Invasive Pressure Measurements Research Articles

Automated non-invasive quantification of myocardial work using 3D echocardiography and validation with invasive catheter measurements

Abstract Background Myocardial work is an emerging technique for the assessment of left ventricular (LV) performance. Using blood pressure as an afterload determinate offers further insight into LV mechanics than can be detected with load-sensitive parameters of ejection fraction or global longitudinal strain (GLS). Observational studies have signalled benefit in identifying vulnerable ventricles in cardiomyopathy, valvular, and coronary disease. While the reference standard for calculating myocardial work is through catheterisation, this is impractical for routine assessment. Currently, a vendor specific non-invasive index of myocardial work is commercially available, but requires subjective manual analysis and identification of valvular events. With increasing availability of 3D echocardiography (3DE) and automated analysis techniques, there is potential to derive more reproducible estimates of myocardial work. Purpose We sought to test whether global myocardial work could be accurately, non-invasively, and automatically estimated using 3DE, in combination with standard non-invasive clinical measurements. Methods Patients undergoing left heart catheterisation as part of routine care were prospectively recruited, and 3DE was performed within one hour of invasive LV pressure measurement. A validated deep learning model was used to automatically analyse the 3DE image volumes to produce GLS curves, from which a smaller number of features (principal components) were extracted. The invasive pressure traces were separated into cycles, which were each paired with the strain trace that had the minimal difference in R-R interval (and excluded if the relative R-R interval difference exceeded 25%). For each patient, an invasively-derived estimate of myocardial work was calculated as the area enclosed by the median pressure-strain (PS) loop. A multivariate regression model was used to relate a set of routine clinical parameters to the invasively-derived myocardial work, and subsequently assessed using leave-one-out cross-validation. Results A total of 131 out of 153 patients were included for analysis (2 excluded due to R-R interval mismatch, 20 excluded due to poor image or pressure trace quality), with basic demographics presented in Table I. The final parameter set consisted of 6 variables: systolic and diastolic brachial cuff pressures, peak GLS, R-R interval, and two strain curve principal components. When fit into a leave-one-out model, this resulted in a Pearson r-value of 0.86, demonstrating a very high correlation between predicted and invasively-derived myocardial work estimates, with a bias of 0 mmHg% and 95% limits of agreement (LOA) of ± 423 mmHg% (Figure 1). Conclusion This study demonstrates that fully automated and reliable estimates of myocardial work can be derived using 3DE and deep learning combined with routine clinical parameters. Automated and non-invasive approaches may facilitate increased clinical uptake of myocardial work assessment.

The effect of hydrostatic pressure on invasive coronary pressure measurements: Comparison with [15O]H2O-positron emission tomography flow data.

Fractional flow reserve (FFR) has emerged as the invasive gold standard for assessing vessel-specific ischemia. However, FFR measurements are influenced by the hydrostatic effect, which might adversely impact the assessment of ischemia. This study aimed to investigate the impact of hydrostatic pressure on FFR measurements by correcting for the height and comparing FFR with [15O]H2O positron emission tomography (PET)-derived relative flow reserve (RFR). The 206 patients were included in this analysis. Patients underwent coronary computed tomography angiography (CCTA), [15O]H2O PET, and invasive coronary angiography with routine FFR in every epicardial artery. Height differences between the aortic guiding catheter and distal pressure sensor were quantified on CCTA images. An FFR ≤ 0.80 was considered significant. The study found a reclassification in 7% of the coronary arteries. Notably, 11% of left anterior descending (LAD) arteries were reclassified from hemodynamically significant to nonsignificant. Conversely, 6% of left circumflex (Cx) arteries were reclassified from nonsignificant to significant. After correcting for the hydrostatic pressure effect, the correlation between FFR and PET-derived RFR increased significantly from r = 0.720 to r = 0.786 (p = 0.009). The average magnitude of correction was +0.05 FFR units in the LAD, -0.03 in the Cx, and -0.02 in the right coronary artery. Hydrostatic pressure has a small but clinically relevant influence on FFR measurements obtained with a pressure wire. Correcting for this hydrostatic error significantly enhances the correlation between FFR and PET-derived RFR.

Surgical removal of a knotted Swan-Ganz catheter inadvertently placed in the common carotid artery

A Swan-Ganz catheter is an intravenous device used for the invasive measurement of pulmonary capillary wedge pressure and other cardiovascular measurements often utilized in major surgical procedures and critical care units. Several device-related complications were reported in literature - arterial puncture, pneumothorax, inadvertent arterial catheter insertion due to non-ultrasound-guided placement, and formation of knots. This paper presents a case of inadvertent left carotid artery insertion of a Swan-Ganz catheter, complicated by a knot formation requiring surgical intervention to successfully remove the catheter.

Characterization of systolic and diastolic function, alongside proteomic profiling, in doxorubicin-induced cardiovascular toxicity in mice

BackgroundThe anthracycline doxorubicin (DOX) is a highly effective anticancer agent, especially in breast cancer and lymphoma. However, DOX can cause cancer therapy-related cardiovascular toxicity (CTR-CVT) in patients during treatment and in survivors. Current diagnostic criteria for CTR-CVT focus mainly on left ventricular systolic dysfunction, but a certain level of damage is required before it can be detected. As diastolic dysfunction often precedes systolic dysfunction, the current study aimed to identify functional and molecular markers of DOX-induced CTR-CVT with a focus on diastolic dysfunction.MethodsMale C57BL/6J mice were treated with saline or DOX (4 mg/kg, weekly i.p. injection) for 2 and 6 weeks (respectively cumulative dose of 8 and 24 mg/kg) (n = 8 per group at each time point). Cardiovascular function was longitudinally investigated using echocardiography and invasive left ventricular pressure measurements. Subsequently, at both timepoints, myocardial tissue was obtained for proteomics (liquid-chromatography with mass-spectrometry). A cohort of patients with CTR-CVT was used to complement the pre-clinical findings.ResultsDOX-induced a reduction in left ventricular ejection fraction from 72 ± 2% to 55 ± 1% after 2 weeks (cumulative 8 mg/kg DOX). Diastolic dysfunction was demonstrated as prolonged relaxation (increased tau) and heart failure was evident from pulmonary edema after 6 weeks (cumulative 24 mg/kg DOX). Myocardial proteomic analysis revealed an increased expression of 12 proteins at week 6, with notable upregulation of SERPINA3N in the DOX-treated animals. The human ortholog SERPINA3 has previously been suggested as a marker in CTR-CVT. Upregulation of SERPINA3N was confirmed by western blot, immunohistochemistry, and qPCR in murine hearts. Thereby, SERPINA3N was most abundant in the endothelial cells. In patients, circulating SERPINA3 was increased in plasma of CTR-CVT patients but not in cardiac biopsies.ConclusionWe showed that mice develop heart failure with impaired systolic and diastolic function as result of DOX treatment. Additionally, we could identify increased SERPINA3 levels in the mice as well as patients with DOX-induced CVT and demonstrated expression of SERPINA3 in the heart itself, suggesting that SERPINA3 could serve as a novel biomarker.

Diagnostics of acute compartment syndrome : Current gold standard and the state of science of noninvasive assessment methods

Acute compartment syndrome (ACS) is defined by a disorder of the microcirculation due to a persistent pathological pressure increase within amuscle compartment. The ischemia of the tissue leads to an initially reversible functional impairment and finally irreversible damage of the musculature, nerves and other structures. Based on the understanding of the pathophysiology, the current diagnostic concepts and treatment using the so-called dermatofasciotomy of the affected muscle compartments can be derived. In addition to the suspicion of a possible ACS based on the medical history of the patient, the findings of the clinical examination are decisive. This review article gives a summary of all the essential aspects of the diagnostics. In clinically uncertain cases and for monitoring, an objectification of the findings using instrument-based techniques is increasingly required. Nowadays, invasive needle pressure measurement is available; however, due to limited reliability, specificity and sensitivity, these measurements only represent an aid to decision guidance supporting or advising against the indications for dermatofasciotomy. The increasing demands on making a certain diagnosis and justification of a surgical intervention from a legal point of view, substantiate the numerous scientific efforts to develop noninvasive instrument-based diagnostics. These methods are based either on detection of increasing intracompartmental pressure or decreasing perfusion pressure and microcirculation. The various measurement principles are summarized in a lucid form.

Comparison of admittance and cardiac magnetic resonance generated pressure-volume loops in a porcine model

Objective. Pressure-volume loop analysis, traditionally performed by invasive pressure and volume measurements, is the optimal method for assessing ventricular function, while cardiac magnetic resonance (CMR) imaging is the gold standard for ventricular volume estimation. The aim of this study was to investigate the agreement between the assessment of end-systolic elastance (Ees) assessed with combined CMR and simultaneous pressure catheter measurements compared with admittance catheters in a porcine model. Approach. Seven healthy pigs underwent admittance-based pressure-volume loop evaluation followed by a second assessment with CMR during simultaneous pressure measurements. Main results. Admittance overestimated end-diastolic volume for both the left ventricle (LV) and the right ventricle (RV) compared with CMR. Further, there was an underestimation of RV end-systolic volume with admittance. For the RV, however, Ees was systematically higher when assessed with CMR plus simultaneous pressure measurements compared with admittance whereas there was no systematic difference in Ees but large differences between admittance and CMR-based methods for the LV. Significance. LV and RV Ees can be obtained from both admittance and CMR based techniques. There were discrepancies in volume estimates between admittance and CMR based methods, especially for the RV. RV Ees was higher when estimated by CMR with simultaneous pressure measurements compared with admittance.

The Role of Echocardiography in the Diagnosis and Prognosis of Pulmonary Hypertension.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s'), can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognosis of PH.

Inhibition of Notch3/Hey1 ameliorates peribiliary hypoxia by preventing hypertrophic hepatic arteriopathy in biliary atresia progression.

Emergingevidenceindicates the presence ofvascular abnormalities and ischemiain biliary atresia (BA), although specific mechanisms remain undefined. This study examined both human and experimental BA. Structural and hemodynamic features of hepatic arteries were investigated by Doppler ultrasound, indocyanine green angiography, microscopichistology, and invasive arterial pressure measurement. Opal multiplex immunohistochemistry, western blot, and RT-PCR were applied to assess Notch3 expression and the phenotype of hepatic arterial smooth muscle cells (HASMCs). We established animal models of Notch3 inhibition, overexpression, and knockout to evaluate the differences in overall survival, hepatic artery morphology, peribiliary hypoxia, and HASMC phenotype. Hypertrophic hepatic arteriopathy was evidenced by an increased wall-to-lumen ratio and clinically manifested as hepatic arterial hypertension, decreased hepatic artery perfusion, and formation of hepatic subcapsular vascular plexuses (HSVPs). We observed a correlation between overactivation ofNotch3 and phenotypic disruption of HASMCswith the exacerbation of peribiliary hypoxia. Notch3 signaling mediated the phenotype alteration of HASMCs, resulting in arterial wall thickening and impaired oxygen supply in the portal microenvironment. Inhibition of Notch3/Hey1 ameliorates portal hypoxia by restoring the balance of contractile/synthetic HASMCs, thereby preventing hypertrophic arteriopathy in BA.

Ultrasound-guided initial diagnosis and follow-up of pediatric idiopathic intracranial hypertension

BackgroundIdiopathic intracranial hypertension in children often presents with non-specific symptoms found in conditions such as hydrocephalus. For definite diagnosis, invasive intracranial pressure measurement is usually required. Ultrasound (US) of the optic nerve sheath diameter provides a non-invasive method to assess intracranial pressure. Transtemporal US allows imaging of the third ventricle and thus assessment for hydrocephalus.ObjectiveTo investigate whether the combination of US optic nerve sheath and third ventricle diameter can be used as a screening tool in pediatric idiopathic intracranial hypertension to indicate elevated intracranial pressure and exclude hydrocephalus as an underlying pathology. Further, to analyze whether both parameters can be used to monitor treatment outcome.Materials and methodsWe prospectively included 36 children with idiopathic intracranial hypertension and 32 controls. Using a 12-Mhz linear transducer and a 1–4-Mhz phased-array transducer, respectively, optic nerve sheath and third ventricle diameters were determined initially and during the course of treatment.ResultsIn patients, the mean optic nerve sheath diameter was significantly larger (6.45±0.65 mm, controls: 4.96±0.32 mm) and the mean third ventricle diameter (1.69±0.65 mm, controls: 2.99±1.31 mm) was significantly smaller compared to the control group, P<0.001. Optimal cut-off values were 5.55 mm for the optic nerve sheath and 1.83 mm for the third ventricle diameter.ConclusionsThe combined use of US optic nerve sheath and third ventricle diameter is an ideal non-invasive screening tool in pediatric idiopathic intracranial hypertension to indicate elevated intracranial pressure while ruling out hydrocephalus. Treatment can effectively be monitored by repeated US, which also reliably indicates relapse.

Noninvasive Assessment of Intracranial Pressure: Deformability Index as an Adjunct to Optic Nerve Sheath Diameter to Increase Diagnostic Ability

BackgroundToday, invasive intracranial pressure (ICP) measurement remains the standard, but its invasiveness limits availability. Here, we evaluate a novel ultrasound-based optic nerve sheath parameter called the deformability index (DI) and its ability to assess ICP noninvasively. Furthermore, we ask whether combining DI with optic nerve sheath diameter (ONSD), a more established parameter, results in increased diagnostic ability, as compared to using ONSD alone.MethodsWe prospectively included adult patients with traumatic brain injury with invasive ICP monitoring, which served as the reference measurement. Ultrasound images and videos of the optic nerve sheath were acquired. ONSD was measured at the bedside, whereas DI was calculated by semiautomated postprocessing of ultrasound videos. Correlations of ONSD and DI to ICP were explored, and a linear regression model combining ONSD and DI was compared to a linear regression model using ONSD alone. Ability of the noninvasive parameters to distinguish dichotomized ICP was evaluated using receiver operating characteristic curves, and a logistic regression model combining ONSD and DI was compared to a logistic regression model using ONSD alone.ResultsForty-four ultrasound examinations were performed in 26 patients. Both DI (R = − 0.28; 95% confidence interval [CI] R < − 0.03; p = 0.03) and ONSD (R = 0.45; 95% CI R > 0.23; p < 0.01) correlated with ICP. When including both parameters in a combined model, the estimated correlation coefficient increased (R = 0.51; 95% CI R > 0.30; p < 0.01), compared to using ONSD alone, but the model improvement did not reach statistical significance (p = 0.09). Both DI (area under the curve [AUC] 0.69, 95% CI 0.53–0.83) and ONSD (AUC 0.72, 95% CI 0.56–0.86) displayed ability to distinguish ICP dichotomized at ICP ≥ 15 mm Hg. When using both parameters in a combined model, AUC increased (0.80, 95% CI 0.63–0.90), and the model improvement was statistically significant (p = 0.02).ConclusionsCombining ONSD with DI holds the potential of increasing the ability of optic nerve sheath parameters in the noninvasive assessment of ICP, compared to using ONSD alone, and further study of DI is warranted.

Correlation between echocardiographic estimation of right atrial pressure and invasive measurement of central venous pressure in postoperative pediatric patients with congenital heart disease: a prospective observational study

BackgroundRight atrial pressure plays a critical role as a hemodynamic parameter in diagnosing pulmonary hypertension and other cardiac diseases, as well as guiding the treatment and prognosis of various cardiac disorders. If there is no obstruction between the inferior or superior vena cava (SVC) as central veins and the right atrium, the pressures in these veins could be considered equal to the right atrial pressure. This study aimed to examine the correlation between echocardiographic methods for estimating right atrial pressure and invasive measurements of central venous pressure (CVPi) in infants and children with congenital heart disease during the 48 h after cardiac surgery and to establish regression equations for echocardiographic estimation of central venous pressure (CVPe).ResultsWe prospectively enrolled 43 infants and children, ranging in age from 6 months to 16 years, including 20 males and 23 females. We found a significant correlation between CVPi and the ratio of the maximal diameter of IVC to the maximal diameter of the descending aorta ratio (IVCmax/DAOmax) (r = 0.529, P < 0.001), SVCS/D velocity ratio (SVCS/D) (r = 0.462, P = 0.006), right atrial vertical diameter (RAVD) (r = 0.409, P = 0.01), area (r = 0.384, P = 0.014), and tricuspid valve A wave acceleration rate (TVAAR) (r = 0.315, P = 0.048). Multiple regression analysis yielded an equation for estimating central venous pressure using four parameters related to the IVC, SVC, tricuspid valve, and right atrium. The equation is as follows: estimated CVP = 4.36 + (2.35 × IVCmax/DAOmax) + (1.06 × SVCS/D) + (0.059 × RAVD) + (0.001 × TVAAR). This equation is strongly correlated with CVPi (Pearson r = 0.698, P = 0.002).ConclusionsThe estimation of central venous pressure through a multi-parametric equation that included the ratio of the maximal diameter of the inferior vena cava to the maximal diameter of the descending aorta, the ratio of S to D velocity of the superior vena cava, the vertical diameter of the right atrium, and the acceleration rate of the A wave of the tricuspid valve demonstrated a robust correlation with invasively measured central venous pressure. To assess the accuracy of predicted pressures by this equation, further investigations are required to apply this innovative multi-parametric formula to a prospective population of pediatric patients with congenital heart disease.

Impact of ovary-intact menopause in a mouse model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) afflicts over half of all patients with heart failure and is a debilitating and fatal syndrome affecting postmenopausal women more than any other demographic. This bias toward older females calls into question the significance of menopause in the development of HFpEF, but this question has not been probed in detail. In this study, we report the first investigation into the impact of ovary-intact menopause in the context of HFpEF. To replicate the human condition as faithfully as possible, vinylcyclohexene dioxide (VCD) was used to accelerate ovarian failure (AOF) in female mice while leaving the ovaries intact. HFpEF was established with a mouse model that involves two stressors typical in humans: a high-fat diet and hypertension induced from the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME). In young female mice, AOF or HFpEF-associated stressors independently induced abnormal myocardial strain indicative of early subclinical systolic and diastolic cardiac dysfunction. HFpEF but not AOF was associated with elevations in systolic blood pressure. Increased myocyte size and reduced myocardial microvascular density were not observed in any group. Also, a broad panel of measurements that included echocardiography, invasive pressure measurements, histology, and serum hormones revealed no interaction between AOF and HFpEF. Interestingly, AOF did evoke a higher density of infiltrating cardiac immune cells in both healthy and HFpEF mice, suggestive of proinflammatory effects. In contrast to young mice, middle-aged "old" mice did not exhibit cardiac dysfunction from estrogen deprivation alone or from HFpEF-related stressors.NEW & NOTEWORTHY This is the first preclinical study to examine the impact of ovary-intact menopause [accelerated ovarian failure (AOF)] on HFpEF. Echocardiography of young female mice revealed early evidence of diastolic and systolic cardiac dysfunction apparent only on strain imaging in HFpEF only, AOF only, or the combination. Surprisingly, AOF did not exacerbate the HFpEF phenotype. Results in middle-aged "old" females also showed no interaction between HFpEF and AOF and, importantly, no cardiovascular impact from HFpEF or AOF.

Safety and Feasibility Using a Fluid-Filled Wire to Avoid Hydrostatic Errors in Physiological Intracoronary Measurements.

Using a fluid-filled wire with a pressure sensor outside the patient compared to a conventional pressure wire may avoid the systematic error introduced by the hydrostatic pressure within the coronary circulation. To assess the safety and effectiveness of the novel fluid-filled wire, Wirecath (Cavis Technologies, Uppsala, Sweden), as well as its ability to avoid the hydrostatic pressure error. The Wirecath pressure wire was used in 45 eligible patients who underwent invasive coronary angiography and had a clinical indication for invasive coronary pressure measurement at Sahlgrenska University Hospital, Gothenburg, Sweden. In 29 patients, a simultaneous measurement was performed with a conventional coronary pressure wire (PressureWire X, Abbott Medical, Plymouth, MN, USA), and in 19 patients, the vertical height difference between the tip of the guide catheter and the wire measure point was measured in a 90-degree lateral angiographic projection. No adverse events caused by the pressure wires were reported. The mean Pd/Pa and mean FFR using the fluid-filled wire and the sensor-tipped wire differed significantly; however, after correcting for the hydrostatic effect, the sensor-tipped wire pressure correlated well with the fluid-filled wire pressure (R = 0.74 vs. R = 0.89 at rest and R = 0.89 vs. R = 0.98 at hyperemia). Hydrostatic errors in physiologic measurements can be avoided by using the fluid-filled Wirecath wire, which was safe to use in the present study. This trial is registered with NCT04776577 and NCT04802681.

Bioimpedance measurement: a non-invasive diagnosis of limb compartment syndrome.

The methods for diagnosing compartment syndrome non-invasively remain under debate. Bioimpedance measurements offer a promising avenue in clinical practice, detecting subtle changes in organ impedance due to volume shifts. This study explores bioimpedance measurement as a novel, painless method for diagnosing compartment syndrome, potentially enabling continuous monitoring. This work aims to develop a prototype device for non-invasive diagnosis of compartment syndrome based on bioimpedance changes and assess initial results through in vitro experiments on inanimate biological material. We assume a change in the bioimpedance value after the application of physiological solution. Between 2018 and 2022, a prototype device for diagnosing limb compartment syndrome was collaboratively developed with the Department of Cybernetics and Biomedical Engineering at the Technical University of Ostrava, Czech Republic. This device operates by comparing bioimpedance between two compartments, one of which is pathologically affected (experiencing compartment syndrome). The Bioimpedance Analyzer for Compartment Syndrome (BACS) has been utilized to conduct measurements on inanimate biological material in laboratory settings. Two samples of duck and chicken tissue, as well as piglets, were employed for these experiments. According to the size of sample was compartment syndrome simulated by injecting 20-120mL saline into one limb (breast) while leaving the other as a control. Invasive intramuscular pressure measurements were conducted post-saline injection using a conventional device (Stryker). Changes in bioimpedance were evaluated following saline application. The non-invasive bioimpedance measurement instrument has been developed. It meets the safety requirements of European standard EN 60601-1. Measurement of accuracy showed minimal deviation for both channels (1.08% for the left channel and 1.84% for the right channel) when measuring on resistors. Ten measurements were conducted using the BACS prototype - two on chicken legs, two on duck breasts, two on duck legs, and four on piglets. Compartment syndrome simulation was achieved for all 10 measurements (IMP variance 31-45mmHg). Following saline application, a notable decrease in bioimpedance was observed in the compartment simulating compartment syndrome (decrease by 12-78Ω). Non-invasive methods could revolutionize limb compartment syndrome diagnosis, offering advantages such as non-invasiveness and continuous monitoring of compartment swelling.

Serial fractional flow reserve, coronary flow reserve and index of microcirculatory resistance after percutaneous coronary intervention in patients treated for stable angina pectoris assessed with PET.

Cardiac 15 O-water PET is a noninvasive method to evaluate epicardial and microvascular dysfunction and further quantitate absolute myocardial blood flow (MBF). The aim of this study was to assess the impact of revascularization on MBF and myocardial flow reserve (MFR) assessed with 15 O-water PET and invasive flow and pressure measurements. In 21 patients with single-vessel disease referred for percutaneous coronary intervention (PCI), serial PET perfusion imaging and fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed during PCI and after 3 months. In the affected myocardium, stress MBF and MFR increased significantly from before revascularization to 3 months after revascularization: stress MBF 2.4 ± 0.8 vs. 3.2 ± 0.8; P < 0.001 and MFR 2.5 ± 0.8 vs. 3.4 ± 1.1; P = 0.004. FFR and CFR increased significantly from baseline to after revascularization and remained stable from after revascularization to 3-month follow-up: FFR 0.64 ± 0.20 vs. 0.91 ± 0.06 vs. 0.91 ± 0.07; P < 0.001; CFR 2.4 ± 1.2 vs. 3.6 ± 1.9 vs. 3.6 ± 1.9; P < 0.001, whereas IMR did not change significantly: 30.3 ± 22.9 vs. 30.1 ± 25.3 vs. 31.9 ± 25.2; P = ns. After revascularization, an increase in stress MBF was associated with an increase in FFR ( r = 0.732; P < 0.001) and an increase in MFR ( r = 0.499; P = 0.021). IMR measured before PCI was inversely associated with improvement in stress MBF, ( r = -0.616; P = 0.004). Recovery of myocardial perfusion after PCI was associated with an increase in FFR 3 months after revascularization. Microcirculatory dysfunction was associated with less improvement in myocardial perfusion.

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.

Simple patient and lesion characteristics on coronary angiography can accurately predict FFR-proven ischemia

Abstract Aims Fractional flow reserve (FFR) measured during invasive coronary angiography (ICA), the reference standard for diagnosing coronary ischemia, potentially risks pressure wire-induced arterial wall injury. We aimed to develop a model for diagnosing coronary ischemia based on simple patient and lesion characteristics without invasive intracoronary pressure measurement. Methods We performed quantitative coronary angiography (QCA) analyses on subjects who had undergone FFR measurements during clinically indicated ICA. Clinical, ICA and QCA variables were input into a prediction model for coronary ischemia, defined as FFR ≤0.8. Least absolute shrinkage and selection operator (LASSO) regression with internal ten-fold cross-validation was implemented using R software to minimize multicollinearity and select final model variables, i.e., those corresponding to the nadir of the binomial deviation plot. Per-vessel and per-subject results were reported. Results Among 103 subjects (mean age 61 ±10 years; 74 male, 29 female) recruited from hospitals in Singapore (participants in a prospective study NCT03054324) and China, we analyzed 148 stenotic vessels visually assessed diameter (DS) ≥30%. From a dataset comprising 37 variables including baseline clinical characteristics, coronary artery morphological parameters and plaque characteristics, LASSO selected six final model variables: lesion length, minimal lumen diameter, stenosis flow reserve, DS, systolic blood pressure and diabetes, negating serious multicollinearity. The first three variables were measured on QCA, the third using ICA images acquired at rest. Our model outperformed DS ≥70% for discriminating coronary ischemia at both per-vessel (area-under-curve [AUC] 0.907 vs 0.770, p&amp;lt;0.001) and per-subject levels (AUC 0.882 vs 0.759, p&amp;lt;0.001). Per-vessel model accuracy, sensitivity, specificity, positive and negative predictive values were 85.1%, 82.4%, 93.2%, 87.1% and 83.3%, respectively; and per-subject, 83.4%, 82.0%, 85.7%, 89.3% and 76.6%, respectively. Conclusion Compared with visual diameter assessment, our LASSO-based model attained superior prediction of FFR-defined coronary ischemia using an array of variables without the need for invasive pressure measurement.

Epicardial fat is associated with adverse ventricular remodeling and diastolic dysfunction in women with ischemia but no obstructive coronary artery disease

Abstract Background Epicardial fat is a metabolically active adipose tissue depot located between the myocardium and visceral pericardium. Increased epicardial fat is associated with the development of atherosclerosis and obstructive coronary artery disease (CAD). However, information regarding relations between epicardial fat—which covers 80% of the heart surface—and cardiac function, is limited. Purpose To evaluate relations between epicardial fat and cardiac morphology and function in all four chambers of the heart. Methods To accomplish our objective, we studied 113 participants from the Women’s Ischemia Syndrome Evaluation cohort who underwent invasive measurement of left ventricular end-diastolic pressure and coronary reactivity, and comprehensive rest-stress cardiac magnetic resonance imaging (cMRI) per standardized protocols. Epicardial fat area was measured from a single high resolution steady-state free precession cine cMRI in the horizontal long axis plane (Figure 1A). Left ventricular (LV) mass, bi-ventricular volumes, and ejection fractions, were assessed using a stack of short axis cine images covering both ventricles (Figure 1B). LV concentricity was defined as the mass-to-end-diastolic volume ratio. Strain and strain rate were assessed in all four chambers by feature tracking (Figure 1C). Left atrial (LA) volume was assessed using three orthogonal long-axis cines, while right atrial (RA) area was assessed using a single horizontal long axis cine (Figure 1D). Participants were stratified by the median epicardial fat area, defined as "Low" epicardial fat (&amp;lt;13 cm2, n=48) and "High" epicardial fat (≥13 cm2, n=65). Results Participant characteristics are reported in Table 1. Notably, the majority (58%) had "High" epicardial fat and body mass index (BMI) was greater in the "High" epicardial fat group. After adjusting for BMI, however, bi-ventricular stroke index remained lower in the "High" epicardial fat group, as did bi-atrial ejection fraction (fractional area change, RA). Moreover, compared to the "Low" epicardial fat group, LV concentricity and LA booster strain were higher in the "High" epicardial fat group (Figure E-F), while LV longitudinal strain and LV early circumferential diastolic strain rate were lower (Figure G-H). No other major differences were observed between groups, including coronary reactivity or myocardial perfusion reserve. Conclusions Together, these data suggest that higher BMI is associated with increased epicardial fat that is related to adverse cardiac remodeling, along with systolic and diastolic dysfunction, across multiple cardiac chambers. Further studies would be useful to define specific mechanism contributing to these observations.Figure 1Table 1

Myocardial work index and myofilament calcium sensitivity: possible hand in hand markers of contractility in aortic valve stenosis patients - a translational study

Abstract Background In aortic valve stenosis, conventional echocardiographic parameters, such as ejection fraction (EF), are heavily influenced by the increased afterload caused by the valvular disease. Myocardial work index (GWI) quantifies myocardial deformation depending on the momentary LV pressure, potentially serving as a marker of LV contractility independent of loading conditions. Similarly, myofilament Ca2+ sensitivity (pCa50) followed the alterations of LV contractility in a rat model of pressure overload-induced heart failure. Therefore, GWI and pCa50 may also show correlation, as both can be reliable measures of contractility in diseases of chronically elevated LV afterload. Purpose Accordingly, our first aim was to assess the association of pCa50 and GWI in a rat model of pressure overload-induced heart failure and sham operated animals. We also aimed to evaluate the changes in GWI after myocardial Ca2+ sensitizing with levosimendan in aortic valve stenosis patients. Methods Firstly, on the thoracic aortic banded (n=2) and sham operated (n=3) rats speckle-tracking echocardiography and invasive LV pressure measurements were performed to calculate GWI. Using single permeabilized cardiomyocytes, pCa50 was calculated by myofilament force measurement. Secondly, to test our hypothesis in a clinical setting, 23 severe aortic valve stenosis patients (age 76±9 years, 39% female) were enrolled who received levosimendan therapy. Conventional and advanced echocardiographic measurements were performed before and after a 24-hour intravenous loading dose. We determined global longitudinal strain by speckle-tracking echocardiography, then using LV pressure curves estimated from systolic blood pressure and mean transaortic gradient, we quantified non-invasive global myocardial work index (GWI). Results In the animal study, GWI and pCa50 strongly correlated in the rats (r=0.942; p=0.017). In the clinical study, patients with a baseline EF &amp;lt;35% (n=12) had significantly increased GWI after the levosimendan therapy (533±347 vs. 660±419 mmHg%; p=0.004), while those who initially had an EF &amp;gt;35% (n=11) did not show any change (998±342 vs. 1003±275 mmHg%; p= 0.788). Also, the pre-levosimendan GWI showed a strong inverse correlation with the relative GWI change after the loading dose (r=-0.708; p=0.003). Conclusions We showed in an experimental setting, that GWI and pCa50 correlated in a rat model of pressure overload-induced heart failure and in sham operated controls. In the clinical setting, patients with severely decreased baseline EF and GWI benefited more from the Ca2+ sensitizing therapy, having better LV function after it, while those with better baseline function did not show improvement. Therefore, patients with worse baseline GWI initially might have had decreased Ca2+ sensitivity, which implies a possible correlation between GWI and pCa50 in patients with aortic valve stenosis, resembling the experimental findings.Correlation of pCa50 - GWICorrelation of GWI - relative GWI change

Abstract 16194: Relationship Between Change in Global Longitudinal Strain and Sustained Handgrip Induced Afterload as Assessed Using Invasive Left Ventricular Pressure Measurements and Machine Learning Analytics

Introduction: Global longitudinal strain (GLS) is a sensitive, quantitative measure of left ventricular (LV) systolic function and affected by afterload. We sought to compute the impact of LV systolic pressure (LVP) increase on GLS using handgrip stress during invasive LVP measurements. Methods: Patients undergoing left heart catheterization (n=51; mean age 64+/-11 years; 31% women; Table) for standard of care indications underwent echocardiography during handgrip stress with a catheter in the LV cavity. GLS and LVP were measured simultaneously over 15 seconds of continuous handgrip. GLS and LVP relationships were analyzed using linear regression and machine learning methods. Results: Sustained handgrip (HG) stress significantly increased LVP and reduced GLS. There was no significant correlation between resting and peak HG stress LVP and GLS (p= 0.32 &amp; 0.36, respectively). However, change in GLS was significantly correlated with change in LVP (p&lt;0.0001; Figure) with every 10 unit increase in LVP associated with a 0.6 reduction in GLS. The penalized maximum likelihood machine learning method was used to select key factors associated with the within subject slope of % change in GLS over % change in LVP (median slope -0.53; IQR-0.91 to -0.29). LV ejection fraction was identified as an important predictor of the GLS-LVP slope. LV ejection fraction was significantly associated with the slope (p=0.0005; Figure) with a 10 unit increase in LV ejection fraction corresponding to 0.22 increase in the slope. Conclusions: LV afterload is associated with significant decrements in GLS. LV ejection fraction is an important predictor of the GLS-LVP slope. These data provide the foundation to build models that would account for change in LVP during serial measurements of GLS thus allowing reliable comparison of repeated GLS measurements.