Elevated Left Ventricular End-diastolic Pressure Research Articles

Coronary microvascular dysfunction in heart failure: observations from the MICRO registry

Abstract Background Heart failure (HF) is one of the leading causes of hospitalization in the elderly. Coronary microvascular dysfunction (CMD), among other risk factors, is linked to the pathogenesis and clinical manifestations of HF. Purpose This abstract aims to summarize key findings from a comprehensive analysis of CMD in subgroups of HF, shedding light on its association with hemodynamic parameters. Methods Patients experiencing recurrent angina (CCS II-IV) and no relevant epicardial stenosis were enrolled in a prospective registry (MICRO). Epicardial and microvascular responses (pressure, resistance and flow) were assessed at rest and during adenosine and acetylcholine testing. The impact of an elevated left ventricular end-diastolic pressure (LVEDP) in the absence of clinical signs of HF was also investigated. Results Overall, 188 patients (63% (118) women, mean age 65±11 years) with angina and no epicardial stenosis were enrolled. Patients with HF (n=26) displayed lower hyperemic flow in response to endothelium-independent adenosine (5.2±3.1 vs. 7.3±4.4; P=0.004), lower coronary flow reserve (2.9±1.5 vs. 4.4±1.1; P<0.001) and microvascular resistance reserve (3.3±2.1 vs. 5.2±2.7; P<0.001), and increased microvascular resistance during adenosine-induced hyperemia (25±21 vs. 17±11; P=0.045). An increased LVEDP without clinical signs of HF was not associated with a lower coronary flow reserve (4.3±1.9 vs. 2.6±1.2; P=0.006) or microvascular resistance reserve (4.9±2.1 vs. 2.8±1.7; P=0.004). Microvascular resistance during acetylcholine (endothelium-dependent)-induced hyperemia was lower in HF patients (36.2±23.5 vs. 57.4±37.8; P=0.018). Conclusion(s) Patients with heart failure displayed signs of impaired microvascular endothelium-independent responses while endothelium-dependent reactivity appears to be maintained. An elevated LVEDP without clinical HF was not associated with impaired coronary microvascular function.

Incorporating intrathoracic pressure fluctuation can improve noninvasive prediction of left ventricular end-diastolic pressure

Abstract Introduction Heart failure (HF) is a leading cause of mortality and morbidity, with a prevalence above 10% in elderly population (1). Left ventricular end-diastolic pressure (LVEDP) is a known indicator for all types of HF. An invasive pressure catheter is the gold standard for measuring LVEDP (2). However, it involves an in-hospital procedure and is costly, which limits the accessibility. A noninvasive strategy would improve early diagnosis and reduce the burden on secondary care. Several noninvasive classifiers are able to detect elevated LVEDP (3-5), with some receiving FDA clearance (6). While beneficial for triaging patients, these classifiers cannot quantify the severity and track disease progression. Developing a noninvasive LVEDP regression model requires accounting for respiration dynamics. Even invasively, the dynamics make measuring LVEDP challenging. This study uses an error metric from ANSI/AAMI/ISO 81060-2:2019 (AAMI) (7) to evaluate the effect of respiration on noninvasive LVEDP regression results. Methods The dataset (147 patients, 21+ yrs old, mean 65 ± 10 yrs; 68% male) consisted of patients referred for nonemergent left heart catheterisation inclusive of direct assessment of LVEDP. Noninvasive data was collected by a modified brachial cuff with a single-lead electrocardiogram (ECG). Invasive data was acquired using a Millar pressure catheter. LVEDP was derived based on the time of the R-wave of the ECG (8). For each patient, 40 secs of noninvasive data with synchronised catheter signals were analysed to build an LVEDP regression model. Inputs were generated from the ECG and brachial pressure waves based on fiducials identified in both signals. Leave-one-subject-out cross-validation (LOSO CV) was used to train and test the algorithm. The impact of respirophasic variation on the model was analysed by comparing the prediction with the mean LVEDP and the range of the mean ± standard deviation (std) (i.e. AAMI error metric). Results The results, evaluated using Bland-Altman and correlation analysis, showed a decrease in the mean absolute error (MAE) from 3.6 mmHg to 1.4 mmHg, the std from 4.9 mmHg to 3.0 mmHg, and the correlation (r) from 0.57 to 0.77 when incorporating intrathoracic pressure swings (Fig.1 and Fig.2). A Levene test on the residuals of the two error determinations showed a significant difference (p-value < 0.01). Conclusion Irrespective of the error metric, the model performance meets the AAMI standard for blood pressure (BP) measurement. Moreover, when respiratory motion is included, agreement with invasive LVEDP improves considerably. From a clinical perspective, this emphasises the importance of targeting end-expiratory LVEDP. With respect to noninvasive BP measurement, it suggests that both brachial BP evaluation and LVEDP prediction should attempt to quantify fluctuations. While the challenge remains, these results indicate that noninvasive LVEDP prediction could be realised in the near future.Fig.1 Prediction vs mean LVEDP.Fig. 2 Prediction vs mean +/- std.

Electrocardiographic Findings in Patients with Severe COVID-19: Characterisation and Clinical Correlations

In a prospective study of 200 COVID-19 patients, categorised into mild symptoms (category A; n=39), mild symptoms with cardiopulmonary comorbidities (category B; n=68) and severe symptoms with haemodynamic compromise (category C), category C showed higher incidences of left axis deviations, left atrial enlargement, prolonged QRS, elevated left ventricular amplitude, poor R wave progression and T inversion in V1–V6. A novel marker, rS complex – R/S ratio >1 in lead III, was noted. Univariate analysis revealed left atrial enlargement, left axis deviation, left ventricular amplitude and poor R wave progression as mortality predictors. Multivariate analysis identified age and left atrial enlargement as independent predictors. These findings suggest possible elevated left ventricular end-diastolic pressure, which will help in categorising disease severity and predicting outcomes.

Artificial intelligence machine learning based evaluation of elevated left ventricular end-diastolic pressure: a Cleveland Clinic cohort study

Artificial intelligence machine learning based evaluation of elevated left ventricular end-diastolic pressure: a Cleveland Clinic cohort study

A prospective analysis of the correlation between ultrasonic B-lines, cardiac tissue doppler signals and left ventricular end-diastolic pressure in patients with severe aortic stenosis

BackgroundThe development of heart failure is a turning point in the natural course of aortic stenosis (AS). Pulmonary oedema and elevated left ventricular pressure (LVP) are cardinal features of heart failure. Evaluating pulmonary oedema by lung ultrasound involves taking the upper hand with a bedside noninvasive tool that may reflect LVP.AimWe sought to assess the correlation between sonographic pulmonary congestion, invasive LV pre-A pressure, and echocardiographic LV end-diastolic pressure (LVEDP) in symptomatic AS patients receiving transcatheter aortic valve replacement.MethodsForty-eight consecutive patients with severe AS and planned transcatheter aortic valve implantation (TAVI) were enrolled. LVEDP was estimated to be normal or elevated using the ASE/EACVI algorithm and transmitral Doppler indices, the E/A ratio, the E/e′, and the left atrial volume index. Invasive LV pre-A pressure was used as a reference, with > 12 mm Hg defined as elevated.ResultsForty-eight patients (25 women (52%), mean age 75 years, standard deviation (SD) ± 7.7 years) were enrolled in the study. We detected severe B-lines (≥ 30) in 13 (27%) patients and moderate B-lines (15–30) in 33 (68.6%) patients. The number of B-lines increased significantly with the severity of New York Heart Association (NYHA) functional classes (Fig. 1). The B-line count was 14 ± 13 in NYHA class I patients, 20 ± 20 in class II patients, and 44 ± 35 in class III patients (p < 0.05, rho = 0.384). The number of B-lines was correlated with the E/E’ ratio (R = 0.664, p < 0.0001) and the proBNP level (R = 0. 882, p < 0.008). We found no significant correlation with the LVEDP or LVEF. The LVEDP correlated well with the E/E’ ratio (R = 0.491, p < 0.001) but not at all with E/A, DT, or LAVI. All patients had an elevated LVEDP > 12, with a mean pressure of 26 mmHg, a minimum of 13 mmHg, and a maximum of 45 mmHg, with an SD of 7.85.ConclusionAssessing lung ultrasonic B-lines is a straightforward and practical approach to identifying pulmonary oedema in AS patients. The number of B-lines correlated with the E/E’ ratio and the functional status of patients but did not correlate with invasive LVEDP or LVEF. All patients had elevated LVEDP that correlated with E/E’.

Abstract Mo101: 3-Mercaptopyruvate Sulfurtransferase is a Critical Regulator of Branched-Chain Amino Acid Catabolism in Cardiometabolic HFpEF

Background: Heart failure with preserved ejection fraction (HFpEF) is among the leading causes of cardiovascular mortality and morbidity. Recent multi-omics data sets underscore severely impaired branched-chain amino acid (BCAA) catabolism in the failing hearts of HFpEF patients. 3-mercaptopyruvate sulfurtransferase (3-MST) is a mitochondrial hydrogen sulfide (H 2 S) synthase that regulates mitochondrial biogenesis, function, and substrate metabolism. Research Questions and Goals: In the current study, we aimed to elucidate the role of 3-MST in myocardial BCAA catabolism in cardiometabolic HFpEF. Methods: 3-MST knockout or wild-type (WT) mice were subjected to control or L-NAME and high fat diet - induced HFpEF. Echocardiographic measurements, invasive hemodynamic assessment, and exercise capacity testing were conducted to determine HFpEF severity. Metabolomic analysis was performed to study BCAA catabolism. Additionally, a H 2 S donor, SG1002 was administered to increase H 2 S bioavailability in the setting of 3-MST deficiency and HFpEF. Results: We observed progressive deterioration in left ventricular (LV) diastolic function and exercise performance from mice subjected to HFpEF. Genetic ablation of 3-MST further-exacerbated HFpEF severity as evidenced by significantly increased E/e’ ratio, elevated LV end-diastolic pressure, and reduced exercise performance. Metabolomic analysis revealed pathological accumulation of intermediate metabolites of BCAA in the HFpEF hearts, suggesting a major derangement in myocardial BCAA catabolism. 3-MST KO hearts exhibited further BCAA catabolic defects as compared to those from WT. Importantly, H 2 S donor treatment significantly attenuated BCAA catabolic defect and alleviated HFpEF severity in both WT and 3-MST KO HFpEF mice. Conclusion: Our results demonstrate that deficiency of 3-MST impairs myocardial BCAA catabolism, which results in exacerbated HFpEF severity in a “two-Hit” mouse model of HFpEF. These data suggest 3-MST is critically involved in physiological substrate metabolism within the mitochondria and exerts beneficial effects in HFpEF. Future experiments are underway to delineate the mechanisms by which 3-MST regulates BCAA catabolism.

Abstract We105: cBIN1 Gene Therapy Improves Left Ventricular Filling Pressure in a Canine Model of Ischemic Dilated Cardiomyopathy

Introduction: In heart failure patients, increased left ventricular end diastolic pressure (LVEDP) is pathognomonic of myocardial dysfunction. Previously, we presented that gene therapy with exogeneous cardiac bridging integrator 1 (cBIN1), a membrane scaffolding protein that organizes T-tubule microdomains and is decreased in failing hearts, recovers systolic function in a canine model of chronic ischemic dilated cardiomyopathy (IDCM). The effect of catheter-based delivery of cBIN1 gene therapy on increased LVEDP is unclear. Hypothesis: We tested the hypothesis that cBIN1 gene therapy improves LVEDP in a canine model of IDCM. Methods: Twelve healthy dogs (30±2 kg) underwent left anterior descending artery ligation and developed IDCM with LVEF &lt;40% and NT-proBNP &gt;900 pmol/L over 3–4 months. Animals received a single application at 20 subendocardial LV sites of either AAV9-GFP (control, n=6) or AAV9-cBIN1 (n=6) using a MyoStar catheter-based injection. Pressure-volume loops were acquired in vivo, including measurement of LVEDP, end-systolic pressure-volume relation (ESPVR), isovolumic relaxation time (IVRT) and isovolumetric contraction time (IVCT). Measurements were performed on the day prior to administering the therapy ( pre-therapy ) and 5–8 weeks post-intramyocardial injection ( post-therapy ). For statistics, student t-test was used, and p&lt;0.05 refers as significant. Results are reported as mean±SD. Results: In AAV9-GFP control-treated dogs, compared with pre-therapy, post-therapy LVEDP elevated significantly (13±1 vs. 17±1 mmHg, p=0.002, Figure A ), whereas in the cBIN1-treated cohort, elevated LVEDP improved significantly (13±4 vs. 11±3 mmHg, p=0.042). With control therapy, ESPVR exhibited a significant decrease in contractility (1.40±0.44 vs. 1.81±0.49 mmHg/mL, p=0.001, Figure B ), whereas cBIN1 therapy caused a substantial improvement in ESPVR (1.54±0.71 vs. 1.34±0.43 mmHg/mL, p=0.022, Figure B ). At the post-therapy time-point, compared with control therapy, cBIN1 therapy improved IVRT (96±10 vs. 72±8 ms, p&lt;0.001, Figure C ) and IVCT (49±4 vs. 40±3 ms, p=0.009, Figure D ). Conclusion: cBIN1 gene therapy reduces elevated LV filling pressure and improves overall hemodynamics in a canine model of chronic IDCM.

Detecting elevated left ventricular end diastolic pressure from simultaneously measured femoral pressure waveform and electrocardiogram

Objective. Instantaneous, non-invasive evaluation of left ventricular end-diastolic pressure (LVEDP) would have significant value in the diagnosis and treatment of heart failure. A new approach called cardiac triangle mapping (CTM) has been recently proposed, which can provide a non-invasive estimate of LVEDP. We hypothesized that a hybrid machine-learning (ML) method based on CTM can instantaneously identify an elevated LVEDP using simultaneously measured femoral pressure waveform and electrocardiogram (ECG). Approach. We studied 46 patients (Age: 39–90 (66.4 ± 9.9), BMI: 20.2–36.8 (27.6 ± 4.1), 12 females) scheduled for clinical left heart catheterizations or coronary angiograms at University of Southern California Keck Medical Center. Exclusion criteria included severe mitral/aortic valve disease; severe carotid stenosis; aortic abnormalities; ventricular paced rhythm; left bundle branch and anterior fascicular blocks; interventricular conduction delay; and atrial fibrillation. Invasive LVEDP and pressure waveforms at the iliac bifurcation were measured using transducer-tipped Millar catheters with simultaneous ECG. LVEDP range was 9.3–40.5 mmHg. LVEDP = 18 mmHg was used as cutoff. Random forest (RF) classifiers were trained using data from 36 patients and blindly tested on 10 patients. Main results. Our proposed ML classifier models accurately predict true LVEDP classes using appropriate physics-based features, where the most accurate demonstrates 100.0% (elevated) and 80.0% (normal) success in predicting true LVEDP classes on blind data. Significance. We demonstrated that physics-based ML models can instantaneously classify LVEDP using information from femoral waveforms and ECGs. Although an invasive validation, the required ML inputs can be potentially obtained non-invasively.

Correlation of left atrial strain with invasively measured left ventricular end-diastolic pressure; determining LA strain cut-off value.

Left atrium longitudinal strain (LAS) with speckle tracking method has been proposed as a non-invasive method for the assessment of left ventricular filling pressure and diastolic dysfunction. This study aimed to investigate left atrial strain compared to invasively measured left ventricular filling pressure. All Patients candidates for coronary angiography were consecutively recruited. LAS measured by transthoracic echocardiography. Left ventricular end-diastolic pressure (LVEDP) pressure was invasively measured. Current echocardiographic modalities for diastolic function evaluated. A total of 125 people were included. 45 patients had preserved ejection fraction (EF ≥ 50%) and 85 patients had reduced EF (EF < 50%) and compared two groups. LVEDP was significantly higher in reduced EF compared to preserved EF (p-value < 0.001). LA-reservoir and LA-booster strains were significantly lower in patients with reduced EF compared to preserved EF (p-value = 0.008, mean Reservoir = 16.4% ± 6.4, mean Reservoir = 19.5% ± 5.6, respectively) and (p-value = 0.009, mean Booster = 9.09% ± 4.0, mean Booster =11. 9% ± 4.3, respectively). LA 4ch-reservoir strain <14.4%, and LA 2ch-reservoir strain <14.1% were related to LVEDP≥20 mmHg (sensitivity 63.5% and specificity 75%) (sensitivity 77.9% and specificity of 60%) respectively. LAS is significantly lower in patients with elevated LVEDP (≥ 20mmHg). LAS is significantly lower in patients with reduced EF. Both LA-reservoir and LA-booster strains have a significant relation to predicting LVFP but LA-reservoir strain is more accurate. The mean LA-reservoir strain less than 12.4% is associated with LVEDP ≥ 20mmHg.

Improved Interpretation of Pulmonary Artery Wedge Pressures through Left Atrial Volumetry-A Cardiac Magnetic Resonance Imaging Study.

The pulmonary artery wedge pressure (PAWP) is regarded as a reliable indicator of left ventricular end-diastolic pressure (LVEDP), but this association is weaker in patients with left-sided heart disease (LHD). We compared morphological differences in cardiac magnetic resonance imaging (CMR) in patients with heart failure (HF) and a reduced left ventricular ejection fraction (LVEF), with or without elevation of PAWP or LVEDP. We retrospectively identified 121 patients with LVEF < 50% who had undergone right heart catheterization (RHC) and CMR. LVEDP data were available for 75 patients. The mean age of the study sample was 63 ± 14 years, the mean LVEF was 32 ± 10%, and 72% were men. About 53% of the patients had an elevated PAWP (>15 mmHg). In multivariable logistic regression analysis, NT-proBNP, left atrial ejection fraction (LAEF), and LV end-systolic volume index independently predicted an elevated PAWP. Of the 75 patients with available LVEDP data, 79% had an elevated LVEDP, and 70% had concomitant PAWP elevation. By contrast, all but one patient with elevated PAWP and half of the patients with normal PAWP had concomitant LVEDP elevation. The Bland-Altman plot revealed a systematic bias of +5.0 mmHg between LVEDP and PAWP. Notably, LAEF was the only CMR variable that differed significantly between patients with elevated LVEDP and a PAWP ≤ or >15 mmHg. In patients with LVEF < 50%, a normal PAWP did not reliably exclude LHD, and an elevated LVEDP was more frequent than an elevated PAWP. LAEF was the most relevant determinant of an increased PAWP, suggesting that a preserved LAEF in LHD may protect against backward failure into the lungs and the subsequent increase in pulmonary pressure.

Case report of increased left ventricular end-diastolic pressure with pulsatile left ventricular assist device

Abstract Background Left ventricular assist devices (LVADs) are increasingly utilized in cardiogenic shock and high-risk percutaneous coronary interventions (PCIs). These devices aspirate and expel blood from the left ventricle (LV) into the aorta, consequently reducing left ventricular end-diastolic pressure (LVEDP). We report a case of unexpected LVEDP rise under LV-to-aorta LVAD in the context of transcatheter aortic valve implantation (TAVI) and concomitant multi-vessel PCI. Case summary A patient with acute heart failure, severely depressed systolic LV function, severe aortic stenosis, and multi-vessel coronary artery disease underwent TAVI and concomitant PCI under pulsatile LVAD. Notably, the patient experienced unexpected shortness of breath and elevated LVEDP while under LVAD, which normalized immediately upon LVAD removal. Discussion Pulsatile LVAD enhances cardiac output by providing pulsatile support through a percutaneous bi-directional flow catheter. Despite expectations of reduced LVEDP and improved myocardial oxygen supply under LVAD support, we observed high LVEDP and clinical complaints of shortness of breath following TAVI and multi-vessel PCI. This case illustrates that an LVAD across the aortic valve may immobilize aortic leaflets and generate acute aortic regurgitation.

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

The Association and Utility of Left Ventricular End-Diastolic Pressure in Predicting the Development of and in Managing Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography.

Contrast-induced nephropathy (CIN) is a significant complication in patients undergoing coronary angiography, and its development is associated with increased morbidity and mortality. Left ventricular end-diastolic pressure (LVEDP) provides one index of left heart filling status. An elevated LVEDP can reflect volume overload or abnormal diastolic function and indicates a cardiac disorder. Data on the association between an elevated LVEDP and CIN are limited and have had conflicting results. We systematically searched the databases PubMed, Embase, and Scopus for full-text articles from database inception to May 2022. Studies were included if they evaluated the association between a high LVEDP and the incidence of CIN in patients undergoing coronary angiography. The study was registered in the PROSPERO CRD42022334070. A second search in PubMed identified randomized controlled trials using LVEDP to guide fluid administration during coronary procedures. Four studies were identified that used LVEDP to classify patients into groups to determine the association between the level and the development of CIN. In these studies, 240 patients of 2441 patients (9.8%) developed CIN. One study found no association between LVEDP levels and the development of CIN. Two studies found an increased frequency of CIN in patients with elevated levels using 2 cutoff points for LVEDP, ≥20 mm Hg and >30 mm Hg. One study found that lower LVEDP levels (5-14 mm Hg) were associated with the development of CIN. Three randomized control trials used LVDEP levels to manage fluid administration in patients undergoing coronary procedures; only one study found that the use of these levels to guide fluid administration resulted in better outcomes. In patients undergoing coronary angiography, an elevated LVEDP was not consistently associated with increased risk of CIN, and using LVEDP levels to guide fluid administration during these procedures did not always improve outcomes in comparison to other protocols. The use of LVEDP levels can help classify patients with cardiac disorders but does not necessarily provide an adequate description of the hemodynamic patterns in these patients to predict or prevent CIN in patients undergoing angiography.

Echocardiographic estimation of left ventricular filling pressures in heart transplant recipients

BackgroundEchocardiographic estimation of left ventricular filling pressure in heart transplant (HTx) recipients is challenging. The ability of echocardiography to detect elevated left ventricular end-diastolic pressure (LVEDP) in HTx patients was assessed in this study.ResultsThis descriptive cross-sectional study included 39 HTx recipients who were candidates for endomyocardial biopsy as a part of their routine post-transplantation surveillance. Doppler transthoracic echocardiography was done before the procedure, and left heart catheterization was done during the endomyocardial biopsy. Thirty-nine patients (15 female, 24 male), with a mean age of 39.6 years (range 13–70), were enrolled. A strong relation was observed between lateral E/e′ and LVEDP (R = 0.64, P value < 0.001) and average E/e′ and LVEDP (R = 0.6, P value < 0.001). The best cutoff value for LVEDP prediction was the average E/e′ ≥ 6.8 with a sensitivity of 96.15% and specificity of 68.5% for the prediction of LVEDP more than or equal to 20 mmHg. Two predictive models comprising age, gender, and lateral E/e′ or average E/e′ were also proposed. A significant relationship was also found between LVEDP and left ventricular global longitudinal strain (R = − 0.31, P value < 0.01).ConclusionsLateral E/e′ was the best predictor of LVEDP. The cutoff of average E/e′ had the best validity for the estimation of LVEDP. Despite the strong observed association, echocardiographic parameters cannot be considered a surrogate for invasive LVEDP measurements when seeking information about left ventricle filling pressure on heart transplant recipients.

Association between left atrial coupling index by echocardiography and left ventricular end diastolic pressure by left ventricular catheterization

Abstract Background Left atrial volumetric/mechanical coupling index (LACi) is a novel echocardiographic parameter combining important information regarding left atrial size and function in one variable. The association between LACi and invasive pressure measurements of diastolic function has not yet been investigated. Purpose We sought to investigate the association between LACi by echocardiography and left ventricular end-diastolic pressure (LVEDP) by left ventricular catheterization. Methods Patients suspected of coronary artery disease referred for angiography had simultaneous left heart catheterization performed for invasive pressure measurements and had an echocardiogram performed. LVEDP&amp;gt;12mmHg was considered elevated. LACi was calculated as the index of LAVI (left atrial maximal volume index) and mean peak tissue velocity at late diastole measured using tissue Doppler at the base of the left ventricle. Results Forty patients were prospectively included of whom 73% were male and the mean age was 65 years. Median LACi was 2.9 (2.0, 4.1), and a total of 25 (63%) patients had elevated LVEDP. In unadjusted regression analyses, LVEDP increased with 2.3 (0.5-4.0) mmHg per 1.0 increase in LACi (p=0.013) (Figure 1, top panel). This association remained unchanged after adjusting for age and vessel disease (VD). In univariable logistic regression model, a 0.1 increase in LACi was associated with an 8% higher probability of having elevated LVEDP (OR 1.08, 95%CI (1.01-1.15), p=0.021). (Figure 1, bottom panel). These findings were consistent in multivariable analyses. Similar findings were observed in sensitivity analyses restricted to patients with normal LA size (LAVI&amp;lt;34mL, n: 34) (OR 1.10, 95%CI (1.01-1.20), p=0.027, per 0.1 increase in LACi), which also remained unchanged after adjustment for age and VD. Conclusion LACi obtained by echocardiography is associated with LVEDP and with elevated LVEDP obtained by left ventricular catheterization. Even in those with normal LA size, higher LACi can indicate elevated filling pressure.

Abstract 16544: A Multicenter Validation of a Noninvasive Brachial Cuff-ECG System for Estimation of Elevated Left Ventricular End Diastolic Pressure

Introduction: Measurement of left ventricular end diastolic pressure (LVEDP) is an established diagnostic method to evaluate all types of heart failure (HF). Invasive measurement of LVEDP requires an in-hospital procedure which limits accessibility. A noninvasive technique for detecting elevated LVEDP would significantly improve the diagnosis of HF, particularly in the outpatient setting. Herein we present the results of a multicenter study to validate a noninvasive system to detect elevated LVEDP. Methods: The Vivio System includes a modified blood pressure cuff and single lead ECG to capture brachial artery waveforms to assess preload, afterload and contractility. A model was created to identify patients with elevated LVEDP (&gt; 18mmHg). 728 patients were enrolled from 7 medical centers in the USA. All patients were referred for coronary angiography and left heart catheterization for clinical indications. A group of 321 patients with no known significant health problems were enrolled as a control group. Invasive LVEDP measurements were conducted using Millar catheters. The control group was assumed to have a LVEDP = 10 mmHg. The training dataset (n = 262, mean age 45 ± 19 yrs; 54% male) contained 101 patients with LVEDP measurements (n = 44 with LVEDP &gt; 18 mmHg) and 161 controls. The validation dataset (n = 155, mean age 46 ± 21 yrs; 62% male) contained 75 patients with LVEDP measurements (n = 40 with LVEDP &gt; 18 mmHg) and 80 controls. Results: Leave-one-out cross-validation on the training dataset yielded a sensitivity of 0.84 (95% confidence interval (CI): 0.70 - 0.93) and a specificity of 0.84 (95% CI: 0.79 - 0.89). The validation dataset showed a sensitivity of 0.80 (95% CI: 0.64 - 0.91) and a specificity of 0.83 (95% CI: 0.75 - 0.90). Figure 1 shows the overall classification performance. Conclusion: The Vivio System can accurately detect elevated LVEDP and has the potential to significantly improve early detection of HF in the outpatient setting.

Abstract 13173: Loss of ACE2 in a Diabetic Obese Setting Exacerbates Cardiovascular Dysfunction in the Setting of Gut Dysbiosis

Introduction: COVID-19 disproportionately affects older, male obese patients leading to a high prevalence of adverse outcomes. SARS-CoV-2 mediated ACE2 loss may further increase the susceptibility of these patients to adverse outcomes. Loss of ACE2 may be a causative factor in cardiovascular (CV) injury independent of primary viral-mediated injury. Methods: Male, 6-month-old, diabetic, obese db/db Ace2 -/y (double mutant, DM) mice and respective WT, Ace2 -/y , and db/db controls (n=12) were assessed for injury across the gut-heart axis. Cardiovascular parameters were evaluated by echocardiography, pressure-volume loops, and histology. Alterations in gut permeability were determined by measuring plasma peptidoglycan (PGN) levels and immunological staining of microvilli structure. Metagenomics and metatranscriptomics determined the functional and phyla alterations of the gut microbiota. Results: Loss of ACE2 in diabetic obese mice led to increased left atrium diameter (P&lt;0.001) and elevated left ventricular end-diastolic pressures (P&lt;0.05) compared to db/db mice. Cardiac remodeling was prevalent in DM hearts with increased cardiomyocyte hypertrophy (P&lt;0.001), cardiac fibrosis (P&lt;0.05), lipid accumulation (P&lt;0.01), and reactive oxygen species (ROS; P&lt;0.01) compared to db/db mice. This was associated with elevated aortic ROS (P&lt;0.001), and impaired femoral artery vasodilation (P&lt;0.001). DM mice had increased gut-blood barrier permeability, with elevated plasmalemma vesicle-associated protein-1 staining (P&lt;0.05) and plasma PGN levels (P&lt;0.01). Principal coordinates analysis of gut microbial β diversity showed distinct populations across the experimental groups (P&lt;0.05). Loss of ACE2 in db/db mice resulted in the divergence of metatranscriptomics profiles with increased expression of neutral amino acid metabolism, PGN and toxin production pathways. Conclusions: Loss of ACE2 in diabetic obese mice worsened cardiovascular dysfunction and adverse remodeling and was associated with an altered gut-cardiovascular axis characterized by elevated gut permeability and dysbiosis. Our results support worsening CV injury arising from the loss of ACE2 and may indicate a pathway of SARS-CoV-2 infection mediated CV injury.

Abstract 12374: Machine Learning-Based Evaluation of Elevated Left Ventricular End-Diastolic Pressure

Background: Left ventricular end-diastolic pressure (LVEDP) is clinically relevant due to its association with diastolic dysfunction and other outcomes. The gold-standard method of measuring LVEDP is invasive intra-cardiac catheterization. Echocardiography is routinely used for non-invasive estimation of left ventricular (LV) filling pressures; however, correlation with invasive LVEDP is variable. Goal: We sought to use machine learning (ML) algorithms to predict elevated LVEDP (&gt; 20 mmHg) using clinical, echocardiographic, and biochemical parameters. Methods: We used a cohort of 460 consecutive patients without atrial fibrillation or significant mitral valve disease who underwent transthoracic echocardiography within 24 hours of elective heart catheterization. We included patients’ clinical (e.g. age), echocardiographic (e.g. left ventricular ejection fraction), and biochemical (e.g. N-terminal brain natriuretic peptide) data. We fit logistic regression, random forest, gradient boosting, and support vector machine algorithms in a 20-iteration train-validate-test workflow and measured performance using average area under the receiver operating characteristic curve (AUROC). We also performed multi-class classification of the patients’ cardiac conditions and predicted elevated tau (&gt; 45), the gold-standard parameter for LV diastolic dysfunction. For each outcome, logistic regression weights were used to identify clinically relevant variables. Results: ML algorithms predicted LVEDP &gt; 20 mmHg with good performance (AUROC = 0.779). ML models showed excellent performance predicting elevated tau (AUROC = 0.830) and classifying a variety of cardiac conditions (AUROC = 0.837 - 0.973). We identified several clinical variables (e.g. BMI, heart rate) relevant to LVEDP prediction. Conclusion: Our study shows ML approaches can robustly predict elevated LVEDP and tau. ML may assist in the clinical interpretation of echocardiographic data.

Impact of left ventricular end-diastolic pressure as a marker for diastolic dysfunction on long-term outcomes in patients undergoing transcatheter aortic valve replacement

ObjectiveThe aim of this study was to investigate the proportion of elevated left ventricular end-diastolic pressure (LVEDP) as an indicator of diastolic function after transcatheter aortic valve replacement (TAVR) and its implication in predicting long-term mortality. MethodsWe analyzed retrospectively collected data on 3328 patients with severe aortic stenosis undergoing TAVR in our institution between July 2009 and June 2021. Patients were stratified into two groups based on invasive post-procedural LVEDP measurements: normal (<15 mmHg) vs. elevated (≥15 mmHg) LVEDP. ResultsMean age of the patients was 81.6 years, and 53.3% were female. Elevated post-procedural LVEDP was identified in 2408 (72.3%) patients. The 5-year mortality rates were higher in the group with elevated LVEDP compared with the group with normal LVEDP (27.4% vs. 8.3%, p = 0.01; hazard ratio [HR] 1.22, 95% CI 1.05-1.41). A multivariate model revealed the following independent predictors of mortality after TAVR: post-procedural elevated LVEDP (HR 1.24, 95% CI 1.01-1.53), pre-procedural significant tricuspid regurgitation (HR 1.24, 95% CI 1.02-1.52) and pulmonary hypertension (PH) (HR 1.53, 95% CI 1.26-1.86). In the present study, a significant paravalvular leak after TAVR was not associated with higher mortality (HR 1.45, 95% CI-0.95-2.19, p = 0.75). ConclusionElevated post-procedural LVEDP in patients who undergo TAVR is an independent predictor of all-cause mortality. Furthermore, PH and tricuspid regurgitation were also identified as predictors of mortality. These data confirm that diastolic dysfunction is an important predictor of mortality in TAVR and should be considered to guide procedure timing, favoring an early interventional approach and management in aortic stenosis patients.

Lung ultrasonography derived B-line scores as predictors of left ventricular end-diastolic pressure and pulmonary artery wedge pressure

BackgroundNon-invasive assessment of elevated left ventricular end-diastolic pressure (LVEDP) and pulmonary artery wedge pressure (PAWP) in patients with heart diseases is challenging. Lung ultrasonography (LUS) is a promising modality for predicting LVEDP and PAWP. MethodsFifty-seven stable ambulatory patients who underwent right and left heart catheterization were included. Following the procedures, LUS was performed in twenty-eight ultrasonographic zones, and the correlation between five different LUS derived B-line scores with LVEDP and PAWP was examined. ResultsThe B-line index correlated with LVEDP and PAWP, with coefficients of 0.45 (p = 0.006) and 0.30 (p = 0.03), respectively. B-line index showed an AUC of 0.76 for identifying LVEDP > 15 mmHg (p = 0.01) and an AUC of 0.73 for identifying PAWP > 15 mmHg (p = 0.008). Overall, scores performances were similar in predicting LVEDP or PAWP > 15 mmHg. A B-line index ≥ 28 was significantly associated with LVEDP > 15 mmHg (OR: 9.97) and PAWP > 15 mmHg (OR: 6.61), adjusted for age and indication for heart catheterization. ConclusionsLUS derived B-line scores are moderately correlated with PAWP and LVEDP in patients with heart diseases. A B-line index ≥ 28 can be used to predict elevated LVEDP and PAWP with high specificity.