Measurement Of Left Ventricular Pressure 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.

Detection of contractility changes in the heart from arterial blood pressure data using symmetric Projection Attractor Reconstruction

The potential for unintended drug induced changes in cardiac contractility is a major concern in medicines development. Whilst direct left ventricular pressure (LVP) measurement is the gold standard for measuring cardiac contractility in vivo, it is resource intensive and poses a welfare burden on research animals. In contrast, arterial blood pressure (BP) measurement has fewer challenges. Symmetric Projection Attractor Reconstruction (SPAR) is a signal processing technique which transforms physiological time-series signals into a corresponding visual image (‘attractor’), amplifying morphology changes within physiological waveforms. It was hypothesized that SPAR analysis of BP signals would provide a surrogate measure of cardiac contractility by specifically amplifying the maximum slope of the systolic upstroke. BP (abdominal aorta) signals obtained from beagle dogs, treated with positive and negative inotropes, were retrospectively analysed to identify signal features that correlated with the maximum upslope of the LVP signal from simultaneously acquired LVP recordings. SPAR transformation of BP signals quantified drug induced changes in the maximum slope of the systolic upstroke. We identified key SPAR metrics that provided >0.8 correlation with the LVP maximum upslope, outperforming the BP systolic upstroke alone. This was observed for all 4 different drugs, doses and time points evaluated across studies. Thus, we conclude that the SPAR measures derived from the BP signal could be used as a first pass in vivo screen to flag any risk of drug induced changes in cardiac contractility during the conduct of non-clinical medicines development, potentially reducing or replacing the need to perform direct left ventricular measurements.

Clinical Applications of Myocardial Work in Echocardiography: A Comprehensive Review.

Left ventricular (LV) global longitudinal strain (GLS) has recently garnered attention as a reliable and objective method for evaluating LV systolic function. One of the key advantages of GLS is its ability to detect subtle abnormalities even when the ejection fraction (EF) appears to be preserved. However, it is important to note that GLS, much like LVEF, is significantly influenced by load conditions. In recent years, researchers and clinicians have been exploring noninvasive myocardial work (MW) quantification as an innovative tool for assessing myocardial function. This method integrates measurements of strain and LV pressure, providing a comprehensive evaluation of the heart's performance. Notably, MW offers an advantage over GLS and LVEF because it provides a load-independent assessment of myocardial performance. The implementation of commercial echocardiographic software that facilitates the noninvasive calculation of MW has significantly broadened the scope of its application. This advanced technology is now being utilized in multiple clinical settings, including ischemic heart disease, valvular diseases, cardiomyopathies, cardio-oncology, and hypertension. One of the fundamental aspects of MW is its correlation with myocardial oxygen consumption, which allows for the assessment of work efficiency. Understanding this relationship is crucial for diagnosing and managing various cardiac conditions. The aim of this review is to provide an overview of the noninvasive assessment of myocardial by echocardiography, from basic principles and methodology to current clinical applications.

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.

Noninvasive pressure-strain loop quantitative assessment of left ventricular function in anemic preterm infants with different modes of respiratory support

To investigate noninvasive pressure-strain loop (PSL) combined with two-dimensional speck tracking imaging and left ventricular pressure measurement in the evaluation of cardiac function changes in anemia of prematurity (AOP) with different modes of respiratory support, and to explore its value in detecting subclinical myocardial injury in preterm infants. This retrospective study included 79 preterm infants with anemia, according to different modes of respiratory support, who were divided into invasive respiratory support group (39 cases) and noninvasive respiratory support group (40 cases). A control group of 40 nonanemic preterm infants with matched age, sex, and gestational age were also included. Complete echocardiography was performed for each included infant. There are PSL parameters that used to evaluate cardiac function, including global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) among the three groups were compared. Compared with the control group, the value of GWI, GCW, and GWE were significantly lower and GWW was higher in the AOP groups (P < 0.05), and GWI, GCW and GWE were much significantly lower in the invasive respiratory support group than in the noninvasive respiratory support group (P < 0.05). There was no significant difference in GLS among the three groups (P > 0.05). Noninvasive PSL analysis can quantitatively assess myocardial work in AOP with different respiratory support, which is more sensitive than other conventional echocardiographic indices. This technique may provide a new method for monitoring subclinical myocardial injury with AOP.

Macrophage to Myofibroblast Transition Promotes Hypertension-Induced Cardiac Diastolic Dysfunction

Cardiac diastolic dysfunction is a pathological continuum of hypertension eventually leading to heart failure—which is responsible for ~13% of all deaths in the United States. A hallmark of this disease is cardiac fibrotic remodeling, in which excessive extracellular matrix components are deposited into the myocardium. Recent studies have shown the novel ability of macrophages to differentiate into a fibrotic myofibroblast-like phenotype—termed macrophage to myofibroblast transition (MMT). This phenomenon has been implicated in renal fibrosis but, has not been investigated in the heart during hypertension or diastolic dysfunction. Therefore, we hypothesize that MMT plays a causal role in cardiac fibrotic remodeling in hypertension, promoting diastolic dysfunction. As such, we seek to investigate the prevalence of myofibroblast-transitioned macrophages in the heart, as well as determine the gravity of MMT-mediated fibrotic cardiac remodeling. To understand the pathological progression of hypertension to diastolic dysfunction, we utilized the classic DOCA + NaCl model of hypertension in C57BL/6 mice. This investigation is multi-pronged, in that, we seek to gauge diastolic function in vivo, as well as investigate the microenvironment of the heart in primary in vitro experiments. To achieve this, we employ echocardiography and direct left ventricular pressure and volume measurements to determine the progression of hypertension to diastolic dysfunction in the adult mouse heart. For primary in vitro analyses, mouse hearts were isolated and digested, and leukocytes were isolated by Percoll gradient. Cells were stained with α-SMA (myofibroblast) and CD68 (monocyte/macrophage). Finally, the deposition of fibrotic collagen was assessed by both Masson’s trichrome and picrosirius red tissue stains. Mice were subjected to DOCA + salt to induce hypertension. Ten days after this treatment, the left ventricular pressure change as a function of time was measured in the left ventricle. This analysis revealed degraded heart function, realized by a significant decrease in -dp/dt as soon as ten days following the onset of hypertension. Following, another cohort of hypertensive WT mouse hearts was isolated for staining. The results of these assays revealed increased cardiac fibrosis in the hearts of hypertensive mice—likely contributing to the deficit in cardiac function. Finally, in addition to this, flow cytometric analyses of isolated cardiac leukocytes revealed that hypertensive mice had a significant increase in the α-SMA+/CD68+ population of cells in the hypertensive mouse heart, implicating MMT in the rapid pathological progression of hypertension to diastolic dysfunction. These results characterize the presence of MMT cells in the hypertensive mouse heart. Furthermore, the increase of myofibroblast transition is accompanied by decreased cardiac diastolic function and enhanced fibrotic remodeling in the heart—alluding to the role of MMT in the pathological progression of hypertension to diastolic dysfunction. Future efforts into this phenomenon involve the real-time progression of hypertension to diastolic dysfunction via echocardiography, as well as a final, definitive measurement of diastolic function by PV loop. Finally, we will employ an angiotensin II model of hypertension to ensure that this phenomenon is encapsulated in other forms of hypertension, rather than just the DOCA + Salt model. We thank our sources of funding:NIG R01-HL146713, AHA 23TPA1076467. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

L-theanine abates oxidative stress and mitochondrial dysfunction in myocardial ischemia-reperfusion injury by positively regulating the antioxidant response

L-theanine (L-THE), a non-protein amino acid isolated from Camelia sinensis, has antioxidant properties that could prevent oxidative damage and mitochondrial dysfunction generated by myocardial ischemia and reperfusion (I/R) injury. The present study aimed to identify the effects of pretreatment with L-THE in rat hearts undergoing I/R. Wistar rats received vehicle or 250 mg/Kg L-THE intragastrically for 10 days. On day 11, hearts were removed under anesthesia and exposed to I/R injury in the Langendorff system. Measurement of left ventricular developed pressure and heart rate ex vivo demonstrates that L-THE prevents I/R-induced loss of cardiac function. Consequently, the infarct size of hearts subjected to I/R was significantly decreased when L-THE was administered. L-THE also mitigated I/R-induced oxidative injury in cardiac tissue by decreasing reactive oxygen species and malondialdehyde levels, while increasing the activity of antioxidant enzymes, SOD and CAT. Additionally, L-THE prevents oxidative phosphorylation breakdown and loss of inner mitochondrial membrane potential caused by I/R, restoring oxygen consumption levels, increasing respiratory control and phosphorylation efficiency, as well as buffering calcium overload. Finally, L-THE modifies the expression of genes involved in the antioxidant response through the overexpression of SOD1, SOD2 and CAT; as well as the transcriptional factors PPARα and Nrf2 in hearts undergoing I/R. In conclusion, L-THE confers cardioprotection against I/R injury by preventing oxidative stress, protecting mitochondrial function, and promoting overexpression of antioxidant genes. More studies are needed to place L-THE at the forefront of cardiovascular research and recommend its therapeutic use.

Hemodynamic performance of self-expandable transcatheter aortic valve replacement systems during valve deployment.

Little is known about valve hemodynamic performance during the Evolut and Neo deployment course. We aimed to evaluate transvalvular mean and peak-to-peak gradients over several intraprocedural timepoints during TAVR with Evolut PRO+ (Medtronic) and Neo (Boston Scientific) systems. This was single-center pilot sub-study from the SavvyWire EFficacy and SafEty in Transcatheter Aortic Valve Implantation Procedures (SAFE-TAVI) trial. Participants received either the Evolut PRO+ or Neo for native valve severe aortic stenosis and the SavvyWire (OpSens Medical) was used for device delivery, pacing, and continuous left ventricular and aortic pressure measurements. For the Evolut, evaluation was done for baseline, two-thirds of valve deployment (still recapturable), 90% of valve deployment (no longer recapturable), and post-deployment hemodynamics. For the Neo, analysis was done at baseline, after the first step (top-crown deployment), and at final status. Nineteen patients were included (Evolut = 15; Neo = 4). There were no statistically significant changes in peak-to-peak gradients (44 mm Hg [IQR:33-69] vs 43 mm Hg [IQR:26-62], P = .41) between baseline and two-thirds of valve deployment in the Evolut patients. There was a significant decrease in mean (40 mm Hg [IQR:32-54] vs 14 mm Hg [IQR:10-18], P less than .001) and peak-to-peak (43 mmHg [IQRS:26-62] vs 9 mm Hg [IQR:8-13], P less than .001) transvalvular gradients between two-thirds and 90% of valve deployment for Evolut. Neo patients exhibited a decrease in transvalvular gradients after top-crown deployment (42.5 mm Hg baseline vs 13 mm Hg). Transvalvular gradients did not vary between the point of "no-recapture" compared to baseline values in patients receiving the Evolut, whereas a significant reduction in transvalvular gradients was observed when the valve was deployed at 90% and fully deployed. The Neo valve was slightly obstructive after the first step of deployment.

Mitral Annulus Calcium Score in Patients With Calcific Mitral Stenosis Undergoing Invasive Hemodynamic Assessment.

Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown. This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm2. Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation (P=0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area (r=0.07; P=0.6) or mitral valve gradient (r=-0.03; P=0.8). MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC-related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.

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

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 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.

P2: Impella Smart Assist Technology and Hemodynamics Management in Cardiogenic Shock Management

Background: Smart Assist Impella pumps provide enhanced hemodynamic metrics via real-time assessment of aortic pressure (AoP), left ventricular pressure (LVP), cardiac output (CO) and cardiac power output (CPO). These data can constitute powerful management tools for clinicians yet information on the Smart Assist Technology algorithms and calculations remains scarce. This case reports illustrates the importance of an in-depth understanding of this newer technology to effectively manage cardiogenic shock patients on Impella support. Method: A 64yo man with cardiogenic shock supported with Impella 5.5 as a bridge to transplant had been on support for 27 days, with stable hemodynamics on P8, flowing 4.5 LPM. On day 28 patient experienced suction alarms and LVDP <-40mmHg prompting the team to reduce P level, administer fluid and attempt Impella repositioning. None of the interventions resolved the issue and consideration was given to reducing support to P2 and weaning or exchanging the Impella. The pump appeared correctly positioned by echo and hemolysis markers were negative. Careful review of patients’ data demonstrated a discrepancy between the transduced radial artery MAP at 73 mmHg and the aortic pressure measured by the Impella fiber optic sensor at 42 mmHg. This prompted a review of the LVP metric. The Impella Left ventricular pressure is calculated in real time by subtracting from the AoP the differential pressure gradient between pump outlet and inlet as derived from the motor current. An erroneous Ao signal input will result in an inaccurate LVP. Furthermore, the Impella suction alarm algorithm utilizes a sustained low LVDP as a trigger and can thus be triggered erroneously if the Ao signal is inaccurate. The suctions alarms and the low LVP were determined to be caused by drifting data feed from the Impella aortic fiber optic sensor. An Impella Ao signal bedside recalibration based on transduced MAP resolved the suction alarms. Result A drifting AoP signal resulted in an erroneous LVP measurements and subsequent suction alarms. Fiber optic technology does not require periodic calibrations once in vivo. Per IFU, the accuracy of the Ao is 1.9mmHg and the accuracy of the LV is 8.8 mmHg. In this case, the recalibration of the AO signal resolved the suction alarms and low LVP. Decision was made to not undertake an invasive pump exchange and continue supporting the patient on the implanted pump managing the metrics with daily manual recalibration. The patient was supported for an additional 17 days demonstrating optimal perfusion pressure and LV unloading and successfully underwent orthotopic heart transplant on Impella day 45. Conclusion: Impella Smart Assist technology is a powerful tool to manage patients’ hemodynamics. An in-depth understanding of the technology and its algorithms is crucial in delivering optimal patient care and preventing erroneous data feed from guiding hemodynamic management.Figure 1. Impella Smart Assist metrics. A. Stable on P8. B. Suction alarm generated by low LVDP. C. Persistent alarms despite fluid bolus and lower P level. D. Suction alarm resolved by Ao recalibrationFigure 2. LVP Calculation

Coronary artery disease is associated with impaired atrial function regardless of left ventricular filling pressure

BackgroundLeft atrial (LA) strain is impaired in left ventricular (LV) diastolic dysfunction, associated with increased LV end diastolic pressure (LVEDP). In patients with preserved LV ejection fraction (LVEF), coronary artery disease (CAD) is known to impair LV diastolic function. The relationship of LVEDP with CAD and impact on LA strain is not well studied. Methods and resultsPatients with LVEF >50% (n = 37, age 61 ± 7 years) underwent coronary angiography, high-fidelity LV pressure measurements and cardiac magnetic resonance imaging. LA volumes, LA emptying fraction (LAEF), LA reservoir strain (LARS) and LA long-axis shortening (LALAS) were measured. By coronary angiography, patients were assigned into 3 groups: severe-CAD (n = 19, with obstruction of major coronary arteries >70% and/or history of coronary revascularization), mild-to-moderate-CAD (n = 10, obstruction of major coronary arteries 30–60%), and no-CAD (n = 8, obstruction of major coronary arteries and branches <30%). Overall, LVEF was 65 ± 8% and LVEDP was 14.4 ± 5.6 mmHg. Clinical characteristics, LVEDP and LV function measurements were similar in 3 groups. Severe-CAD group had lower LAEF, LALAS and LARS than those in no-CAD group (P < 0.05 all). In regression analysis, LARS and LALAS were associated with CAD severity and treatment with Nitrates, whereas LAEF and LAEFactive were associated with CAD severity, treatment with Nitrates and LA minimum volume (P < 0.05 all). LAEFpassive was associated with LVED volume (P < 0.05). ConclusionsLA functional impairment may be affected by coexistent CAD severity, medications, in particular, Nitrates, and loading conditions, which should be considered when assessing LA function and LA-LV interaction. Our findings inspire exploration in a larger cohort.

Masked Hypertension in Pediatric Heart Transplant Recipients.

Masked hypertension (HTN), especially, isolated nocturnal HTN (INH) has been shown to be a risk factor for cardiovascular disease (CVD) but is not studied well in pediatric heart transplant (PHT) patients. Ambulatoryblood pressuremonitoring (ABPM) is known to identify patients with HTN but is not used routinely in PHT. A single-center, prospective, cross-sectional study of PHT recipients was performed to observe the incidence of masked HTN using 24-h ABPM. The relationship between ABPM parameters and clinical variables was assessed using Spearman correlation coefficient. p value < 0.05 was considered significant. ABPM was performed in 34 patients, mean age 14 ± 5years, median 5.5years post-PHT. All patients had normal cardiac function, left ventricular mass index and blood pressure measurements in the clinic. Four patients had known prior HTN and on medications, one of them was uncontrolled. Of the remaining 30 patients, 18 new patients were diagnosed with masked HTN, of which 14 had INH. Diurnal variation was abnormal in 82% (28/34) patients. 24-h diastolic blood pressure (DBP) index correlated with glomerular filtration rate (GFR) (r = -0.44, p = 0.01). There was no correlation between other ABPM parameters with tacrolimus trough levels. ABPM identified masked HTN in 60% of patients, with majority being INH. Abnormal circadian BP patterns were present in 82% and an association was found between GFR and DBP parameters. HTN, especially INH, is under-recognized in PHT recipients and ABPM has a role in their long-term care.

Correlation between Echocardiographic Diastolic Parameters and Invasive Measurements of Left Ventricular Filling Pressure in Patients with Takotsubo Cardiomyopathy

The extent of diastolic dysfunction is of clinical importance in the risk stratification and management of patients with Takotsubo cardiomyopathy (TC). Standard echocardiographic indices of diastolic dysfunction have robust predictive ability in assorted disease states, but have not been validated in TC. The aim of this study was to compare Doppler metrics of diastolic function against catheterization-measured filling pressures in TC. Patients with TC who met inclusion and exclusion criteria were evaluated using echocardiography and catheterization performed within 24hours. Both left ventricular (LV) end-diastolic pressure and LV pre-A diastolic pressure were obtained from catheterization tracings. The echocardiographic parameters for diastolic function were extracted using the American Society of Echocardiography recommendations and a previously validated regression equation for mean left atrial pressure (mLAP). A total of 51 patients with TC were included. Patients were predominantly women (72.5%), with a mean age of 58±13years and a mean ejection fraction of 24±10 %. E/e' ratio (septal, average, and lateral) and calculated mLAP correlated positively with catheterization LV pre-A, with fair to moderate correlation (coefficient range, 0.38-0.44). The t-test mean difference between LV pre-A pressure and calculated mLAP was 0.77±7.34mm Hg (95% CI, ±14.68mm Hg) suggesting inconsistent measures. mLAP also exhibited poor diagnostic ability to discriminate elevated LV pre-A diastolic pressure, with an area under the receiver operating characteristic curve of 0.69 (95% CI, 0.50-0.88). Commonly used echocardiographic parameters for diastolic function demonstrated less-than-optimal correlation, with poor sensitivity and specificity, compared with invasively measured LV end-diastolic pressure or LV pre-A wave diastolic pressure in patients with TC. Precise characterization of LV filling pressure in patients with TC using contemporary noninvasive echocardiographic parameters appears challenging. Invasive measurements of filling pressure should remain the gold standard for optimal risk stratification and management of patients with TC.

Validation of non-invasive assessment of myocardial work in aortic stenosis: improvements by modifying the method for estimating the left ventricular pressure waveform

Abstract Introduction Non-invasive myocardial work (MW) index incorporates strain by speckle-tracking echocardiography (STE) and individually estimated left ventricular pressure (LVP) curves to calculate the area of the pressure strain loop without the need for invasive LVP measurements. The method was validated in patients without aortic stenosis (AS) where a reference pressure curve is adjusted for individually measured aortic and mitral valve events and the peak LVP is defined by the brachial artery cuff pressure. Before applying this method in patients with AS, potential limitations which can influence the area of the pressure strain loop, such as the LVP curve profile, correct scaling of peak LVP and correct assessment of aortic events must be addressed. Purpose The present study aimed to assess the impact of the potential limitations specific to patients with AS and thereby the validity of non-invasive MW index in patients with AS. Methods In 20 patients with severe AS we obtained simultaneous LVP, by a micromanometer-tipped catheter, and strain by STE. For each patient, LVP curve estimations were done using three different models: 1. The established LVP reference model based on patients without AS. 2. Enhancement of the established LVP reference model by defining aortic valve opening with diastolic cuff pressure. 3. A new AS specific LVP reference model based on our current invasive measurements. Valvular events were determined by 2D and Doppler echocardiography, and peak LVP estimated as a sum of mean trans-aortic gradient and systolic cuff pressure. Estimated LVP curve tracings were thereafter directly compared with simultaneous invasive measurements (Figure 1). Furthermore, area of the pressure-strain loops using the different estimations of LVP curve were calculated to assess MW and compared to simultaneous invasive measurements for direct comparison. Results All three methods had excellent average correlation coefficient between estimated and invasively measured LVP traces. However, estimations with the AS specific reference curve and those enhanced with incorporation of diastolic pressure for aortic valve opening had a higher correlation coefficient (r=0.99, p&amp;lt;0.001) and a more physiological profile during early systole compared to that of the previously validated reference curve (r=0.96, p&amp;lt;0.001) (Figure 1). Furthermore, there was an excellent correlation (r=0.98, p&amp;lt;0.001) and good agreement between MW calculated with all three non-invasive estimation methods and invasive LVP (Figure 2). Conclusions The present study is the first to confirm the validity of non-invasive MW in patients with AS. Furthermore, a AS specific reference curve and the enhanced reference curve incorporating diastolic cuff pressure to define aortic valve opening both increased the accuracy of the estimated LVP curve and hence estimation of MW. This could be pivotal when assessing AS patients with marked regional differences such as LBBB or regional ischaemia. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Oslo University Hospital Rikshospitalet

The relationship of left ventricular outflow tract presystolic wave and 24-h ambulatory blood pressure measurements.

Left ventricular outflow tract (LVOT) presystolic wave is a novel marker for several cardiac conditions. It is shown to be related to several cardiac conditions. The aim of this study is to investigate the relationship between LVOT presystolic wave and 24-h ambulatory blood pressure measurements. A total of 194 patients who came to the cardiology outpatient clinic were prospectively enrolled in the study. After demographic and clinical inquiry, blood biochemistry and hemogram tests were performed. Each patient was evaluated with echocardiography and 24-h ambulatory blood pressure measurement. The patients were divided into hypertensive and nonhypertensive groups regarding their ambulatory blood pressure measurements and the LVOT presystolic wave of the groups on echocardiography was compared. The hypertensive group was significantly older (59.34 ± 11.15 vs. 49.89 ± 15.43; P < 0.001). Presystolic wave presence (96.2 vs. 29.5%; P < 0.001) and velocity (62.23 vs. 29.42; P < 0.001) were higher in patients with hypertension. Blood pressure values and LVOT amplitudes showed a positive correlation ( P < 0.001; r = 0.326). In multivariable logistic regression analysis; age, BMI and the presystolic wave were independently associated with hypertension (odds ratio: 8.09; P < 0.001). LVOT presystolic wave is associated with systemic hypertension and it could be used as a predictor for systemic hypertensive patients.

Prolonged Asynchronous Left Ventricular Isovolumic Relaxation Constant in Ascending Compared to Descending Thoracic Aortic Stenosis for Chronic Early Left Ventricular Afterload and Late Left Ventricular Afterload Increase.

Background: In arterial hypertension, left ventricular relaxation is affected early on in relation to a chronic difference in peak left ventricular afterload with early development of HF. Objective: in ascending compares to descending thoracic aortic stenosis, resulting in chronic late and early LV afterload increase, to assess the left ventricular isovolumic relaxation pressure decay constant through regression analysis, a parameter of left ventricular relaxation on the 4th and 8th week period from invasive left ventricular pressure measurements. Methods: fourteen pigs underwent posterolateral thoracotomy for ascending aortic stenosis, resulting in chronic early left ventricular afterload increase (EL = 6], or descending thoracic aortic stenosis creating chronic late systolic left ventricular load (LL = 8]. Exponential regression with nonzero asymptote for τ assessment, with linear and nonlinear regression were performed on isovolumic relaxation pressure decay from the left ventricular invasive pressure measurements on 4th and 8th week. Two-way repeated measurement ANOVA, post-hoc Tukey test and linear regression were performed for statistical analysis. Results presented are mean ± SEM or median (quartiles], with significance is at p < 0.05. Results: The ascending aortic stenosis associated with prolonged biexponential asynchronous τ, compared to the descending thoracic aorta stenosis, resulted in data that were different at the 8th week in presence of respirations (interaction p < 0.05]. Monoexponential and linear τ were not different in either respiration being preserved or suspended transitionally and in preload reduction. Preload sensitive response of τ was found in ascending compared to descending thoracic aortic banding that reduced in EL and in LL it increased with load reduction (p < 0.05]. These results indicated that τ is not different in and between LV afterloading conditions in a chronic setting, although it indicates that myocardial ischemia is present and that it is greater in ascending aortic banding, compared to descending thoracic aorta banding at the 8th week. Conclusion: In different sequence of the left ventricular afterload, ventricular relaxation is affected early on, having in EL compared to LL prolonged biexponential asynchronous left ventricular relaxation constant, thus indicating the development left ventricular myocardial ischemia and different elastic recoil in an invasive left ventricular hemodynamic assessment.

Manipulation of Left Ventricular Loading Conditions is Necessary to Identify Diastolic Dysfunction in Swine with Repetitive Pressure Overload‐Induced HFpEF

ObjectiveDiagnosis of heart failure with preserved ejection fraction (HFpEF) is often complicated by the fact that many patients exhibit normal left ventricular (LV) mechanics at rest with a reduction in diastolic compliance that is only revealed when loading conditions are altered (e.g., during exercise stress). In an effort to identify parameters of diastolic function that could be utilized to detect alterations in compliance without manipulation of LV loading conditions, we utilized invasive hemodynamic analysis and speckle‐tracking echocardiography (STE) to assess diastolic strain and stiffness in swine with repetitive pressure overload (RPO)‐induced HFpEF.MethodsSwine (n=13) were subjected to 2‐weeks of RPO via daily intravenous administration of phenylephrine (PE; 400 ug/min; 1 hour/day) through an indwelling jugular vein catheter. Indices of LV relaxation as well as LV minimum and end‐diastolic pressure were obtained invasively before and after RPO at rest and during transient PE‐induced alterations in loading conditions. STE (Vivid 9; GE) was also performed throughout a single cardiac cycle to collect circumferential diastolic strain data, which were used alongside echocardiography‐derived measurements of chamber radius and wall thickness as well as catheter‐derived measurements of LV pressure to calculate regional and global circumferential subendocardial diastolic stiffness before and after RPO.ResultsCompared with baseline measurements, 2‐weeks of RPO did not significantly increase the time constant of LV relaxation (Tau; Figure A) or decrease the rate of LV pressure change during isovolumic relaxation (dP/dtmin; Figure B). Circumferential subendocardial stiffness derived via STE across a single cardiac cycle at rest was also unaffected by RPO (Figure C), despite a significant reduction in diastolic compliance that was revealed by construction of two‐point end‐diastolic pressure‐volume curves (Figure D) after manipulation of loading conditions (Figure E). Interestingly, single‐cycle STE‐derived stiffness measurements made during acute pressure overload were also similar at baseline and after RPO due to persistent elevations in LV minimum diastolic pressure during PE infusion at both timepoints.ConclusionsAlthough reductions in LV diastolic compliance are evident after chronic RPO when loading conditions are manipulated, abnormalities in LV mechanics are not exhibited at rest even when STE is used to assess diastolic stiffness throughout a single cardiac cycle. These findings highlight the challenges associated with identification of myocardial stiffening at rest in patients with HFpEF and reinforce the importance of studying LV mechanics under variable loading conditions.