the misconception that activation energy is contraction mode independent. In fact, because cardiac muscle liberates heat of shortening when allowed to shorten, estimation of activation heat must be performed only under isometric (isovolumic) contractions. We thus recommend caution when estimating activation energy using the "pressure-volume area" concept.

Reshaping the Ventricle From Within: MIRTH (Myocardial Intramural Remodeling by Transvenous Tether) Ventriculoplasty in Swine.

MIRTH (Myocardial Intramural Remodeling by Transvenous Tether) is a transcatheter ventricular remodeling procedure. A transvenous tension element is placed within the walls of the beating left ventricle and shortened to narrow chamber dimensions. MIRTH uses 2 new techniques: controlled intramyocardial guidewire navigation and EDEN (Electrocardiographic Radial Depth Navigation). MIRTH caused a sustained reduction in chamber dimensions in healthy swine. Midventricular implants approximated papillary muscles. MIRTH shortening improved myocardial contractility in cardiomyopathy in a dose-dependent manner up to a threshold beyond which additional shortening reduced performance. MIRTH may help treat dilated cardiomyopathy. Clinical investigation is warranted.

The Left Ventricular Pressure-Volume Area and Stroke Work in Porcine Model of Ascending Compared to Descending Thoracic Aorta Stenosis Creating a Chronic Early Vs. Late Left Ventricular Afterload Increase.

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.

Invasive Cardiomechanics During Transcatheter Edge-to-Edge Repair for Massive Tricuspid Regurgitation Using Biventricular Pressure-Volume Loop Monitoring.

Invasive pressure-volume loop analysis allows direct monitoring of changing intraventricular cardiac mechanics during structural heart interventions. Our aim was to illustrate changes in right and left ventricular mechanics during transcatheter edge-to-edge tricuspid repair for severe tricuspid regurgitation. (Level of Difficulty: Advanced.).

Cardiac Mechanoenergetics in Patients with Acute Myocardial Infarction: From Pressure-Volume Loop Diagram Related to Cardiac Oxygen Consumption.

Acute myocardial infarction (AMI) results in significant changes in cardiac structure and functions, leading to left ventricular remodeling and subsequent systolic and diastolic dysfunction. To improve current approaches in diagnoses, treatments, and prevention of cardiovascular diseases, a better understanding of cardiac mechanoenergetics, including systolic performance and energy demand, becomes paramount. In this review, we summarize cardiac mechanics, cardiac energetics, and their relationship in complications related to AMI using 2 important physiologic frameworks, pressure-volume loops and the Vo2-pressure-volume area relationship diagram, as they are powerful tools for understanding physiologic behavior and mechanoenergetics of the left ventricle.

The energy-saving effect of a new myosin activator, omecamtiv mecarbil, on LV mechanoenergetics in rat hearts with blood-perfused isovolumic contraction model.

A novel myosin activator, omecamtiv mecarbil (OM), is a cardiac inotropic agent with a unique new mechanism of action, which is thought to arise from an increase in the transition rate of myosin into the actin-bound force-generating state without increasing calcium (Ca2+) transient. There remains, however, considerable controversy about the effects of OM on cardiac contractility and energy expenditure. In the present study, we investigated the effects of OM on left ventricular (LV) mechanical work and energetics, i.e., mechanoenergetics in rat normal hearts (CTL) and failing hearts induced by chronic administration of isoproterenol (1.2 mg/kg/day) for 4 weeks (ISO-HF). We analyzed the LV end-systolic pressure-volume relation (ESPVR) and the linear relation between the myocardial oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA; a total mechanical energy per beat) in isovolumically contracting rat hearts at 240- or 300-bpm pacing in the absence or presence of OM. OM did not change the ESPVR in CTL and ISO-HF. OM, however, significantly decreased the slope of VO2-PVA relationship in both CTL and ISO-HF, and significantly increased the mean VO2 intercept without changes in basal metabolism in ISO-HF. These results suggested that OM improved the oxygen cost of PVA (contractile efficiency) with the unchanged LV contractility in both CTL and ISO-HF but increased VO2 for Ca2+ handling in excitation-contraction (E-C) coupling in ISO-HF. We concluded that OM improves contractile efficiency in normal and failing hearts but increases O2 consumption of Ca2+ handling in failing hearts in isovolumically contracting rat model.

How can LVAD support influence ventricular energetics parameters in advanced heart failure patients? A retrospective study.

BACKGROUND AND OBJECTIVE: Here we present a retrospective analysis of six heart failure patients previously discussed at a multidisciplinary team meeting. Only three out of six patients underwent LVAD insertion as the most appropriate management option. METHODS: We sought to reproduce the baseline conditions of these patients on hospital admission using our cardiovascular software simulator (CARDIOSIM©). Subsequently, we simulated the effects of LVAD support and drug administration on left and right ventricular energetics parameters. LVAD assistance was delivered by CARDIOSIM© based on the module reproducing the behaviour of the Berlin Heart INCOR pump. RESULTS: The results of our simulations were in agreement with the multidisciplinary team meeting outcome. The analysis of ventricular energetics parameters based on external work and pressure volume area confirmed LVAD support as a beneficial therapeutic option for the three patients considered eligible for this type of treatment. The effects induced by LVAD support and drugs administration showed specific patterns between the two groups of patients. CONCLUSION: A quantitative approach with the ability to predict outcome during patient's assessment may well be an aid and not a substitute for clinical decision-making.