Assessment of Early Diastolic Intraventricular Pressure Difference in Children by Blood Speckle-Tracking Echocardiography.

BACKGROUND: The lack of reliable echocardiographic techniques to assess diastolic function in children is a major clinical limitation. Our aim was to develop and validate the intraventricular pressure difference (IVPD) calculation using blood speckle-tracking (BST) and investigate the method's potential role in the assessment of diastolic function in children. METHODS: Blood speckle-tracking allows two-dimensional angle-independent blood flow velocity estimation. Blood speckle-tracking images of left ventricular (LV) inflow from the apical 4-chamber view in 138 controls, 10 patients with dilated cardiomyopathies (DCMs), and 21 patients with hypertrophic cardiomyopathies (HCMs) <18 years of age were analyzed to study LV IVPD during early diastole. Reproducibility of the IVPD analysis was assessed, IVPD estimates from BST and color M mode were compared, and the validity of the BST-based IVPD calculations was tested in a computer flow model. RESULTS: Mean IVPD was significantly higher in controls (-2.28 ± 0.62 mm Hg) compared with in DCM (-1.21 ± 0.39 mm Hg, P < .001) and HCM (-1.57 ± 0.47 mm Hg, P < .001) patients. Feasibility was 88.3% in controls, 80% in DCM patients, and 90.4% in HCM patients. The peak relative negative pressure occurred earlier at the apex than at the base and preceded the peak E-wave LV filling velocity, indicating that it represents diastolic suction. Intraclass correlation coefficients for intra- and interobserver variability were 0.908 and 0.702, respectively. There was a nonsignificant mean difference of 0.15 mm Hg between IVPD from BST and color M mode. Estimation from two-dimensional velocities revealed a difference in peak IVPD of 0.12 mm Hg (6.6%) when simulated in a three-dimensional fluid mechanics model. CONCLUSIONS: Intraventricular pressure difference calculation from BST is highly feasible and provides information on diastolic suction and early filling in children with heart disease. Intraventricular pressure difference was significantly reduced in children with DCM and HCM compared with controls, indicating reduced early diastolic suction in these patient groups.

Non-invasive assessment of left ventricular relaxation property using color M-mode-derived intraventricular pressure gradients in cats.

INTRODUCTION: Diastolic dysfunction is an early clinical feature of feline hypertrophic cardiomyopathy (HCM). The left ventricular filling in early diastole is facilitated by the diastolic intraventricular pressure gradient (IVPG). The study objectives were to evaluate color Doppler M-mode-derived IVPG calculation in cats as a non-invasive assessment of the left ventricular relaxation property to determine the normal ranges of peak IVPG in cats and investigate the influence of left ventricular function and heart rate (HR). ANIMALS: One hundred and six client-owned apparently healthy cats. METHODS: Prospective cross-sectional study. Quantitative analysis of color Doppler M-mode images was used to estimate total and segmental IVPGs non-invasively. RESULTS: The total IVPG was 0.76 mmHg (95% reference interval (RI): 0.28-1.29 mmHg), the basal IVPG 0.34 mmHg (95% RI: 0.07-0.63 mmHg), and the mid-apical IVPG 0.42 mmHg (95% RI: 0.15-0.71 mmHg). Total and segmental IVPG increased with HR (P < 0.003), while segmental percent IVPG was HR independent. A short isovolumic relaxation time (IVRT) and a high mitral annular velocity in early diastole were associated with an increase in total IVPG (P = 0.008 and P = 0.009, respectively) adjusted for HR. An increase in IVPG was associated with an increase in mitral inflow velocity (P < 0.001). CONCLUSIONS: Feline IVPGs increase with HR and a short IVRT, which was believed to be a normal physiologic adrenergic response associated with an increased sympathetic tone. Future studies of segmental IVPG changes in feline HCM are needed to evaluate the clinical applicability of color Doppler M-mode estimated IVPGs in feline cardiology.

Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure-volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end-systolic pressure-volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end-systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular-arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow-limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST-segment depression on exercise); five patients without flow-limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow-limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.

An exploratory assessment of stretch-induced transmural myocardial fiber kinematics in right ventricular pressure overload.

Right ventricular (RV) remodeling and longitudinal fiber reorientation in the setting of pulmonary hypertension (PH) affects ventricular structure and function, eventually leading to RV failure. Characterizing the kinematics of myocardial fibers helps better understanding the underlying mechanisms of fiber realignment in PH. In the current work, high-frequency ultrasound imaging and structurally-informed finite element (FE) models were employed for an exploratory evaluation of the stretch-induced kinematics of RV fibers. Image-based experimental evaluation of fiber kinematics in porcine myocardium revealed the capability of affine assumptions to effectively approximate myofiber realignment in the RV free wall. The developed imaging framework provides a noninvasive modality to quantify transmural RV myofiber kinematics in large animal models. FE modeling results demonstrated that chronic pressure overload, but not solely an acute rise in pressures, results in kinematic shift of RV fibers towards the longitudinal direction. Additionally, FE simulations suggest a potential protective role for concentric hypertrophy (increased wall thickness) against fiber reorientation, while eccentric hypertrophy (RV dilation) resulted in longitudinal fiber realignment. Our study improves the current understanding of the role of different remodeling events involved in transmural myofiber reorientation in PH. Future experimentations are warranted to test the model-generated hypotheses.

Noninvasive assessment of intraventricular pressure difference in left ventricular dyssynchrony using vector flow mapping.

Diastolic intraventricular pressure difference (IVPD) reflects left ventricular (LV) diastolic function. The relative pressure imaging (RPI) enables the noninvasive quantification of IVPD based on vector flow mapping (VFM) and visualization of regional pressure distribution. LV dyssynchrony causes deterioration of cardiac performance. However, it remains unclear how IVPD is modulated by LV dyssynchrony. LV dyssynchrony was created in ten open-chest dogs by right ventricular (RV) pacing. The other ten dogs undergoing right atrial (RA) pacing set at the similar heart rate with RV pacing were used as controls. Echocardiographic images were acquired at baseline and during pacing simultaneously with LV pressure measurement by a micromanometer. Pressure difference (ΔP) was computed between the apex and the base of the LV inflow tract during a cardiac cycle by RPI and ΔP during isovolumic relaxation time (ΔPIRT), a parameter of diastolic suction, and that during early filling phase (ΔPE) were measured. During RV pacing, stroke volume (SV) and ΔPIRT decreased significantly, while ΔPE did not change compared to the baseline. During RA pacing, SV, ΔPIRT and ΔPE did not change significantly. ΔPIRT tended to correlate with -dP/dtmin and end-systolic volume, and significantly correlated with ejection fraction. IVPD during isovolumic relaxation time was decreased by LV dyssynchrony, while IVPD during early filling phase was not. A reduction of diastolic suction is observed in LV dyssynchrony and is significantly related to a decrease in SV.

Model-based estimation of left ventricular pressure and myocardial work in aortic stenosis.

This paper proposes a model-based estimation of left ventricular (LV) pressure for the evaluation of constructive and wasted myocardial work of patients with aortic stenosis (AS). A model of the cardiovascular system is proposed, including descriptions of i) cardiac electrical activity, ii) elastance-based cardiac cavities, iii) systemic and pulmonary circulations and iv) heart valves. After a sensitivity analysis of model parameters, an identification strategy was implemented using a Monte-Carlo cross-validation approach. Parameter identification procedure consists in two steps for the estimation of LV pressures: step 1) from invasive, intraventricular measurements and step 2) from non-invasive data. The proposed approach was validated on data obtained from 12 patients with AS. The total relative errors between estimated and measured pressures were on average 11.9% and 12.27% and mean R2 were equal to 0.96 and 0.91, respectively for steps 1 and 2 of parameter identification strategy. Using LV pressures obtained from non-invasive measurements (step 2) and patient-specific simulations, Global Constructive (GCW), Wasted (GWW) myocardial Work and Global Work Efficiency (GWE) parameters were calculated. Correlations between measures and model-based estimations were 0.88, 0.80, 0.91 respectively for GCW, GWW and GWE. The main contributions concern the proposal of the parameter identification procedure, applied on an integrated cardiovascular model, able to reproduce LV pressure specifically to each AS patient, by non-invasive procedures, as well as a new method for the non-invasive estimation of constructive, wasted myocardial work and work efficiency in AS.

The assessment of pressure-volume relationship during exercise stress echocardiography predicts left ventricular remodeling and eccentric hypertrophy in patients with chronic heart failure.

BACKGROUND: The contractile response of patients with heart failure (HF) may be assessed by exercise stress echocardiography (ESE)-derived indexes. We sought to test whether ESE parameters are useful to identify the risk of adverse left ventricular (LV) remodeling in patients with chronic HF and reduced or mildly reduced LV ejection fraction (EF). METHODS: We enrolled 155 stabilized patients (age: 62 ± 11 years, 17% female, coronary artery disease 47%) with chronic HF, LV EF ≤50% and LV end-diastolic volume index > 75 ml/m2. All patients underwent a symptom-limited graded bicycle semi-supine ESE, with evaluation of peak stress LV EF, end-systolic pressure-volume relation (ESPVR, i.e. LV elastance) and cardiac power output to LV mass (CPOM). A complete echocardiographic study was performed at baseline and after 6 ± 3 months. Adverse LV remodeling was defined as the association of eccentric LV hypertrophy (LV mass: ≥115 g/m2 for male and ≥ 95 g/m2 for women, and relative wall thickness < 0.32) with an increase in LV end-systolic volume index ≥10% at six months. RESULTS: Adverse LV remodeling was detected in 34 (22%) patients. After adjustment for clinical, biochemical and echocardiographic data, peak ESPVR resulted in the most powerful independent predictor of adverse LV remodeling (OR: 12.5 [95% CI 4.5-33]; p < 0.0001) followed by ischemic aetiology (OR: 2.64 [95% 1.04-6.73]; p = 0.04). CONCLUSION: In patients with HF and reduced or mildly reduced EF, a compromised ESE-derived peak ESPVR, that reflects impaired LV contractility, resulted to be the most powerful predictor of adverse LV remodeling.

Echocardiography-based pressure-volume loop assessment in the evaluation for the effects of indoxyl sulfate on cardiovascular function.

BACKGROUND: Indoxyl sulfate (IS), a uremic toxin, has been reported to have hypertrophic effects on the heart. Previous studies, however, have shown no association between elevated IS levels and cardiovascular outcomes in hemodialysis patients. We hypothesized that, despite left ventricular (LV) hypertrophy, myocardial contractility and ventricular-arterial coupling would remain preserved, and that this would explain the reason for the absence of prognostic impact of IS. METHODS: We evaluated the association of IS with LV structure, contractility, vascular function, and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) in 154 patients on hemodialysis, using echocardiography-based pressure-volume loop assessment. RESULTS: As expected, subjects in the high IS group (IS ≥ 33.8 µg/mL) had greater LV mass index and end-diastolic volume index compared to subjects in the low IS group (IS < 33.8 µg/mL). These differences remained significant after adjusting for age, sex, body mass index, diabetic nephropathy, duration of hemodialysis, and NT-proBNP levels, suggesting a potential role of elevated IS levels in LV remodeling. However, no differences in LV contractility (preload recruitable stroke work, peak power index, and systolic mitral annular velocity) and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) were observed between the groups. CONCLUSIONS: Deleterious effects of IS on LV remodeling are not accompanied by impaired LV contractility or mechanical efficiency, which could contribute to the absence of cardiovascular prognostic impact observed in previous studies performed on hemodialysis patients.

Echo-Doppler assessment of ventricular filling pressures in adult Fontan patients.

BACKGROUND: Diastolic dysfunction is felt to be part of the natural history of patients with prior Fontan operation. Despite that, data on noninvasive assessment of diastolic function and ventricular filling pressures in Fontan patients are limited. METHODS: We included 45 adult Fontan patients who underwent right heart catheterization with pulmonary artery wedge pressure (PAWP) measurement and transthoracic echo-Doppler assessment within 7 days. Offline measurement of systemic atrioventricular valve pulsed-wave (PW) and medial/lateral atrioventricular annular tissue Doppler velocities was performed and correlated to PAWP. RESULTS: Median age was 31.4 years (IQR 24.8-37); 51% of patients were females. Median ventricular ejection fraction was 55% (IQR 50.3-57.5) and median PAWP was 10 mm Hg (IQR 8-11). PW Doppler E velocity (r = 0.64, p ≤ 0.0001), deceleration time (r = -0.40, p = 0.008), and E/A ratio (r = 0.33, p = 0.03) correlated with PAWP. Median medial and lateral E/e' ratios also correlated to PAWP (r = 0.71, p = 0.002 and r = 0.75, p < 0.0001; respectively). An E velocity >75 cm/s had 88% sensitivity and 86% specificity [97% negative predictive value (NPV); 58% positive predictive value (PPV)], E/A ratio >1.7 had 100% sensitivity and 61% specificity (100% NPV; 26% PPV), and deceleration time <135 ms had 88% sensitivity and 83% specificity (97% NPV; 58% PPV) for predicting PAWP >12 mm Hg. CONCLUSION: Our data suggest that PW Doppler atrioventricular E velocity, E/A ratio, and deceleration time could be used to identify adult Fontan patients with normal filling pressures. However, PPVs for PAWP >12 mm Hg were poor. Further studies, particularly prospective, simultaneous echo-catheterization correlation, are critically needed.

Improving the echocardiographic assessment of pulmonary pressure using the tricuspid regurgitant signal-The "chin" vs the "beard".

AIM: Transthoracic echocardiography (TTE) is a fundamental investigation for the noninvasive assessment of pulmonary hemodynamics and right heart function. The aim of this study was to assess the correlation and agreement of Doppler calculation of right ventricular systolic pressure (RVSP) and pulmonary vascular resistance (PVR) using "chin" and "beard" measurements of tricuspid regurgitant velocity (TRVmax ), with invasive pulmonary artery systolic pressure (PASP) and PVR. METHODS: One hundred patients undergoing right heart catheterisation (RHC) and near simultaneous transthoracic echocardiography were studied. TRVmax was recorded for "chin" measurement (distinct peak TRVmax signal) and where available (63 patients), "beard" measurement (higher indistinct peak TRVmax signal). RESULTS: Measurable TRV signal was obtained in 96 patients. Mean RVSPchin 54.7 ± 22.7 mm Hg and RVSPbeard 68.6 = 23 ± 26.3 mm Hg (P < .001). There was strong correlation between both RVSPchin and RVSPbeard with invasive PASP (Pearson's r = .9, R2  = 0.82, P < .001 - r = .88, R = .78, P < .001, respectively.). Bland-Altman analysis for RVSPchin and RVSPbeard showed a mean bias of -0.5 mm Hg (95% limits of agreement -21.4 to 20.5 mm Hg) and -10.7 (95% LOA -35.5 to 14.2 mm Hg), respectively. Receiver operator characteristics of TRVmax "chin" and "beard" for diagnosis of pulmonary hypertension was assessed with optimal cut-offs being 2.8 m/s (sensitivity 93%, specificity 87%) and 3.2 m/s (sensitivity 91%, specificity 82%), respectively. There was similar correlation between PVRchin and PVRbeard (r = .87, R2  = 0.75, P < .001 and r = .86, R2  = 0.74, P < .001, respectively). At higher PVR, there was overestimation of calculated PVR using PVRbeard . CONCLUSION: The accuracy of noninvasive measurement of right heart pressures is increased using the "chin" in estimation of both RVSP and PVR.

Assessment of early treatment response by rapid cardiothoracic ultrasound in acute heart failure: Cardiac filling pressures, pulmonary congestion and mortality.

BACKGROUND: It is unclear how to optimally monitor acute heart failure (AHF) patients. We evaluated the timely interplay of cardiac filling pressures, brain natriuretic peptides (BNPs), lung ultrasound (LUS) and symptoms during AHF treatment. METHODS: We enrolled 60 patients who had been hospitalised for AHF. Patients were examined with a rapid cardiothoracic ultrasound (CaTUS) protocol, combining LUS and focused echocardiographic evaluation of cardiac filling pressures (i.e. medial E/e' and inferior vena cava index [IVCi]). CaTUS was done at 0, 12, 24 and 48 hours (±3 hours) and on the day of discharge, alongside clinical evaluation and laboratory samples. Patients free of congestion (B lines or pleural fluid) on LUS at discharge were categorised as responders, whereas the rest were categorised as non-responders. Improvement in congestion parameters was evaluated separately in these groups. The effect of congestion parameters on prognosis was also analysed. RESULTS: Responders experienced a significantly larger decline in E/e' (2.58 vs. 0.38, p = 0.037) and dyspnoea visual analogue scale (1-10) score (7.68 vs. 3.57, p = 0.007) during the first 12 hours of treatment, while IVCi and BNPs declined later without no such rapid initial decline. Among patients experiencing a >3 U decline in E/e' during the first 12 hours of treatment, 18/21 were to become responders ( p < 0.001). LUS response was the only congestion parameter independently predicting both 6-month survival regarding all-cause mortality and the composite endpoint of all-cause mortality or rehospitalisation for AHF. CONCLUSION: E/e' seemed like the most useful congestion parameter for monitoring early treatment response, predicting prognostically beneficial resolution of pulmonary congestion.

Assessment of methodologies to calculate intraventricular pressure differences in computational models and patients.

Intraventricular pressure differences (IVPDs) govern left ventricular (LV) efficient filling and are a significant determinant of LV diastolic function. Our primary aim is to assess the performance of available methods (color M-mode (CMM) and 1D/2D MRI-based methods) to determine IVPDs from intracardiac flow measurements. Performance of three methods to calculate IVPDs was first investigated via an LV computational fluid dynamics (CFD) model. CFD velocity data were derived along a modifiable scan line, mimicking ultrasound/MRI acquisition of 1D (IVPDCMM/IVPD1D MRI) and 2D (IVPD2D MRI) velocity-based IVPD information. CFD pressure data (IVPDCFD) was used as a ground truth. Methods were also compared in a small cohort (n = 13) of patients with heart failure with preserved ejection fraction (HFpEF). In silico data showed a better performance of the IVPD2D MRI approach: RMSE values for a well-aligned scan line were 0.2550 mmHg (IVPD1D MRI), 0.0798 mmHg (IVPD2D MRI), and 0.2633 mmHg (IVPDCMM). In vivo data exhibited moderate correlation between techniques. Considerable differences found may be attributable to different timing of measurements and/or integration path. CFD modeling demonstrated an advantage using 2D velocity information to compute IVPDs, and therefore, a 2D MRI-based method should be favored. However, further studies are needed to support the clinical significance of MRI-based computation of IVPDs over CMM.

Invasive Validation of the Echocardiographic Assessment of Left Ventricular Filling Pressures Using the 2016 Diastolic Guidelines: Head-to-Head Comparison with the 2009 Guidelines.

BACKGROUND: Recent American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines for echocardiographic evaluation of left ventricular (LV) diastolic function provide a practical, simplified diagnostic algorithm for estimating LV filling pressure. The aim of this study was to test the accuracy of this algorithm against invasively measured pressures and compare it with the accuracy of the previous 2009 guidelines in the same patient cohort. METHODS: Ninety patients underwent transthoracic echocardiography immediately before left heart catheterization. Mitral inflow E/A ratio, E/e', tricuspid regurgitation velocity, and left atrial volume index were used to estimate LV filling pressure as normal or elevated using the ASE/EACVI algorithm. Invasive LV pre-A pressure was used as a reference, with >12 mm Hg defined as elevated. RESULTS: Invasive LV pre-A pressure was elevated in 40 (44%) and normal in 50 (56%) patients. The 2016 algorithm resulted in classification of 9 of 90 patients (10%) as indeterminate but estimated LV filling pressures in agreement with the invasive reference in 61 of 81 patients (75%), with sensitivity of 0.69 and specificity of 0.81. The 2009 algorithm could not definitively classify 4 of 90 patients (4.4%), but estimated LV filling pressures in agreement with the invasive reference in 64 of 86 patients (74%), with sensitivity of 0.79 and specificity of 0.70. CONCLUSIONS: The 2016 ASE/EACVI guidelines for estimation of filling pressures are more user friendly and efficient than the 2009 guidelines and provide accurate estimates of LV filling pressure in the majority of patients when compared with invasive measurements. The simplicity of the new algorithm did not compromise its accuracy and is likely to encourage its incorporation into clinical decision making.

Non-invasive assessment of left ventricular filling pressure.

Dyspnoea is a presenting symptom for patients with heart failure. It is often due to elevated left ventricular (LV) filling pressure but can be due to pulmonary disease or other non-cardiac reasons. While physical examination is useful, it has its limitations. Accordingly, non-invasive imaging has an important role in the diagnostic evaluation of patients with known or suspected heart failure. Echocardiography is usually the first test obtained and is used to determine LV volumes, ejection fraction and mass as well as right ventricular size and function, left and right atrial volumes, valvular lesions, and pulmonary artery pressures. Additionally, LV filling pressure can be estimated. A recent algorithm was published that depends on clinical, two-dimensional data and Doppler signals. The algorithm is accurate in patients with depressed and normal ejection fraction. There are other measurements that can be obtained as LV strain and diastolic strain rate and left atrial strain. These indices provide valuable insight into LV relaxation and filling pressure as well as left atrial function. Assessment of LV filling pressure has been evaluated most extensively in patients in sinus rhythm. However, it is also possible to assess LV filling and draw inferences about LV filling pressure in patients in atrial fibrillation, in patients with mitral valve disease and in patients with left ventricular assist devices. Left ventricular filling has been assessed by other imaging modalities, including cardiac computed tomography and cardiac magnetic resonance. While these other imaging modalities may be needed in some cases, echocardiography has the highest feasibility and validation, and the most practical application.

Evaluation of left ventricular diastolic function: state of the art after 35 years with Doppler assessment.

Left ventricular (LV) diastolic function can be evaluated by echocardiographic indices of LV relaxation/restoring forces, diastolic compliance, and filling pressure. By using a combination of indices, diastolic function can be graded and LV filling pressure estimated with high feasibility and good accuracy. Evaluation of diastolic function is of particular importance in patients with unexplained exertional dyspnea or other symptoms or signs of heart failure which cannot be attributed to impaired LV systolic function and to assess filling pressure in patients with heart failure and reduced LV ejection fraction. Furthermore, grading of diastolic dysfunction can be used for risk assessment in asymptomatic subjects and in patients with heart disease.

Assessment of early diastolic intraventricular pressure gradient in the left ventricle among patients with repaired tetralogy of Fallot.

Assessment of left ventricular (LV) dysfunction is vital in patients with repaired tetralogy of Fallot (rTOF). The early diastolic intraventricular pressure gradient (IVPG) in the LV plays an important role in diastolic function. IVPG is calculated as the intraventricular pressure difference divided by the LV length, which allows to account for differences in LV size and therefore calculate IVPG in children. We aimed to investigate the mechanisms of LV diastolic dysfunction by measuring mid-to-apical IVPG as an indicator of the active suction force sucking blood from the left atrium into the LV. We included 38 rTOF patients and 101 healthy controls. The study population was stratified based on age group into children (4-9 years), adolescents (10-15 years), and adults (16-40 years). IVPGs were calculated based on mitral inflow measurements obtained using color M-mode Doppler echocardiography. Although total IVPGs did not differ between rTOF patients and controls, mid-to-apical IVPGs in adolescents and adults were smaller among rTOF patients than among controls (0.15 ± 0.05 vs. 0.21 ± 0.06 mmHg/cm, p < 0.05; 0.09 ± 0.07 vs. 0.17 ± 0.05 mmHg/cm, p < 0.001; respectively). Additionally, only mid-to-apical IVPG correlated linearly with peak circumferential strain (ρ = 0.217, p = 0.011), longitudinal strain (ρ = -0.231, p = 0.006), torsion (ρ = -0.200, p = 0.018), and untwisting rate in early diastole (ρ = -0.233, p = 0.006). In rTOF, the mechanisms underlying diastolic dysfunction involve reduced active suction force, which correlates with reduced LV deformation in all directions.

Promising approach for the preclinical assessment of cardiac risks using left ventricular pressure-volume loop analyses in anesthetized monkeys.

INTRODUCTION: Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy. In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dependent inotropic, hemodynamic and electrocardiographic changes in isoflurane-anesthetized monkeys. METHODS: The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a ß-blocker), or dl-sotalol (a ß+IKr blocker) intravenously over 10min at two dose levels including clinically relevant doses (n=5/drug). RESULTS: Milrinone and metoprolol produced positive and negative inotropy, respectively. These effects were detected as changes in the slope of the preload-recruitable stroke work, which is a load-independent inotropic parameter. However, dl-sotalol did not alter the slope of the preload-recruitable stroke work. That means dl-sotalol produced no inotropy, although it decreased load-dependent inotropic parameters, including maximal upstroke velocity of left ventricular pressure, attributable to decreased heart rate and blood pressure. Other typical pharmacological effects of the compounds tested were also detected. Both ß-blockers produced PR prolongation, decreased left ventricular end-systolic pressure, increased left ventricular end-diastolic pressure, and increased maximal descending velocity of left ventricular pressure and time constant for isovolumic relaxation. dl-Sotalol also prolonged heart-rate-corrected QT interval. Milrinone induced reflex tachycardia, PR shortening, and decreased left ventricular end-diastolic pressure. DISCUSSION: The overall assessment by not only load-dependent inotropic parameters but also load-independent parameters obtained from the ventricular pressure-volume loop analysis using monkeys can provide further appropriate information for the assessment of drug-induced cardiac risks.

MRI Assessment of Diastolic and Systolic Intraventricular Pressure Gradients in Heart Failure.

A deep phenotypic characterization of heart failure (HF) is important for a better understanding of its pathophysiology. In particular, novel noninvasive techniques for the characterization of functional abnormalities in HF with preserved ejection fraction are currently needed. While echocardiography is widely used to assess ventricular function, standard echocardiographic techniques provide a limited understanding of ventricular filling. The application of fluid dynamics theory, along with assessments of flow velocity fields in multiple dimensions in the ventricle, can be used to assess intraventricular pressure gradients (IVPGs), which in turn may provide valuable insights into ventricular diastolic and systolic function. Advances in imaging techniques now allow for accurate estimations of systolic and diastolic IVPGs, using noninvasive methods that are easily applicable in clinical research. In this review, we describe the basic concepts regarding intraventricular flow measurements and the derivation of IVPGs. We also review existing literature exploring the role of IVPGs in HF.

Beyond ejection fraction: an integrative approach for assessment of cardiac structure and function in heart failure.

Left ventricular ejection fraction (LVEF) has been the central parameter used for diagnosis and management in patients with heart failure. A good predictor of adverse outcomes in heart failure when below ∼45%, LVEF is less useful as a marker of risk as it approaches normal. As a measure of cardiac function, ejection fraction has several important limitations. Calculated as the stroke volume divided by end-diastolic volume, the estimation of ejection fraction is generally based on geometric assumptions that allow for assessment of volumes based on linear or two-dimensional measurements. Left ventricular ejection fraction is both preload- and afterload-dependent, can change substantially based on loading conditions, is only moderately reproducible, and represents only a single measure of risk in patients with heart failure. Moreover, the relationship between ejection fraction and risk in patients with heart failure is modified by factors such as hypertension, diabetes, and renal function. A more complete evaluation and understanding of left ventricular function in patients with heart failure requires a more comprehensive assessment: we conceptualize an integrative approach that incorporates measures of left and right ventricular function, left ventricular geometry, left atrial size, and valvular function, as well as non-imaging factors (such as clinical parameters and biomarkers), providing a comprehensive and accurate prediction of risk in heart failure.