Left Ventricular Pressure Research Articles

Precise Monitoring of Transpulmonic Resistance in Bridge to Transplant Patients Supported by The Aeson Total Artificial Heart.

The Aeson Total Artificial Heart (TAH) features embedded pressure sensors for flow autoregulation, which can also be used to estimate pressure gradients. In this bridge-to-transplant study, right and left ventricular pressure data and pump output from the TAH were analyzed to estimate trans-pulmonic resistance (eTPR) every 30 days. Three patients (aged 60, 35, and 54) with pre-implant pulmonary vascular resistance of 7.0, 3.2, and 7.1 Wood Units, respectively, were supported by the TAH at pump outputs of 4.5-6.5 L/min. All showed significant eTPR reductions (1.4-1.5 Wood Units) and received donor hearts after 243, 155, and 109 days of support. Two patients underwent successful transplants without complications; one died post-transplant from pneumonia and multiorgan failure. The Aeson TAH's eTPR monitoring system offers a promising, non-invasive approach to managing pulmonary hypertension and assessing transplant eligibility in real time.

Numerical Simulation of Fluid-Structure Interaction in Axillary Artery Venoarterial Extracorporeal Membrane Oxygenation for Heart Failure Patients.

Although axillary artery venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been utilized as a mechanical circulatory support for patients with end-stage heart failure (HF), there is currently insufficient evidence to support its effectiveness and safety. The objective of this study was to analyze the hemodynamic effects of axillary artery VA-ECMO. To this end, we obtained CT angiographic imaging data of the aorta from a carefully selected heart failure patient with a cardiac output of 2.1 L/min. These data were used to construct a detailed fluid-structure interaction model of the aorta. Axillary artery VA-ECMO was then simulated within this model, maintaining a constant flow rate of 3 L/min. The intra-aortic balloon counterpulsation (IABP) balloon was simulated to inflate and deflate in synchrony with the diastolic and systolic phases of the cardiac cycle. Hemodynamic effects, including left ventricular (LV) pressure afterload, vessel wall stress, perfusion of vital organs, blood flow pulsatility, and the watershed region, were calculated using fluid-structure interaction analysis. We found that axillary artery VA-ECMO delivers well-distributed, oxygen-rich blood flow but may increase left ventricular (LV) afterload and reduce cerebral blood flow. However, when combined with IABP, it unloads LV pressure and increases cerebral blood flow. Integrating axillary artery VA-ECMO with IABP can promote cardiac function recovery and improve oxygen-rich blood perfusion to the vital organs of heart failure patients.

Chest pain and coronary artery disease in cardiac amyloidosis: Prevalence, mechanisms, and clinical implications.

Amyloidosis is a systemic disease affecting multiple organs, and often presents with cardiac involvement, with 2 primary underlying pathologies: amyloid light chain- and transthyretin cardiac amyloidosis. Chest pain can occur in both types with variable clinical presentations. This narrative review describes the relationship between cardiac amyloidosis (CA) and chest pain. A PubMed search (June 03. 2024) identified 393 articles related to chest pain in CA. Twenty-eight studies, in English and with full text, were selected. Articles included were case reports, reviews, perfusion- and autopsy studies. In CA patients 10%-20% report chest pain as the initial symptom preceding the diagnosis, and the overall prevalence of chest pain is 38% of patients with CA and it is related to an increased risk of heart failure hospitalization. The mechanisms leading to chest pain in CA patients include increased left ventricular diastolic pressure, infiltration of amyloid fibrils inside and around coronary arteries, and amyloid compression of the microvasculature. The mechanisms commonly lead to elevations of plasma troponin levels, which are higher in amyloid patients with chest pain compared to amyloid patients without chest pain. Symptomatic treatment of chest pain can be challenging due to the low tolerability of medical therapy and poor outcomes of coronary interventions in alleviating the pain and with a higher rate of complications. Our review underscores the importance of recognizing chest pain as a CA symptom, particularly in the elderly. Persistent troponin elevation without coronary artery disease could indicate CA. Screening-based and longitudinal studies are crucial for understanding the relationship between chest pain and CA. Acknowledging the significance of chest pain in CA may facilitate early intervention and improve patient outcomes.

Pimobendan oral solution is bioequivalent to pimobendan chewable tablets in beagle dogs.

Myxomatous mitral valve disease (MMVD) is frequently diagnosed in small breed dogs. Pimobendan oral solution has been developed to improve dosing accuracy in small and toy breed dogs. Demonstrate bioequivalence of pimobendan oral solution with pimobendan chewable tablets using a pharmacokinetic and a pharmacodynamic study in healthy purpose bred dogs. In the pharmacokinetic study, 24 beagle dogs were dosed in a 4-period crossover design. In the pharmacodynamic study, 4 mongrel and 2 beagle dogs implanted with telemetry probes were included in a 2-way crossover design. Both studies were designed as prospective, randomized crossover trials. Dogs were given single doses of 5 mg/dog of either formulation followed by serial blood sampling for determination of pimobendan and O-desmethyl-pimobendan (ODMP; main metabolite). Because of high variability in the pharmacokinetics, the reference scaled average bioequivalence (RSABE) method was applied. For the pharmacodynamic study, animals were dosed with 0.25 mg/kg of either formulation. Baseline corrected left ventricular maximal pressure (LVdP/dtmax) and heart rate were recorded continuously and compared with a predefined bioequivalence threshold. Pimobendan was verified as a high variability drug. Based on the RSABE method, both formulations were bioequivalent. Pharmacodynamic results supported bioequivalence. The novel oral solution of pimobendan was found to be bioequivalent, both applying the Food and Drug Administration (FDA) supported RSABE method and based on pharmacodynamic data. Thus, the novel liquid formulation can be used to facilitate accurate dosing of small and toy breed dogs.

Super-resolution left ventricular flow and pressure mapping by Navier-Stokes-informed neural networks.

Intraventricular vector flow mapping (VFM) is an increasingly adopted echocardiographic technique that derives time-resolved two-dimensional flow maps in the left ventricle (LV) from color-Doppler sequences. Current VFM models rely on kinematic constraints arising from planar flow incompressibility. However, these models are not informed by crucial information about flow physics; most notably the forces within the fluid and the resulting accelerations. This limitation has rendered VFM unable to combine information from different time frames in an acquisition sequence or derive fluctuating pressure maps. In this study, we leveraged recent advances in artificial intelligence (AI) to develop AI-VFM, a vector flow mapping modality that uses physics-informed neural networks (PINNs) encoding mass conservation and momentum balance inside the LV, and no-slip boundary conditions at the LV endocardium. AI-VFM recovers the flow and pressure fields in the LV from standard echocardiographic scans. It performs phase unwrapping and recovers flow data in areas without input color-Doppler data. AI-VFM also recovers complete flow maps at time points without color-Doppler input data, producing super-resolution flow maps. We validate AI-VFM using physiological simulated LV data and show that informing the PINNs with momentum balance is essential for achieving temporal super-resolution and significantly increases the accuracy of AI-VFM compared to informing the PINNs only with mass conservation. AI-VFM is solely informed by each patient's flow physics; it does not utilize explicit smoothness constraints or incorporate data from other patients or flow models. AI-VFM takes 15 min to run in off-the-shelf graphics processing units and its underlying PINN framework could be extended to map other flow-associated metrics such as blood residence time or the concentration of coagulation species.

A new HCM heart sound classification method based on weighted bispectrum features.

Hypertrophic cardiomyopathy (HCM), including obstructive HCM and non-obstructive HCM, can lead to sudden cardiac arrest in adolescents and athletes. Early diagnosis and treatment through auscultation of different types of HCM can prevent the occurrence of malignant events. However, it is challenging to distinguish the pathological information of HCM related to differential left ventricular outflow tract pressure gradients. To address this issue, a classification method based on weighted bispectrum features of heart sounds (HSs) is proposed for efficient and cost-effective HCM analysis. Preprocessing is first applied to remove background noise during HS acquisition. Then, the bispectrum contour map is calculated, and 56-dimensional features are extracted to represent the pathological information of HCM. Next, an adaptive threshold weighting mutual information method is proposed for feature selection and weighted fusion. Finally, the CNN-RF classifier model is built to automatically identify different types of HCM cases. A clinical dataset of normal and two types of HCM HSs is utilized for validation. The results show that the proposed method performs well, with a classification accuracy reaching 94.4%. It provides a reliable reference for HCM diagnosis in young patients in clinical settings.

Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis.

Objective indices of functional capacity in patients with diabetic cardiomyopathy and stage B heart failure (HF) have not been comprehensively defined. We sought to characterize the cardiopulmonary exercise characteristics of individuals with diabetic cardiomyopathy at high risk for overt HF. The relationships from cardiopulmonary exercise testing with clinical and laboratory characteristics of participants with diabetic cardiomyopathy were evaluated using baseline data from the ARISE-HF trial (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure). Cluster phenogroups with different comorbidities and their corresponding functional capacity profiles were identified. Among study participants (n=689), the median (Q1, Q3) peak oxygen uptake and ventilatory efficiency (slope of the ratio of minute ventilation/carbon dioxide production) were 15.7 (interquartile range, 13.0-18.0) mL/kg per minute and 31.2 (interquartile range, 27.2-34.1), respectively. Lower peak oxygen uptake was associated with older age, female sex, higher body mass index, higher N-terminal pro-B-type natriuretic peptide, and an increasing burden of noncardiac comorbid conditions but was not associated with cardiac troponin T or echocardiogram-derived strain, left atrial volume index, E/e', or right ventricular systolic pressure. Elevated left ventricular mass index was the only echocardiographic abnormality associated with lower peak oxygen uptake. Multivariable analysis revealed that female sex, higher body mass index, and no history of dyslipidemia were independently associated with lower baseline peak oxygen uptake. Cluster analysis revealed 3 clusters with profiles of different cardiovascular/exercise parameters and health status profiles. Baseline cardiopulmonary exercise testing data from the ARISE-HF trial highlight predominant associations of extracardiac clinical and demographic variables with significant impairment in exercise capacity despite strict fulfillment of diagnostic criteria for stage B HF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04083339.

Pressure-volume analysis by three-dimensional echocardiography: an accurate non-invasive alternative for assessing left ventricular contractility

Abstract Introduction Accurately assessing left ventricular (LV) contractility is vital for diagnosing and managing cardiac conditions like heart failure, cardiomyopathies, and ischemic heart disease. LV contractility assessment by traditional invasive pressure-volume (PV) analysis necessitates invasive measurements, introducing significant risks and limitations. However, three-dimensional (3D) echocardiography and non-invasive LV pressure curve estimation enables accurate PV-loop estimation, presenting a harmless and widely available alternative for LV contractility assessment. Aim Validate indices of LV contractility by PV analysis using 3D echocardiography by comparing them to gold-standard invasive measurements. Methods In 10 open-chest canines, invasive LV pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Echocardiography provided non-invasive 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting a reference curve to the valve events and measured peak LV pressure. Invasive LV end-systolic elastance (Ees) was obtained from multiple PV -loops during preload reduction through least square regression of the points on the PV-loops in the upper left corner with longest normalized distance from loop center. Non-invasive Ees was estimated using a simplified one-beat approach as the slope of a line drawn from this PV-loop point to the origin (Figure 1A). Invasive and non-invasive Ees, along with contractility indices peak LV pressure (Pmax)/end-diastolic volume (EDV) and LV pressure at end-systole (Pes)/EDV, were compared during baseline and during dobutamine infusion. Results As shown in the representative experiment illustrated in Figure 1A, non-invasive Ees captured changes in LV contractility in a similar manner as compared to invasive Ees. Indeed, this was consistent across all experiments, resulting in significant increase in non-invasive Ees in parallel with invasive Ees during dobutamine infusion (p < 0.001 for both) (Figure 1B). Consequently, there was a strong correlation and good agreement between the two methods (r = 0.63, p = 0.003; mean difference – 1.5, SD 2.4) (Figure 1C). For LV contractility indices Pmax/EDV and Pes/EDV, results were comparable: both increased significantly during dobutamine infusion, similar to invasive Ees. This was consistent across all experiments, without exceptions (Figure 2A). Consequently, there were strong correlations between Pmax/EDV and Pes/EDV and invasive Ees (r = 0.77, p = 0.0001 and r = 0.79, p < 0.0001, respectively) (Figure 2B). Conclusions 3D echocardiography provides a reliable and non-invasive method for assessing LV contractility, with good agreement with traditional invasive gold standard Ees. These findings support the use of 3D echocardiography as an accurate and easily accessible alternative for evaluating LV contractility in clinical settings. Invasive vs non-invasive LV Ees Pmax/EDV and Pes/EDV

Myocardial work and extravalvular cardiac damage stages: hand-in-hand predictors of all-cause mortality in patients undergoing transcatheter aortic valve replacement

Abstract In patients with aortic stenosis (AS) evaluating left ventricular (LV) systolic function is challenging due to the influence of increased afterload on traditional measures. Myocardial work (MW) analysis, a novel echocardiographic method, adjusts myocardial deformation to instantaneous LV pressure, providing a more accurate reflection of LV contractile state. Notably, prolonged LV pressure overload induces significant backward effects beyond the LV; the classification of this extravalvular cardiac damage effectively represents the cardiopulmonary system's involvement in AS. Both MW analysis and cardiac damage staging may possess significant prognostic value in the clinically complex cohort of transcatheter aortic valve replacement (TAVR) candidates. Thus, our objective was to evaluate the prognostic value of MW analysis and cardiac damage staging in TAVR patients. We enrolled 314 patients (79±6 years, 40% female) prior to TAVR. Echocardiographic assessments were conducted one day before the procedure. LV ejection fraction (EF) was calculated, global longitudinal strain (GLS) was measured using speckle-tracking echocardiography. LV pressure was estimated from systolic blood pressure and transaortic mean gradient, and global constructive work (GCW) was quantified using dedicated software. Based on echocardiographic data, we determined the extent of cardiac damage associated with AS, categorizing patients into Stage 0 (no cardiac damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (pulmonary artery vasculature or tricuspid valve damage), or Stage 4 (right ventricular damage). The primary endpoint was all-cause mortality, reached by 69 patients during a median follow-up period of 25 months. Preprocedural EF was 47±13 %, GLS was -12.3±4.2 %, GCW was 2043±769 mmHg%. 14 (5%) patients were classified as Stage 0, 61 (20%) as Stage 1, 133 (43%) as Stage 2, 22 (7%) as Stage 3, and 74 (24%) as Stage 4. GCW showed a decline through AS Stages (from Stage 0-4: 2963±652 vs. 2154±621 vs. 2174±706 vs. 2044±827 vs. 1553±757 mmHg%; p<0.001). Using univariate Cox analysis GCW (HR 0.968 [95% CI 0.938-0.998] per 100 unit change; p=0.034) and AS Staging (HR 1.236 [95% CI 1.016-1.505]; p=0.034) were associated with all-cause mortality, while EF (HR 0.982 [95% CI 0.964-1.001]; p=NS) and GLS (HR 1.047 [95% CI 0.989-1.108]; p=NS) were not. In multivariate Cox regression models, both GCW (HR 0.958 [95% CI 0.923-0.994] per 100 unit change; p=0.022) and AS cardiac damage staging (HR 1.281 [95% CI 1.040-1.577]; p=0.020) were significant independent predictors of all-cause mortality. In TAVR patients, preoperative GCW values continuously decreased across all AS Stages. GCW and AS Staging showed strong association with all-cause mortality in our cohort, while EF and GLS did not. Furthermore, GCW and AS Staging had higher prognostic value than any other echocardiographic measure, highlighing their role in preprocedural assessment before TAVR.

Initial insights into left ventricular mechanics of hypertrophic cardiomyopathy patients during follow up of mavacamten therapy

Abstract Introduction Mavacamten is a novel therapy for hypertrophic obstructive cardiomyopathy. Left ventricular (LV) ejection fraction (EF) has been used for monitoring of left ventricular systolic function during therapy. Currently there is limited data on advanced functional parameters based on speckle tracking strain values, such as global longitudinal strain (GLS) , myocardial work (MW) or 3D echocardiography. MW is an emerging method which incorporates left ventricular pressure and provides multiple parameters based on a LV pressure-strain loop. This study aimed to provide some insights into temporal changes of left ventricular deformation during mavacamten therapy. Purpose The purpose of this study was to examine left ventricular global and segmental strains and myocardial work parameters during mavacamten therapy. Methods The study involved 10 (5 women, 50%; aged 57±11 years) cases of mavacamten initiation and echocardiographic follow up (10 patients followed up to visit 1: 48±4.3 days, and 9 patients followed up to visit 2: 129±2.9 days). Comprehensive 2D and 3D resting echocardiography was performed. Speckle tracking based left ventricular strain values were measured. With a previously validated method left ventricular pressure was corrected for measurement of myocardial work parameters. The regional 2D based, LV strain and MW parameters were also examined. Results At the first follow up left ventricular obstruction gradient was already significantly lower compared to baseline and remained decreased at the second follow up (113±36 vs. 37±35 vs. 20±19 mmHg). EF or GLS did not differ significantly between visits (63.8±5.1 vs. 62.5±4.7 vs. 60.9±4.4 %, and -14.5±2.9 vs. -13.9±2.3 vs. -15.6±2.3 % respectively). Global Work Index (GWI) (2026±364 vs. 1588±351 vs. 1578±219 mmHg) and Global Constructive Work (2617±395 vs. 2010±400 vs. 1959±296 mmHg) significantly reduced at both visits when compared to baseline, but not between follow up visits. Global Wasted Work (GWW) (280±117 vs. 245±125 vs. 186±49) and Global Work Efficiency (GWE) (85.6±3.9 vs. 86.6±5.2 vs. 88.8±7.2 %) did not change significantly during follow up, similarly to no changes in 3D based strain, and rotational parameters. Peak Strain Dispersion, (102.8±40.7 vs. 93.8±35.3 vs. 75.9±29.8 ms). 3D based LV Mass (257±75 vs. 248±44 vs. 226±71 g) and Mass Index (137±44 vs. 131±42 vs. 119±41 g/m2) decreased at visit 2, but not at visit 1. The segmental analysis proved significant changes during follow-up compared to baseline in longitudinal strain (2 segments), MW (12 segments) wasted work (1 segment) and work efficiency (2 segments). Conclusions Among left ventricular functional parameters myocardial work has shown the most statistically significant differences during follow up, highlighting the reduction of the LV workload. The analysis of segmental data has shown a heterogeneous pattern of changes, primarily in MW.

Myocardial work analysis of aortic stenosis parients with right ventricular pacing: interaction of afterload and mechanical dyssynchrony?

Abstract It is well known that left ventricular (LV) performance is substantially influenced by the corresponding loading conditions and LV synchrony. Notably, data are scarce about the interaction of these factors: previous studies suggest that patients with left bundle branch block (LBBB) has increased afterload sensitivity. This phenomenon may have special importance in certain clinical situations, such as aortic stenosis (AS) patients with concomitant right ventricular pacing (RVP). Accordingly, our aim was to investigate the effects of RVP on LV function in patients with severe AS before and after transcatheter aortic valve replacement (TAVR). Patients with a previously implanted pacemaker and significant AS undergoing TAVR in our Institute were screened. Only subjects with intrinsic non-LBBB QRS were enrolled (n=31). Detailed echocardiographic protocol suitable for speckle-tracking and myocardial work analysis was obtained. Myocardial work measures were calculated by estimating LV pressure as the sum of the systolic blood pressure and the mean aortic gradient. The patients underwent two sets of echocardiographic examinations: one with their narrow QRS rhythm and one with RVP. Those patients (n=19), who did not develop LBBB or complete AV-block also underwent a post-TAVI protocol. We measured LV ejection fraction (EF), global longitudinal strain (GLS) and also global work index (GWI) and global wasted work (GWW). Preoperatively, RVP resulted in significantly lower LV EF (55±9 vs. 49±10%, p≤0.001), GLS (-14.2±3.6 vs. -11.9±3.5%, p≤0.001) and GWI (1830±502 vs. 1322±546 mmHg%, p≤0.001) compared to narrow QRS rhythm, while GWW was markedly higher (222±129 vs. 344±146 mmHg%, p≤0.001). After TAVR, LV EF was comparable (55±9 vs. 52±8%, p=0.11), while GLS (-13.8±.3.8 vs. -11.4±3.8%, p≤0.001) and GWI (1360±403 vs. 1018±385 mmHg%, p≤0.01) was lower in RVP. Notably, the relative change in GWI in response to RVP was significantly lower after TAVR (-31±21 vs. -22±20%, p≤0.05). In patients with severe AS, LV dyssynchrony associated with RVP results in markedly lower LV functional measures. TAVR alleviates LV pressure overload, and the detrimental effect of RVP may dampen with the afterload reduction. Significant AS and RVP may have a highly unfavorable interaction raising the need for early interventions in this population.

Correlations between ventricular arterial coupling and myocardial work indices in healthy subjects: a speckle tracking echocardiography study

Abstract Background The interaction between left ventricular (LV) function and arterial afterload, defined as ventricular-arterial coupling (VAC), is a key determinant of cardiovascular (CV) performance. The echocardiographic assessment of VAC by the ratio of effective arterial elastance (Ea) to LV end-systolic elastance (Ees) is the most used non-invasive method. Recently, the myocardial work index (MWI) is proposed as a novel VAC non-invasive method. This method, integrating LV pressure (using a brachial cuff), and LV global longitudinal strain (GLS) by speckle tracking echocardiography (STE) to derive pressure-strain loops (PSL), provides a loading-independent evaluation of myocardial systolic performance. Purpose To assess the relationships between VAC, assessed by the Ea/Ees ratio, MW indices, and echocardiographic parameters of LV function in healthy adult subjects. Methods Healthy adult volunteers, without CV risk factors or any medical history, were prospectively enrolled (2019-2024). Age, height, weight, blood pressure (BP) and an ECG tracing to confirm the sinus rhythm were recorded at the time of the comprehensive echocardiogram in all subjects. Global MW indices - index (GWI), constructive (GCW), efficiency (GWE), and wasted (GWW) - were estimated using a commercially available software, from a non-invasive LVPSL, based on STE-derived GLS and estimated LV pressure. The Ea and Ees were expressed as end-systolic pressure (ESP) divided by stroke volume (SV)(ESP/SV) and ESP divided by end-systolic volume (ESP/ESV). VAC was calculated with the simplified formula Ea/Ees =ESV/SV (SV derived from the Biplane method). Off-line data analysis was performed with a dedicated software by a single experienced investigator. Results The study group included 65 subjects (55% males, mean age 33±12 years). The univariate analysis showed significant inverse correlations between Ea/Ees and age, GWI, GCW, GWE, GLS. Ea/Ees correlated with LVSVi and LVEF, as expected. Among MW indices, GWI was the only correlated with age (p<0.001, r= 0.44). Significant correlations were found between MW indices and conventional parameters of LV size and function: GWI with E/e’average (p=0.04, r=0.26), LV mass index (LVMi) (p=0.01, 3=0.35), LVEF (p<0.001, r=0.48); GCW with LVMi (p=0.04, r=0.28) and LVEF (p<0.001, r=0.44). The only correlate of GWW and GWE was LV peak strain dispersion by STE. All MW indices correlated with BP and GLS as expected. On multivariable analysis, GWI was the only independent correlate of Ea/Ees(p<0.001, standardized coefficient β=-0.42). Conclusions In a population of healthy individuals GWI emerged as the only independent correlate of the VAC ratio derived from conventional echocardiography. Both GWI and VAC ratio were age related. Our results suggest that VAC ratio and GWI are complementary in their ability to characterize the complex interplay between myocardial function and arterial system. The added value of GWI in this role deserves further evaluation. Correlation between GWI and VAC ratio Univariate correlates of the VAC ratio

Pressure-volume analysis by three-dimensional echocardiography: a novel and superior method to predict response following cardiac resynchronization therapy

Abstract Introduction Long-term response to cardiac resynchronization therapy (CRT) is primarily assessed by 2D echocardiography. The combination of 3D echocardiography and left ventricular (LV) pressure curve estimation allows for pressure-volume (PV) analysis and LV work efficiency (LVWE) estimation which may be superior to today’s methods. Aim To investigate if PV-analysis by 3D echocardiography is superior to 2D volumes at predicting long-term survival in CRT. Methods In a recent prospective multicenter study, non-invasive PV-analysis (n=106) and 2D volume analysis by biplane Simpson’s method (n=195) were performed, before and 6 months after CRT. The LV pressure curve was estimated by aligning a reference pressure curve with mitral and aortic valve events obtained from echocardiography. The amplitude of the curve was adjusted to brachial systolic cuff pressure and combined with 3D volumes for PV-analysis. As shown in figure 1, LVWE was calculated as the ratio of estimated stroke work (red area) to total mechanical energy (red + blue areas). The cutoff value for change in LV end-systolic volume (ESV) was set at 15% and at >35% for LVWE using Receiver Operator Curve analysis. Volumetric non-responders were subdivided into response based on LVWE. Results After 6±2 years follow-up, 47 (23%) patients had died. Relative change in 3D and 2D LV ESV showed similar ability to predict long-term all-cause mortality (log rank p<0.001 for both) (Figure 2). However, LVWE identified patients with a positive effect of CRT who were volumetric non-responders. These patients had similar outcomes as volumetric responders (HR 1.91, 95% CI: 0.54-6.81) (Figure 3). LVWE also identified non-responders with particularly adverse outcomes (HR 3.46, 95% CI: 1.32-9.10 vs volumetric non-response and LVWE >35%). Conclusions PV-analysis by 3D-echoardiography identifies a new group of patients who respond to CRT without a 15% reduction in ESV who have similar outcomes to volumetric responders. In our data, 3D echocardiography was superior to 2D volumes at predicting long-term all-cause mortality after CRT. LV work efficiency before and after CRT LV work efficiency and survival

Non-invasive assessment of arterial elastance using three-dimensional echocardiography: an accurate alternative to invasive methods

Abstract Introduction Assessing arterial elastance (Ea) is crucial for understanding vascular properties and managing conditions such as hypertension, heart failure, and valvular heart disease. While invasive pressure-volume (PV) analysis provides precise measurements, the procedures involved pose significant risks and limitations. Three-dimensional (3D) echocardiography, combined with non-invasive LV pressure curve estimation, however, offers a highly accurate method for generating non-invasive PV-loops. Thus, this approach has the potential to provide a safe and widely accessible means of assessing Ea. Aim Validate non-invasive Ea by PV analysis using 3D echocardiography, comparing it to gold-standard Ea derived from invasive measurements. Methods In 10 open-chest canines, invasive pressure was measured using a micromanometer, and volume determined from subendocardial piezoelectric crystals, using a three-axis ellipsoid model (Figure 1). Echocardiography provided non-invasive 3D LV volumes and valve event timings. The LV pressure curve was estimated by adjusting a reference curve to the valve events and measured peak LV pressure, which in clinical practice would be approximated as systolic brachial cuff pressure. Arterial elastance (Ea) was defined as the absolute slope of the line from volume axis interception at end-diastolic volume to the point on the PV-loop in the upper left quadrant with the longest normalized distance from the loop center. Recordings were performed at baseline and during aortic constriction. Results Panel A in Figure 2 illustrates how tightly non-invasive (dotted lines) followed invasive (solid lines) pressure-volume curves both during baseline (left) and aortic constriction (right) in a representative experiment. As can be seen, this resulted in very similar Ea. Panel B shows pooled data from all experiments, demonstrating that indeed, the non-invasive method captured similar changes in Ea during aortic constriction compared to the invasive method. Furthermore, as shown in panel C, there was an excellent correlation (r = 0.91, p < 0.0001) and good agreement (mean difference 0.3, SD 0.3) between the non-invasive and invasive Ea. Conclusions Three-dimensional echocardiography provides an accurate and non-invasive method for assessing arterial elastance, with excellent agreement with gold standard invasive method. Ultrasound crystals placement Invasive vs non-invasive Ea

Patterns of left ventricular remodeling according to the type of sport in a cohort of elite athletes assessed by speckle tracking echocardiography

Abstract Background Athletic training is associated with hemodynamic demands leading to physiological cardiac changes referred to as athlete’s heart. Whilst some studies support the hypothesis with predicted eccentric left ventricular hypertrophy (LVH) from endurance training, data confirming concentric-type effects of resistance training are inconsistent. Also, whether specific geometric adaptations are associated with specific changes of LV myocardial performance is undefined. Purpose To assess patterns of LV remodeling in relation to the type of sport, using speckle tracking echocardiography (STE) in a cohort of elite athletes (EA). Methods 132 EA (23±5 years) referred for resting echocardiography during annual check-up were prospectively enrolled.They were involved in competitive sports for >10 hours/week for over 3 years and had no history of cardiac/non-cardiac disease or sudden cardiac death. A control group of 15 healthy volunteers (25±3 years), either sedentary or engaged in <6 h of non-competitive training/week, was enrolled. An echocardiogram was performed in all subjects. Global myocardial work (MW) indices - work index (GWI), constructive work (GCW), work efficiency (GWE) and wasted work (GWW)- were calculated using a software able to construct a noninvasive LV pressure-strain loop based on STE-derived global longitudinal strain (GLS) and LV pressure from systolic cuff pressure. Analysis was performed by an experienced investigator blinded to the sport history of each subject. Results Four subgroups of EA were defined according to the sports disciplines: power (n=27), endurance (n=30), mixed (n=62) and skill (n=13). Mean values of LV volumes, wall thickness and mass were significantly higher in EA compared with controls. Normal LV geometry was present in >50% of EA in each group and >70% of power and skill EA. LVH was more prevalent in endurance (23.3%) and mixed (19.4%) as compared to skill (7.7%) and power (7.4%) EA. Eccentric hypertrophy was found only in endurance and mixed EA (<15% each group). Including age, BSA, gender, sport discipline, duration and intensity of training in binary logistic regression to predict LVH, increasing age was the only significant predictor (p=0.01). Conventional and advanced parameters of LV systolic and diastolic function were within normal range in all subjects. The one-way ANOVA revealed no significant differences between groups of EA and controls regarding mean values of GLS, LV ejection fraction and MW indices. However, among EA, endurance EA exhibited the highest values of GCW(2075±228 mmHg%), GWI(1767±222 mmHg%) and GWE(95.5±1.7%) and lowest GWW(76±35 mmHg%) with statistic significance for GWW(p=0.03) and marginally for GWE(p=0.05). Conclusion In our study, the type of sport was not related to the presence of LVH. The most significant LV remodeling was observed in EA, as expected, associated with a resting myocardial work profile characterized by highest values of GWI, GCW and GWE and lowest GWW. MW parameters and the type of sport

Usefulness of echocardiographic parameters of myocardial work in the evaluation of left ventricular function in patients with severe aortic valve stenosis undergoing transcatheter aortic valve impla

Abstract Background Myocardial work (MW) is a new echocardiographic parameter used in the assessment of cardiac energy expenditure. Purpose The aim of the current study was to evaluate changes in left ventricular MW parameters in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Methods One hundred and thirty five consecutive patients who underwent TAVI at one center were evaluated before and after procedure by transthoracic echocardiography (TTE) with the assessment of MW indices: global constructive work (GCW), global wasted work (GWW), global work index (GWI) and global work efficiency (GWE). Results The comparison of MW parameters before and on average after 5.9 days after TAVI showed a significant increase in GCW: 1314,48± 487,53 vs 1438,22 ± 468,86 (p<0,001), GWW: 238,82 ± 160,67 vs 258,84 ± 145,09 (p= 0,045) and GWI: 966,45 ± 456,06 vs 1045,16 ± 428,68 and no significant change in GWE: 81,55 ± 10,46 vs 82,47 ± 7,75 (p=0,401). The increase in GCW and GWI parameters after TAVI strongly correlated with left ventricular ejection fraction (LVEF) and pressure aortic gradient (PGA) before the procedure. A significant increase in GWE was observed in patients with LVEF <30% (p=0,043). Conclusions Echocardiographic assessment of myocardial work parameters is a valuable method of documenting hemodynamic changes in patients with severe aortic stenosis before and after TAVI. Long-term left ventricular overload in patients with aortic stenosis results in a global decrease of myocardial work parameters, therefore, rapid decompression increases the effective work of the heart.

Maladaptive remodeling reduces survival in patients with moderate aortic stenosis and preserved ejection fraction

Abstract Background Aortic valve stenosis (AS) is a common cause of left ventricular (LV) pressure overload and subsequent hypertrophy and diastolic dysfunction. The extent of LV hypertrophy does not necessarily correlate with the severity of valve stenosis and excessive LV remodeling can be seen in moderate AS. Therefore aortic stenosis is the disease of valve and myocardium. Left ventricular hypertrophy (LVH) with different geometric patterns is associated with adverse prognosis, The concept of staging AS disease rather than merely classifying AS based on hemodynamic severity seems more appropriate. Current guidelines do not address whether aortic valve replacement should be recommended in patients with moderate aortic valve stenosis regardless of the presence of LV dysfunction. Purpose This study aimed to investigate differences in left ventricular remodeling and its impact on survival in patients with unequivocally moderate aortic stenosis and preserved LV ejection fraction. Methods We retrospectively analyzed 182 unequivocally moderate AS patients (57% were male, age was 70±9), who underwent transthoracic echocardiography from March 2018 to November 2021. AS severity was defined by specific threshold values peak velocity 3-4 m/sec, an MPG 20-40 mmHg and an AVA 1-1.5 cm. All values were concordant and suggested moderate AS. All patients were in sinus rhythm and with LV ejection fraction >50%. We calculated the LV mass index (LVMI) and ventricular geometry was assessed with a relative wall thickness (RWT). Left ventricular hypertrophy (LVH) was defined as LV mass index >95g/m2 in women and >115g/m2 in men and was defined as concentric when associated with a RWT>0.42 and eccentric when RWT was ≤0.42. Concentric remodeling was defined as normal LVM index and increased RWT. The follow-up assessment in December 2023 ascertained vital status and data on aortic valve replacement (AVR). Results LVH was present in 91 patients (50%). Eccentric LVH was present in 49 (27%), concentric LVH in 42 (23%), and concentric remodeling in 27 (15%). During a median 41 months follow-up, 49 (27%) deaths occurred. 32 (18%) patients undervent AVR. As expected, LV hypetrophy was associated with all-cause mortality (HR 2.556; CI: 1.007-6.448; p = 0.048), and if concentric hypertrophy was present mortality was even higher (HR 3.736; CI: 1.553-8.992; p = 0.003) AVR had a non-statistically significant protective effect (HR 0.654; CI: 0.193 -2.220; p = 0.496). Conclusion Maladaptive remodeling is associated with worse outcomes in patients with moderate AS. RWT is important for identification of abnormal geometry. Further studies investigating the adequate timing of AVR in patients with moderate AS with maladaptive LV response are needed.

Aorto-mitral angle: an emerging indicator for successful alcohol septal ablation in hypertrophic obstructive cardiomyopathy - a pilot study

Abstract Background Approximately 10-20% of patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA) exhibit a suboptimal response, despite accurate targeting of the septal artery. This suboptimal response may be due to structural and functional factors related to the mitral valve and left ventricular (LV) dimensions. Currently, there is a lack of specific parameters or cutoffs to predict ASA success. The aorto-mitral angle is crucial for predicting systolic anterior motion (SAM) in mitral valve repair surgery, but its relationship with ASA outcomes remains underexplored. Purpose This study aims to investigate the relationship between aorto-mitral angle values and the success of alcohol septal ablation, and to assess the impact of this parameter on ASA outcomes. Methods The study retrospectively included 23 HOCM patients who underwent ASA in our clinic, with data collected from thorough evaluations conducted before and at least six months after the procedure. The left ventricular outflow tract pressure gradient (LVOT PG) and other standard parameters were measured using transthoracic echocardiography. The aorto-mitral angle was assessed through three-dimensional data acquisition during transoesophageal echocardiography, analyzed offline using specific software (zoom 3D of the mitral valve, MVQ). Results Nineteen patients experienced successful ASA, defined as a >50% reduction in LVOT PG compared to baseline, while four patients had suboptimal results. There were no significant differences in baseline LV dimensions, LVOT PG, age, or comorbidities between the groups. The aorto-mitral angle was significantly higher in patients with successful ASA (138.21 ± 7.6 versus 115 ± 9.2 degrees, p<0.001). This angle correlated with the percentage decrease in LVOT PG (R = 0.59, p = 0.02), though the correlation with the absolute decrease was not statistically significant (R = 0.38, p = 0.06). After further validation, the aorto-mitral angle may be useful for predicting ASA success (logistic regression odds ratio 1.37, 95% confidence interval (1.01, 1.86), p = 0.04). Additionally, significant differences were found between redundant anterior mitral leaflet (AML) length, anterior displacement of the coaptation point, and ASA success in this cohort (p = 0.04 for both). Conclusion The aorto-mitral angle appears to play a role in the obstruction mechanism of HOCM and could serve as a valuable predictor for ASA success. These findings may prompt further investigation and potential inclusion of this parameter in a prediction model alongside other mitral valve and LV size parameters.

What happens to myocardial work after transcatheter aortic valve replacement?

Abstract Background Novel echocardiographic speckle-tracking techniques such as global longitudinal strain (GLS) and myocardial work (MW) have been used in many cardiac conditions for myocardial functional assessment. In severe aortic stenosis (SAS) this evaluation is more challenging since left ventricular (LV) systolic pressure (SP) does not equal non-invasive systolic pressure (NISP) owing to the fixed obstruction of a stenotic valve. Few studies have evaluated the immediate impact of transcatheter aortic valve replacement (TAVR) in patients with SAS on GLS and MW parameters. Aim To assess differences in GLS and MW parameters values, pre- and post-TAVR, in patients with SAS. Methods One-single center retrospective analysis of consecutive patients with SAS submitted to TAVR, between January 2018 and December 2021, who performed transthoracic echocardiography (TTE) bfore and after the procedure (within the same hospital admission). NISP was determined at TTE performance. For pre-TAVR assessment, corrected SP by adding the mean aortic gradient was introduced in the software for MW parameters calculations, namely global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). Continuous variables were assessed for normality using Shapiro-Wilk test. Normal variables were represented as mean and standard deviation (SD) and compared using a paired-sample t-test. Non-normal variables were represented as median and interquartile range (IQR) and compared using a Wilcoxon-Signed rank test. Statistical significance was defined as two-sided p value < 0.05. All statistical analysis were done with JASP (version 0.16.0.0). Results 50 patients entered the primary analysis. Mean age was 82 years and 56% were female sex. Before TAVR, mean aortic gradient was 49 ± 15 mmHg, mean aortic valve area was 0.76 ± 0.22 cm2 and LV ejection fraction was 52 ± 11%. Table 1 represents the mean GLS and MW parameters values pre- and post-TAVR from our study population. Patients had significant lower values of GWI (1764.4 ± 704.9 vs. 1197 ± 372.6, p < 0.001) and GCW (2309.5 ± 810.9 vs. 1627.8 ± 488.5, p < 0.001) post-TAVR when compared with the pre-TAVR values. There were no significant differences in GLS (p=0.837), GWW (p=0.055) and GWE (P=0.438) values pre- and post-TAVR. Conclusion In our study population, GLS was impaired in patients with SAS and it remained identical after TAVR, suggesting un underlying myopathy that does not reverse immediately after the procedure. Furthermore, MW as assessed by GWI was significantly reduced after TAVR, which may reflect the reduced workload needed after the procedure due to acute afterload reduction. Further studies with longer follow-up are needed to acess the long term impact of TAVR in MW. TAVR MW

Left ventricular pressure-strain-volume-loop and myocardial work patterns in asymptomatic severe aortic regurgitation with early disease decompensation

Abstract Background Severe aortic regurgitation (AR) is associated with left ventricular (LV) pressure and volume overload, leading to irreversible myocardial damage often before the onset of guidelines triggers for aortic valve surgery. Therefore, the development of sensitive imaging markers to detect the early impact of pressure-volume overload imposed by AR on LV geometry and function is needed. Aim To describe patterns of LV pressure-strain-volume loops, their components and myocardial work in asymptomatic patients with significant AR and preserved LV ejection fraction with early disease progression. Methods This multicenter study consisted of 95 consecutive patients (84.1% male, 45±14 years) with asymptomatic significant AR, in sinus rhythm, and preserved LV ejection fraction (EF) >50%, who did not have any indication for aortic valve surgery as per current guidelines. Comprehensive echocardiography was analyzed by an experienced operator blinded to clinical outcome. Pressure-strain-volume loops (PSVL), their components, and myocardial work were analyzed using customized software. Results During a median follow-up of 1375 [interquartile range 1041-1783] days, a total of 34 (36%) patients developed the class I indication for aortic valve surgery, i.e. either symptoms or LV dysfunction (AVsurg group). At baseline, LVEF (64±5% vs. 64±7%;p=0.748), global longitudinal strain (-17.6 ± -2.4% vs. -18.5 ± -2.4%; p=0.112), global myocardial work index (1963±429 vs.1900±340 mmHg%; p=0.429) or global constructive work (2371±495 vs. 2287±368 mmHg%; p=0.390) did not differ significantly between groups. In contrast, global wasted work was significantly higher (149[90-204] vs.106[80-152] mmHg%; p=0.031) in the Avsurg group compared to the patients without progression for AV surgery indication (CON group). Moreover, the AVsurg group showed a larger PSVL area than the CON group probability due to the larger strain-volume (234 [129-380] vs.155 [88-216] %mL; p=0.021) and pressure-volume (12504 [9318- 15073] vs. 10192 [8004-11918] mmHg.mL; p=0.002) component, while the pressure-strain loop was similar between groups (Figure 1). Conclusions Non-invasive pressure-strain-volume loop reflects early changes in LV geometry and function due to chronic pressure-volume overload in significant AR. Patients with early disease decompensation show larger PSVL than stable individuals. The clinical utility of this index needs to be investigated in future studies. Figure 1