Micromanometer-tipped Catheter Research Articles

A novel imaging-based method to estimate left ventricular filling pressure

Abstract Background There is a clinical need in heart failure diagnostics to have a non-invasive measure of left ventricular (LV) filling pressure. Echocardiographic parameters may be used to differentiate between normal and elevated left ventricular (LV) filling pressure, but do not provide a quantitative estimate of the filling pressure. Purpose To establish a non-invasive method for estimating LV filling pressure and construction of the LV diastolic pressure curve. Methods Retrospective study in 100 patients with suspected coronary artery disease. Ground truth filling pressure (i.e. LV pre-atrial contraction pressure, which is shown to approximate mean left atrial pressure) was measured by LV micromanometer-tipped catheters. Non-invasive filling pressure was estimated as the sum of minimum LV pressure (minPLV) and the maximum early-diastolic atrio-ventricular pressure difference (∆PA-V), as shown in Figure 1. MinPLV was estimated by a regression model trained in 81 patients, which included an estimate of the time constant of τ (Figure 1) and echocardiographic and demographic parameters. ∆PA-V was computed by a simplified Navier-Stokes momentum conservation equation. Accuracy of filling pressure estimate was evaluated in a test cohort of 19 patients. Results The strongest predictor of minPLV was τ (R=0.71) followed by LA reservoir strain (R=0.65), LV systolic pressure (R=0.23) and body mass index (R=0.37), all of them independent predictors. There was good agreement between estimated and measured τ (Bias -0.0069s and limits of agreement <0.0195s). When combining estimated τ and the three other predictors in a regression model, there was good agreement between estimated and measured minPLV: Bias -0.5 mmHg, limits of agreement <1.9 mmHg (±2SD). Estimated LV filling pressure also showed good agreement with measured values: Bias 0.0 mmHg, limits of agreement <3.1 mmHg, shown in Figure 2. The diastolic pressure curve was estimated with good accuracy (diastolic meanPLV had bias and limits of agreement were respectively 0.2 and <3.2mmHg). Conclusions The proposed non-invasive method estimated LV filling pressure with good accuracy in a population with coronary artery disease. The method also allowed approximation of the LV diastolic pressure curve. The method needs validation in larger populations and in other phenotypes. Method to calculate LV filling pressure LV filling pressure (pre-A) agreement

Abstract 4117657: Targeting GPR39 for Hypoxia-induced Pulmonary Hypertension in Mice

Background: Primary pulmonary arterial hypertension (PAH) is a disease affecting young subjects. It has very poor prognosis and optimal treatment is not available. 15-hydroxyeicosatetraenoic acid (15-HETE), a potent vasoconstrictor, has been implicated in the pathogenesis of PAH. Elevated levels of 15-HETE have been shown to be associated with worse prognosis in patients with PAH. Oral ingestion of 15-HETE leads to development of PAH in rodents. We recently showed that 15-HETE is the endogenous agonist for the G-protein coupled receptor 39 (GPR39) present in vascular smooth muscle cells. Hypothesis: We, therefore, hypothesized that global deletion of GPR39 (knock-out [KO] mice) would protect from PAH by removing the receptor through which 15-HETE causes vasoconstriction. Methods: Accordingly, 13 wild-type (WT) and 16 KO mice were placed in a hypoxia chamber (10% O 2 ). Litter-mate controls (7 WT and 13 KO) were subjected to normoxia (room air, 21% O 2 ). At the end of 4 weeks heart rate as well as aortic and right ventricular (RV) pressures were measured (latter using micromanometer-tipped catheter), and the animals were then euthanized for measurement of RV wall thickness and RV size from which RV wall stress was calculated. Results: Heart rate and systolic blood pressure were not different between the 4 groups . WT hypoxic animals developed PAH with peak RV systolic pressures (RVSP) being significantly higher than normoxic WT and hypoxic WT and hypoxic KO mice. (Figure 1) Similar results were noted for RV end-diastolic pressure (Figure 2) and RV wall stress (Figure 3). Conclusions: By deleting GPR39, the target for 15-HETE, we were able to prevent hypoxia induced PAH and RV dysfunction. Pharmacological inhibition of GPR39 may open new frontiers in the treatment of PAH.

Novel clinical method: left ventricular diastolic pressure curve by echocardiography

Abstract Background A non-invasive clinical method for construction of the systolic part of the left ventricular (LV) pressure curve was recently introduced. There is, however, no clinical method available to construct the LV diastolic pressure curve. Purpose The aim of this study was construction of patient-specific LV diastolic pressure curves from echocardiographic data and have initial validation against simultaneously acquired pressure curves by high-fidelity LV pressure catheters (micromanometers). Methods The study included 108 patients referred for diagnostic left heart catheterization due to suspected coronary artery disease. 81 patients were used as a training cohort. The construction of a diastolic pressure curve is based on a reference unitless pressure trace and seven key pressure-time diastolic events estimated in each patient. The reference diastolic pressure trace was generated from a group of 8 patients with LV pressures recorded by micromanometer. Each individual pressure trace from the reference cohort was first annotated with the occurrence of the key diastolic events: mitral valve (MV) opening, minimum LV pressure, peak of early-diastolic mitral flow velocity (E) and start and peak of atrial contraction-induced velocity (A), and MV closure. Then the temporal intervals between these events were normalized before calculating an averaged pressure curve (Figure 1, panels A-C). A patient-specific LV diastolic pressure curve was constructed by adjusting the standard curve according to estimated LV pressure at the key diastolic events (shown in Figure 1D). The estimation of the pressure-time instants is based on the LV volume temporal transient, used to estimate filling flow rate (Q=dV/dt) and flow acceleration and deceleration (dQ/dt=d2V/dt2), as well as a set of biomarkers including left atrial reservoir strain, peak systolic LV pressure, and body mass index. LV volume temporal traces were generated by combining global 2D volumes with global longitudinal strain. The ability to generate patient-specific diastolic LV pressure curves was validated in a second cohort of 7 patients studied with micromanometer-tipped catheters. Echocardiography and LV pressure were recorded from the same series of beats and recordings were done during breath-hold at end-expiration. The agreement was accessed qualitatively and considering the mean diastolic LV pressure. Results There was good agreement between measured and estimated LV diastolic pressure curves, qualitatively and quantitatively, via mean diastolic PLV: Bias 0.2 mmHg, limits of agreement <3.2 mmHg (Figure 1D-F). Conclusions The results suggest that the LV diastolic pressure curve can be estimated by echocardiography. The method needs validation in larger populations.Non-invasive diastolic LV pressure curve

Acute Hemodynamic Effect of a NovelDual-Vein, Multisite Biventricular Pacing Configuration.

Biventricular pacing (BVP) from multiple left ventricular (LV) sites could enhance the efficacy of cardiac resynchronization therapy (CRT) by engaging a greater myocardial mass. The goal of this study was to evaluate the acute hemodynamic effect of various multisite pacing (MSP) configurations against conventional BVP. Twenty patients with nonischemic dilated cardiomyopathy and left bundle branch block (mean age: 59 ± 14 years; LV ejection fraction: 27% ± 6%; native QRS: 171 ± 16 milliseconds) were investigated during a routine CRT implant procedure. In addition to conventional right atrial and right ventricular leads, 2 quadripolar leads were placed in the distant coronary venous branches. LV hemodynamics was evaluated by using a micromanometer-tipped catheter during atrioventricular BVP with 4 LV lead configurations: single-lead conventional BVP; single-lead multipoint pacing; triventricular pacing from distal dipoles of 2 LV leads; and maximum MSP (MSP-Max) from 4 dipoles of 2 LV leads. Compared with right atrial pacing, any BVP configuration produced a significant increase in the maximal LV diastolic pressure rise (LVdP/dTMax) (amedian relative increase of 28% [IQR: 8%-45%], 25% [IQR: 18%-46%], 36% [IQR: 18%-54%], and 38% [IQR: 28%-58%], respectively; all, P< 0.001). MSP-Max but no other multisite BVP generated a significant increase of the maximal LVdP/dTMax than conventional BVP (P=0.041). Increased LVdP/dTMax during MSP-Max was associated with greater LV diameter and lower LV ejection fraction, independently of the QRS width. The study shows the hemodynamic advantage of a novel dual-vein MSP-Max configuration that could be useful for CRT in patients with advanced LV remodeling.

Non-invasive myocardial work in aortic stenosis: validation and improvement in left ventricular pressure estimation.

The non-invasive myocardial work index (MWI) has been validated in patients without aortic stenosis (AS). A thorough assessment of methodological limitations is warranted before this index can be applied to patients with AS. We simultaneously measured left ventricular pressure (LVP) by using a micromanometer-tipped catheter and obtained echocardiograms in 20 patients with severe AS. We estimated LVP curves and calculated pressure-strain loops using three different models: (i) the model validated in patients without AS; (ii) the same model, but with pressure at the aortic valve opening (AVO) adjusted to diastolic cuff pressure; and (iii) a new model based on the invasive measurements from patients with AS. Valvular events were determined by echocardiography. Peak LVP was estimated as the sum of the mean aortic transvalvular gradient and systolic cuff pressure. In same-beat comparisons between invasive and estimated LVP curves, Model 1 significantly overestimated early systolic pressure by 61 ± 5 mmHg at AVO compared with Models 2 and 3. However, the average correlation coefficients between estimated and invasive LVP traces were excellent for all models, and the overestimation had limited influence on MWI, with excellent correlation (r = 0.98, P < 0.001) and good agreement between the MWI calculated with estimated (all models) and invasive LVP. This study confirms the validity of the non-invasive MWI in patients with AS. The accuracy of estimated LVP curves improved when matching AVO to the diastolic pressure in the original model, mirroring that of the AS-specific model. This may sequentially enhance the accuracy of regional MWI assessment.

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

Novel multi-site, multi-point biventricular pacing configuration: acute haemodynamic benefit

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by the research grant of the AZV (Ministry of Health of the Czech Republic) Background Biventricular pacing (BVP) using multiple left ventricular (LV) sites may augment the hemodynamic effect of cardiac resynchronisation therapy (CRT) by engaging a greater mass of the myocardium. Purpose To evaluate the acute hemodynamic effect of a novel multi-site, multi-point BVP configuration. Methods The study investigated 18 patients with idiopathic dilated cardiomyopathy and left bundle-branch block during implantation of a BVP device (age: 59 ± 14 years, female gender: 7 [39%], LVEF: 27 ± 6%, native QRS: 171 ± 16 ms). Conventional leads were placed in the right atrium (RA) and ventricle (RV), one quadripolar LV lead (Quartet, Abbott, Abbott Park, IL, USA) was positioned in the posterolateral and another one in lateral or anterolateral coronary vein. Individual bipoles of all leads were connected through a splitter to separate external cardiac stimulators. Hemodynamics was evaluated using a micromanometer-tipped catheter (Micro-Cath, Millar, Tx, USA) located in the LV during RA pacing above sinus rate and five atrio-ventricular sequential pacing configurations at the same rate: 1.) RA+RV, 2.) RA + RV + distal bipole of the LV lead with greater dP/dT („conventional BVP"), 3.) RA + RV + distal and proximal bipoles of the LV lead with greater dP/dT („single-lead multi-point BVP"), 4.) RA + RV + distal bipoles of both LV leads („two-lead multi-site BVP"), and 5.) sequentional pacing RA + RV + all bipoles of both LV leads interconnected to a mesh („maximum BVP"). Results Compared to RA pacing, LV dP/dT was significantly greater during all BVP pacing configurations (RA pacing: 1940 ± 507 mmHg/s vs. conventional BVP: 2431 ± 855 mmHg/s, single-lead multi-point BVP: 2539 ± 740 mmHg/s, two-lead multisite BVP: 2517 ± 836 mmHg/s, and "maximum BVP": 2685 ± 893 mmHg/s, all p&amp;lt;0.001, Figure 1), but not during RA-RV pacing (2014 ± 721 mmHg/s, p=0.12). In addition, dP/dT was significantly greater during "maximum BVP" compared to conventional BVP (p=0.05). Conclusion Compared to RA pacing and conventional BVP, the greatest increase in LV contractility was achieved with a novel multi-site, multi-point "maximum BVP" configuration. These preliminary findings provide a rationale for designing new approaches to CRT.

Efficacy of His Bundle Pacing on LVRelaxation and Clinical Improvement in HFandLBBB.

This study aimed to compare acute hemodynamic improvements and responses to His bundle pacing (HBP) and conventional biventricular pacing (BVP). HBP can correct left bundle branch block (LBBB) and may be an alternative cardiac resynchronization therapy (CRT) to BVP. Fourteen consecutive patients with heart failure (HF) and typical LBBB who required CRT were enrolled. The acute hemodynamic responses during HBP and BVP were compared using a micromanometer-tipped catheter inserted into the left ventricle (LV) before CRT. Each configuration was compared with AAI mode. A permanent HBP device was implanted when LBBB correction threshold was≤1.5V at 1.0ms, and remaining patients were treated with BVP. Clinical and echocardiographic improvements were assessed during a 12-month follow-up period. The LV contractile index (positive maximal rate of LV pressure rise [dP/dtmax]) increased similarly during HBP and BVP (18.8% ± 6.4% vs 18.0% ± 10.2%; P = 0.810). LV relaxation indices (negative dP/dtmax and tau) were significantly improved during HBP compared with BVP (negative dP/dtmax: 14.3% ± 5.5% vs 3.1% ± 8.1%; P< 0.001; tau: 7.2% ± 4.3% vs -0.8% ± 8.1%; P = 0.001). Nine (64%) patients received permanent HBP devices, while 5 patients were treated with BVP. The New York Heart Association functional class, LV ejection fraction, LV end-systolic volume, and B-type natriuretic peptide level improved in patients treated with HBP and BVP (all P< 0.05 vs baseline). Patients treated with HBP exhibited earlier and greater improvements of the LV ejection fraction and LV end-systolic volume than did those with BVP. HBP improves systolic function and LV relaxation in patients with HF and LBBB. CRT via HBP produced earlier and greater clinical responses than BVP.

Influence of Left Ventricular Function on the "Aortic Regurgitation Index" Proposed for the Hemodynamic Assessment of Postprocedural Aortic Regurgitation.

The aortic regurgitation (AR) index, proposed as an objective indicator of postprocedural AR, decreases in proportion to AR severity, besides reportedly providing additional prognostic information. Meanwhile, left ventricular (LV) function has also been considered an essential prognostic factor. This study aimed to clarify whether LV function affected the AR index using cardiac catheterization data.A retrospective study was performed in patients whose LV function was evaluated using a micromanometer-tipped catheter. Patients with grade 2 or higher AR were excluded to explore non-AR factors affecting the AR index value. The AR index was calculated as a ratio of the gradient between the aortic diastolic blood pressure (DBP) and the LV end-diastolic pressure (EDP) to the aortic systolic blood pressure (SBP): AR Index = [ (DBP - LVEDP) / SBP] × 100.A total of 64 patients [age, 62 (interquartile range: 48-70) years; LV ejection fraction, 19% (16%-26%) ] were examined. AR index values ranged from 18.3 to 68.6. Despite having no AR, two patients displayed an AR index < 25, indicating significant AR. Multiple-regression analysis revealed that LV diastolic stiffness (β = -0.750, P < 0.001), LV max dP/dt (β = -0.296, P = 0.006), and heart rate (β = 0.284, P = 0.011) were independent determinants of the AR index value.Patients with impaired LV diastolic function and preserved systolic function had low AR index values. The additional prognostic information of the AR index may be related to LV diastolic function.

Non-Invasive Estimation of Left Ventricular Filling Pressure Based on Left Atrial Area Strain Measured With Transthoracic 3-Dimensional Speckle Tracking Echocardiography in Patients With Coronary Artery Disease.

Background: Chronic elevation of left ventricular (LV) diastolic pressure (DP) or chronic elevation of left atrial (LA) pressure, which is required to maintain LV filling, may determine LA wall deformation. We investigated this issue using transthoracic 3-dimensional speckle tracking echocardiography (3D-STE).Methods and Results: We retrospectively enrolled 75 consecutive patients with sinus rhythm and suspected stable coronary artery disease who underwent diagnostic cardiac catheterization and 3D-STE on the same day. We computed the global LA wall area change ratio, termed the global LA area strain (GLAS), during both the reservoir phase (GLAS-r) and contraction phase (GLAS-ct). The LVDP at end-diastole (LVEDP) and mean LVDP (mLVDP) were measured with a catheter-tipped micromanometer in each patient. GLAS-r and GLAS-ct were significantly correlated with both mLVDP (r=−0.70 [P<0.001] and r=0.71 [P<0.001], respectively) and LVEDP (r=−0.63 [P<0.001] and r=0.65 [P<0.001], respectively). In receiver operating characteristic curve analysis, the optimal cut-off values for diagnosing elevated LVEDP (≥16 mmHg) were 75.7% (sensitivity 83.3%, specificity 77.8%) for GLAS-r and −43.1% (sensitivity 90.0%, specificity 80.0%) for GLAS-ct. Similarly, for diagnosing elevated mLVDP (≥12 mmHg), the cut-off values were 63.6% (sensitivity 88.9%, specificity 80.3%) for GLAS-r and −26.2% (sensitivity 66.7%, specificity 97.0%) for GLAS-ct.Conclusions: We showed that 3D-STE-derived GLAS values could be used to non-invasively diagnose elevated LV filling pressure.

Correlation Between Longitudinal Strain in the Apical Segments of the Left Ventricle at End-Systole Obtained by 2-Dimensional Speckle-Tracking Echocardiography and Left Ventricular Relaxation.

It is well acknowledged that left ventricular (LV) contractile performance affects LV relaxation via LV elastic recoil. Accordingly, we aimed to investigate whether global longitudinal strain (GLS), particularly longitudinal strain at LV apical segments at end-systole (ALS), obtained by 2-dimensional speckle-tracking echocardiography could be used to assess LV relaxation. We enrolled 121 patients with suspected or definite coronary artery disease in whom echocardiography and diagnostic cardiac catheterization were performed on the same day. We obtained conventional echo-Doppler parameters and GLS, as well as ALS prior to catheterization. LV functional parameters were obtained from the LV pressure recorded using a catheter-tipped micromanometer. In all patients, GLS and ALS were significantly correlated with the time constant τ of LV pressure decay during isovolumetric relaxation (r=0.63 [P<0.001] and r=0.66 [P<0.001], respectively). Receiver operating characteristic curve analysis for identifying impaired LV relaxation (τ ≥48 ms) revealed that ALS greater than -22.3% was an optimal cut-off value, with 81.7% sensitivity and 82.4% specificity. Even in patients with preserved LV ejection fraction, the same ALS cut-off value enabled the identification of impaired LV relaxation with 70% sensitivity and 87.5% specificity. The findings indicate that contractile dysfunction at LV apical segments slows LV relaxation via loss of LV elastic recoil, even in patients with preserved LVEF.

Left Ventricular End-Systolic Volume Is a Reliable Predictor of New-Onset Heart Failure with Preserved Left Ventricular Ejection Fraction.

Background Left ventricular (LV) ejection fraction (EF) and LV volumes were reported to have prognostic efficacy in cardiac diseases. In particular, the end-systolic volume index (LVESVI) has been featured as the most reliable prognostic indicator. However, such efficacy in patients with LVEF ≥ 50% has not been elucidated. Methods We screened the patients who received cardiac catheterization to evaluate coronary artery disease concomitantly with both left ventriculography and LV pressure recording using a catheter-tipped micromanometer and finally enrolled 355 patients with LVEF ≥ 50% and no history of heart failure (HF) after exclusion of the patients with severe coronary artery stenosis requiring early revascularization. Cardiovascular death or hospitalization for HF was defined as adverse events. The prognostic value of LVESVI was investigated using a Cox proportional hazards model. Results A univariable analysis demonstrated that age, log BNP level, tau, peak − dP/dt, LVEF, LV end-diastolic volume index (LVEDVI), and LVESVI were associated with adverse events. A correlation analysis revealed that LVESVI was significantly associated with log BNP level (r = 0.356, p < 0.001), +dP/dt (r = −0.324, p < 0.001), −dP/dt (r = 0.391, p < 0.001), and tau (r = 0.337, p < 0.001). Multivariable analysis with a stepwise procedure using the variables with statistical significance in the univariable analysis revealed that aging, an increase in BNP level, and enlargement of LVESVI were significant prognostic indicators (age: HR: 1.071, 95% CI: 1.009–1.137, p=0.024; log BNP : HR : 1.533, 95% CI: 1.090–2.156, p=0.014; LVESVI : HR : 1.051, 95% CI: 1.011–1.093, p=0.013, respectively). According to the receiver-operating characteristic curve analysis for adverse events, log BNP level of 3.23 pg/ml (BNP level: 25.3 pg/ml) and an LVESVI of 24.1 ml/m2 were optimal cutoff values (BNP : AUC : 0.753, p < 0.001, LVESVI : AUC : 0.729, p < 0.001, respectively). Conclusion In patients with LVEF ≥ 50%, an increased LVESVI is related to the adverse events. LV contractile performance even in the range of preserved LVEF should be considered as a role of a prognostic indicator.

Left ventricular contractile performance and heart failure in patients with left ventricular ejection fraction more than 40%

Heart failure (HF) with mid-range left ventricular ejection fraction (LVEF) (HFmrEF) is considered a new category of HF and LVEF < 50%, which is the upper threshold of LVEF for HFmrEF, is thought to represent a mild decrease in LV contractile performance. We aimed to consider an LVEF threshold value to be taken as a surrogate for impairment of LV contractile performance, resulting in new-onset HF. We enrolled 398 patients with LVEF ≥ 40% that underwent cardiac catheterization. Using the LV pressure recording with a catheter-tipped micromanometer, we calculated the inertia force of late systolic aortic flow (IFLSAF), which was sensitive to the slight impairment in LV contractile performance. We evaluated the utility of the IFLSAF for predicting future cardiovascular death or hospitalization for HF. We performed a receiver operating characteristic (ROC) curve analysis to determine the best LVEF threshold value for distinguishing whether the LV maintained the IFLSAF. A multivariate Cox proportional-hazards model revealed that the loss of IFLSAF was significantly associated with the future adverse events (HR: 7.798, 95%CI 2.174–27.969, p = 0.002). According to the ROC curve analysis, an LVEF ≥ 58% indicated that the LV could maintain the IFLSAF. We concluded that the loss of IFLSAF, which could reflect even slight impairment in LV contractile performance, was a reliable indicator for new-onset HF in patients with LVEF ≥ 40%. LVEF ≥ 58% could be taken as a surrogate for the IFLSAF maintenance; this threshold could be useful for risk stratification of new-onset HF in patients with preserved LVEF.

Different contributions from lungs and chest wall to respiratory mechanics in mice, rats, and rabbits.

Changes in lung mechanics are frequently inferred from intact-chest measures of total respiratory system mechanics without consideration of the chest wall contribution. The participation of lungs and chest wall in respiratory mechanics has not been evaluated systematically in small animals commonly used in respiratory research. Thus, we compared these contributions in intact-chest mice, rats, and rabbits and further characterized the influence of positive end-expiratory pressure (PEEP). Forced oscillation technique was applied to anesthetized mechanically ventilated healthy animals to obtain total respiratory system impedance (Zrs) at 0, 3, and 6 cmH2O PEEP levels. Esophageal pressure was measured by a catheter-tip micromanometer to separate Zrs into pulmonary (ZL) and chest wall (Zcw) components. A model containing a frequency-independent Newtonian resistance (RN), inertance, and a constant-phase tissue damping (G) and elastance (H) was fitted to Zrs, ZL, and Zcw spectra. The contribution of Zcw to RN was negligible in all species and PEEP levels studied. However, the participation of Zcw in G and H was significant in all species and increased significantly with increasing PEEP and animal size (rabbit > rat > mice). Even in mice, the chest wall contribution to G and H was still considerable, reaching 47.0 ± 4.0(SE)% and 32.9 ± 5.9% for G and H, respectively. These findings demonstrate that airway parameters can be assessed from respiratory system mechanical measurements. However, the contribution from the chest wall should be considered when intact-chest measurements are used to estimate lung parenchymal mechanics in small laboratory models (even in mice), particularly at elevated PEEP levels. NEW & NOTEWORTHY In species commonly used in respiratory research (rabbits, rats, mice), esophageal pressure-based estimates revealed negligible contribution from the chest wall to the Newtonian resistance. Conversely, chest wall participation in the viscoelastic tissue mechanical parameters increased with body size (rabbit > rat > mice) and positive end-expiratory pressure, with contribution varying between 30 and 50%, even in mice. These findings demonstrate the potential biasing effects of the chest wall when lung tissue mechanics are inferred from intact-chest measurements in small laboratory animals.

Abstract 324: An Engineered Protein as an Antidote for Carbon Monoxide Poisoning That Can Reverse Cardiovascular Collapse Through Scavenging of Carbon Monoxide and Rescue of Mitochondrial Respiration

Background: Carbon monoxide (CO) is the most common human poisoning. There is no antidote. One-third of hospitalized patients will have cardiac dysfunction and increased mortality. Little is known about the nature of cardiovascular dysfunction during acute CO poisoning. CO toxicity results from: (1) global hypoxia and decreased oxygen delivery through CO binding to hemoglobin, (2) inhibition of oxidative phosphorylation from CO binding to cytochrome c oxidase, and (3) ensuing superoxide injury. We have developed a recombinant neuroglobin molecule (rNgb) with a high affinity for CO, that can chelate CO from intrinsic heme proteins. Hypothesis: The addition of rNgb will scavenge CO from hemoglobin and cytochrome c oxidase, reversing CO-induced cardiovascular dysfunction. Methods: We inserted micromanometer-tip catheters into the left ventricle of ventilated, severely CO poisoned mice to study the mechanisms of CO-induced cardiovascular collapse. In a similar model, we measured blood pressure and heart rate of severely CO poisoned, ventilated mice through a carotid arterial catheter and treated with phosphate buffered saline (PBS) or rNgb. Hearts were isolated from these mice and we measured tissue respiration using a Clark-type oxygen electrode. We compared the respiration rates of these animals and compared with non-poisoned, sedated control mice. We also compared the enzymatic activity of electron transport chain complexes. Results and Conclusions: When compared to control mice (exposed to 21% oxygen/no CO), CO poisoned mice develop a decreased contractility index (-32.3% baseline vs. -10.8% in control, t-test, p=0.002), hypotension and death, indicating primary cardiac toxicity. CO-poisoned mice treated with PBS had heart tissue respiration that was 62.3% (+/- 7.5%) of sedated control mice (t-test, P=0.015). Treatment of mice with rNgb restored tissue respiration (P=0.037 versus PBS treated mice) similar to control values. CO poisoning reduced the activity level of complex IV in PBS treated mice (P=0.011), but levels were similar to control in rNgb treated mice. These molecular changes were associated with reversal of cardiovascular collapse in rNgb treated mice versus PBS, demonstrating the potential of rNgb as a CO poisoning antidote.

Left Ventricular Mass Influences Relationship Between Filling Pressure and Early-Diastolic Ratio of Inflow Velocity to Mitral Annular Velocity (E/e').

Early-diastolic mitral annular velocity (e') and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e' (E/e') have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study. The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e' only weakly correlated with τ (r=-0.35, P<0.01), E/e' modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension (β=-0.33, P<0.01) and LV ejection fraction (LVEF) (β=0.44, P<0.001) were the independent determinants of e', and LV mass index (LVMI) (β=0.37, P<0.001) and LVMDP (β=0.47, P<0.001) were those of E/e'. Additionally, E/e' significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI. The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e', whereas LVMI altered the relationship between LV filling pressure and E/e'. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e'.

YIA-CS1-6 - Importance of Left Ventricular End-systolic Volume Index as a Prognostic Indicator in Heart Failure with Preserved Left Ventricular Ejection Fraction

Background: A prognostic efficacy of Left ventricular ejection fraction (LVEF) in heart failure with preserved LVEF (HFpEF) is unclear. Methods: We enrolled 471 patients (LVEF>&=50%) who received a catheterization study and obtained baseline characteristics including LVEF, LV end-diastolic and end-systolic volume indices (LVEDVI, LVESVI) which were measured by left ventriculography. Pressure parameters such as tau, and inertia force of late systolic aortic flow (IFLAF) were also obtained using a catheter-tipped micro-manometer. Cardiovascular death or hospitalization for HF were defined as adverse events, and prognostic values of parameters were estimated using a Cox proportional-hazard model. In addition, we compared the prognostic efficacy and correlations with pressure parameters between LVEF, LVESVI, and LVEDVI. Results: During 6.61 ± 4.08 year-follow-up, 39 adverse events were documented. The Cox model after adjustments for age, gender, and hemoglobin level demonstrated that 3 parameters had a significant prognostic value for adverse events (LVEF: HR: 0.951, 95%CI: 0.916–0.987, P = .008; LVEDVI: HR: 1.033, 95%CI: 1.017–1.049, P < .001; LVESVI: HR: 1.049, 95%CI: 1.025–1.074, P < .001) According to the comparison of AUC in the 3 parameters, the LVESVI was most accurate (AUC: 0.694, 0.351 (LVEF), 0.661 (LVEDVI)). Furthermore, the LVESVI demonstrated the strongest correlations with tau (r = 0.364, -0.284 (LVEF), 0.330 (LVEDVI)) and IFLAF (r=-0.358, 0.320 (LVEF), -0.277 (LVEDVI)) in the 3 parameters. Conclusion: Enlargement of LVESVI could be a reliable prognostic indicator in HFpEF.

YIA-CS1-4 - Loss of Inertia Force of Late-systolic Aortic Flow in Patients with Mid-range Left Ventricular Ejection Fraction Deterioration

Background: The upper limit of cut-off value of left ventricular ejection fraction (LVEF) for classifying heart failure with mid-range deterioration of LVEF (HFmrEF) is unclear. Methods: The cardiac functional parameters of study patients (n = 428, LVEF>&=40%) including inertia force of late systolic aortic flow (IFLAF) which was calculated from the LV pressure and dP/dt relation were obtained using a catheter-tipped micro-manometer. We determined a cut-off value of LVEF to divide the patients into 2 groups where they had different cardiac functional backgrounds. We then searched a predictor of future cardiovascular death or hospitalization for HF in each group. In addition, we determined an appropriate upper limit LVEF level of the HFmrEF based on the predictor using ROC analysis. Results: Significant differences in tau, ±dP/dt, and IFLAF were demonstrated between patients with LVEF <60% and >&=60%. In patients with LVEF <60%, a multivariate Cox proportional-hazards model revealed that a loss of IFLAF was a significant predictor of future events (HR: 0.222, 95%CI: 0.049 to 0.996, P=.049). Furthermore, an LVEF <58% was a surrogate indicator for loss of IFLAF and a time-dependent ROC analysis revealed that the IFLAF could be a strong predictor with a high accuracy among patients with LVEF up to 67%. Conclusion: Maintaining systolic function with the existence of IFLAF may be a key issue for preventing HFpEF.

Veno-venous extracorporeal CO2 removal improves pulmonary hemodynamics in a porcine ARDS model.

Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ventilation at lower tidal volume enhances pulmonary hypertension and might induce right ventricular (RV) failure. We investigated if extracorporeal veno-venous CO2 removal therapy could have beneficial effects on pulmonary circulation and RV function. This study was performed on an experimental model of ARDS obtained in eight anaesthetized pigs connected to a volume-cycled ventilator. A micromanometer-tipped catheter was inserted into the main pulmonary artery and an admittance micromanometer-tipped catheter was inserted into the right ventricle. RV-arterial coupling was derived from RV pressure-volume loops. ARDS was obtained by repeated bronchoalveolar lavage. Protective ventilation was then achieved, and the pigs were connected to a pump-driven extracorporeal membrane oxygenator (PALP, Maquet, Germany) in order to achieve CO2 removal. ARDS induced severe hypercapnic acidosis. Systolic pulmonary artery pressure significantly increased from 29.6±1.8 to 43.9±2.0 mmHg (P<0.001). After the PALP was started, acidosis was corrected and normocarbia was maintained despite protective ventilation. Pulmonary artery pressure significantly decreased to 31.6±3.2 mmHg (P<0.001) and RV-arterial coupling significantly improved (RV-arterial coupling index=1.03±0.33 vs. 0.55±0.41, P<0.05). Veno-venous CO2 removal therapy enabled protective ventilation while maintaining normocarbia during ARDS. CO2 removal decreased pulmonary hypertension and improved RV function. This technique may be an effective lung- and RV-protective adjunct to mechanical ventilation.

Compensatory increase of left atrial external work to left ventricular dysfunction caused by afterload increase.

Afterload mismatch can cause acute decompensation leading to an occurrence of acute heart failure. We investigated how the left atrium (LA) and left ventricle (LV) react to acute increases in afterload using speckle tracking echocardiography (STE). LA strain and volume were obtained by STE in 10 dogs during banding of descending aorta (AoB). Simultaneously, LA pressure was measured by a micromanometer-tipped catheter. LA peak negative strain during LA contraction, strain change during LA relaxation (early reservoir strain), and that during LA dilatation (late reservoir strain) were obtained from LA longitudinal strain-volume curves. From pressure-strain curves, the areas of A-loop and V-loops were computed as the work during active contraction and relaxation (A-work) and that during passive filling and emptying (V-work). AoB increased LV systolic pressure (105 ± 15 vs. 163 ± 12 mmHg, P < 0.01) and mean LA pressure (3.8 ± 1.2 vs. 7.1 ± 2.0 mmHg, P < 0.01). LV global circumferential strain decreased (-18.8 ± 3.5 vs. -13.2 ± 3.5%, P < 0.01), but LV stroke volume was maintained (8.4 ± 2.3 vs. 9.6 ± 3.6 ml). LA peak negative strain (-2.9 ± 2.3 vs. -9.8 ± 4.0%, P < 0.01) and early reservoir strain (4.5 ± 2.1 vs. 7.7 ± 2.4%, P < 0.05) increased by AoB, but late reservoir strain did not change (8.9 ± 3.4 vs. 6.1 ± 3.4%). A-work significantly increased (3.2 ± 2.0 vs. 19.2 ± 15.1 mmHg %, P < 0.01), whereas V-work did not change (13.3 ± 7.1 vs. 13.1 ± 7.7 mmHg %). In conclusion, LA external work during active contraction and relaxation increased as compensation for LV dysfunction during aortic banding. Atrial dysfunction may lead failure of this mechanism and hemodynamic decompensation.