Left Ventricular Blood Volume Research Articles

“Heart of the Matter”: Cardiac Dysfunction in Congenital Diaphragmatic Hernia

Despite advances in caring for neonates with congenital diaphragmatic hernia (CDH), mortality and morbidity continues to be high. Additionally, the pathophysiology of cardiac dysfunction in this condition is poorly understood. Postnatal cardiac dysfunction in neonates with CDH may be multifactorial with origins in fetal life. Mechanical obstruction, competition from herniated abdominal organs into thoracic cavity combined with redirection of ductus venosus flow away from patent foramen ovale leading to smaller left-sided structures may be a contributing factor. This shunting decreases left atrial and left ventricular blood volume, which may result in altered micro- and macrovascular aberrations affecting cardiac development in the prenatal period. Direct mass effect from herniated intra-abdominal contents restricting cardiac growth and/or reduced left ventricular preload may contribute independently to left ventricular dysfunction in the absence of right ventricular dysfunction and or pulmonary hypertension. With variable clinical phenotypes of cardiac dysfunction, pulmonary hypertension, and respiratory failure in patients with CDH, there is increased need for individualized diagnosis and tailored therapy. Routine use of therapy such as inhaled nitric oxide and sildenafil that induces significant pulmonary vasodilation may be detrimental in left ventricle dysfunction, whereas in a patient with pure right ventricle dysfunction, they may be beneficial. Targeted functional echocardiography serves as a real-time tool for defining the pathophysiology and aids optimization of vasoactive therapy in affected neonates. KEY POINTS: · Cardiac dysfunction in neonates with CDH is multifactorial.. · Postnatal cardiac dysfunction in patients with CDH has its origins in fetal life.. · Right ventricular dysfunction contributes to systemic hypotension.. · Left ventricular dysfunction contributes to systemic hypotension.. · Supportive therapy should be tailored to clinical phenotype..

Precision measurement of cardiac structure and function in cardiovascular magnetic resonance using machine learning

BackgroundMeasurement of cardiac structure and function from images (e.g. volumes, mass and derived parameters such as left ventricular (LV) ejection fraction [LVEF]) guides care for millions. This is best assessed using cardiovascular magnetic resonance (CMR), but image analysis is currently performed by individual clinicians, which introduces error. We sought to develop a machine learning algorithm for volumetric analysis of CMR images with demonstrably better precision than human analysis.MethodsA fully automated machine learning algorithm was trained on 1923 scans (10 scanner models, 13 institutions, 9 clinical conditions, 60,000 contours) and used to segment the LV blood volume and myocardium. Performance was quantified by measuring precision on an independent multi-site validation dataset with multiple pathologies with n = 109 patients, scanned twice. This dataset was augmented with a further 1277 patients scanned as part of routine clinical care to allow qualitative assessment of generalization ability by identifying mis-segmentations. Machine learning algorithm (‘machine’) performance was compared to three clinicians (‘human’) and a commercial tool (cvi42, Circle Cardiovascular Imaging).FindingsMachine analysis was quicker (20 s per patient) than human (13 min). Overall machine mis-segmentation rate was 1 in 479 images for the combined dataset, occurring mostly in rare pathologies not encountered in training. Without correcting these mis-segmentations, machine analysis had superior precision to three clinicians (e.g. scan-rescan coefficients of variation of human vs machine: LVEF 6.0% vs 4.2%, LV mass 4.8% vs. 3.6%; both P < 0.05), translating to a 46% reduction in required trial sample size using an LVEF endpoint.ConclusionWe present a fully automated algorithm for measuring LV structure and global systolic function that betters human performance for speed and precision.

Mapping electric bulk conductivity in the human heart.

To explore the technical feasibility of mapping the electric bulk conductivity in the human heart, and to determine quantitative conductivity values of myocardium and blood from a small group of volunteers. Using a 3T MR system, 6 healthy male volunteers were measured. For all volunteers, a time-resolved 2D sequence over the cardiac cycle was applied (electrocardiogram [ECG]-triggered SSFP acquired in breath-hold). From these data, a dedicated, so-called "2D conductivity" has been derived in the framework of electrical properties tomography (EPT). To validate the concept of 2D conductivity, a static 3D sequence (ECG-triggered and respiratory-gated SSFP 3D whole heart acquisition, allowing the full 3D reconstruction of conductivity) as well as a Q-flow sequence (for investigating the relation between flow and reconstruction errors of the conductivity) have been applied for one of the volunteers. For both, blood and myocardium, quantitative values of obtained 2D conductivity were approximately two-thirds of the obtained 3D conductivity, as expected from Maxwell's equations. Furthermore, the quantitative conductivity values agreed with corresponding literature values. Conductivity of left-ventricular blood volume showed characteristic over- and under-shooting at specific time points during the cardiac cycle for all volunteers investigated. This over- and under-shooting correlated with the phase pattern caused by blood flow into/out of the ventricle. The study demonstrated the technical feasibility of cardiac conductivity measurements using standard MR systems and standard MR sequences, and therefore, may open new options for MR-based cardiac diagnosis.

Improved Efficiency of Intraventricular Blood Flow Transit Under Cardiac Stress: A 4D Flow Dobutamine CMR Study.

Introduction: The effects of heart rate, inotropy, and lusitropy on multidimensional flow patterns and energetics within the human heart remain undefined. Recently, reduced volume and end-diastolic kinetic energy (KE) of the portion of left ventricular (LV) inflow passing directly to outflow, Direct flow (DF), have been shown to reflect inefficient LV pumping and to be a marker of LV dysfunction in heart failure patients. In this study, we hypothesized that increasing heart rate, inotropy, and lusitropy would result in an increased efficiency of intraventricular blood flow transit. Therefore, we sought to investigate LV 4D blood flow patterns and energetics with dobutamine infusion.Methods: 4D flow and morphological cardiovascular magnetic resonance (CMR) data were acquired in twelve healthy subjects: at rest and with dobutamine infusion to achieve a target heart rate ~60% higher than the resting heart rate. A previously validated method was used for flow analysis: pathlines were emitted from the end-diastolic (ED) LV blood volume and traced forward and backward in time to separate four functional LV flow components. For each flow component, KE/mL blood volume at ED was calculated.Results: With dobutamine infusion there was an increase in heart rate (64%, p < 0.001), systolic blood pressure (p = 0.02) and stroke volume (p = 0.01). Of the 4D flow parameters, the most efficient flow component (DF), increased its proportion of EDV (p < 0.001). The EDV proportion of Residual volume, the blood residing in the ventricle over at least two cardiac cycles, decreased (p < 0.001). The KE/mL at ED for all flow components increased (p < 0.001). DF had the largest absolute and relative increase while Residual volume had the smallest absolute and relative increase.Conclusions: This study demonstrates that it is feasible to compare 4D flow patterns within the normal human heart at rest and with stress. At higher heart rate, inotropy and lusitropy, elicited by dobutamine infusion, the efficiency of intraventricular blood flow transit improves, as quantified by an increased relative volume and pre-systolic KE of the most efficient DF component of the LV volume. The change in these markers may allow a novel assessment of LV function and LV dysfunction over a range of stress.

Left ventricular blood flow patterns at rest and under dobutamine stress in healthy pigs.

Intracardiac blood flow patterns are affected by the morphology of cardiac structures and are set up to support the heart's pump function. Exercise affects contractility and chamber size as well as pre- and afterload. The aim of this study was to test the feasibility of four-dimensional phase contrast cardiovascular MRI under pharmacological stress and to study left ventricular blood flow under stress. 4D flow data were successfully acquired and analysed in 12 animals. During dobutamine infusion, heart rate and ejection fraction increased (82±5bpm versus 124±3bpm/46±9% versus 65±7%; both p<0.05). A decrease in left ventricular end-diastolic volume (72±14mL versus 55±8mL; p<0.05) and end-systolic volume (40±15mL versus 19±6mL; p<0.05) but no change in stroke volume were observed. Trans-mitral diastolic inflow velocity increased under dobutamine and the trajectory of inflowing blood was directed towards the anterior septum with increased inflow angle (26±5°) when compared with controls (15±2°). In 5/6 animals undergoing stress diastolic vortices developed later, and in 3/6 animals vortices collapsed earlier with significantly smaller cross-sectional area during diastole. The vorticity index was not affected. Under the stress condition direct flow (% ejection within the next heart beat) increased from 43±6% to 53±8%. 4D MRI blood flow acquisition and analysis are feasible in pig hearts under dobutamine-induced stress. Flow patterns characterized by high blood velocity and antero-septally oriented diastolic inflow as well as decreased ventricular volumes are unfavourable conditions for diastolic vortex development under pharmacological stress, and cardiac output is increased by a rise in heart rate and directly ejected left ventricular blood volume.

Relationship between Stroke Volume and Pulse Pressure during Blood Volume Perturbation: A Mathematical Analysis

Arterial pulse pressure has been widely used as surrogate of stroke volume, for example, in the guidance of fluid therapy. However, recent experimental investigations suggest that arterial pulse pressure is not linearly proportional to stroke volume. However, mechanisms underlying the relation between the two have not been clearly understood. The goal of this study was to elucidate how arterial pulse pressure and stroke volume respond to a perturbation in the left ventricular blood volume based on a systematic mathematical analysis. Both our mathematical analysis and experimental data showed that the relative change in arterial pulse pressure due to a left ventricular blood volume perturbation was consistently smaller than the corresponding relative change in stroke volume, due to the nonlinear left ventricular pressure-volume relation during diastole that reduces the sensitivity of arterial pulse pressure to perturbations in the left ventricular blood volume. Therefore, arterial pulse pressure must be used with care when used as surrogate of stroke volume in guiding fluid therapy.

Aortic valve timing is critical for accurate estimation of MRI-derived ejection fraction

Background We aim to investigate the effect of utilizing aortic valve timing in the measurement of cardiac magnetic resonance (CMR)-derived ejection fraction (EF). Although CMR-derived left ventricular (LV) EF is the gold-standard for volumetric evaluation of the heart, it always reports higher values when compared to other modalities such as echocardiography and radionuclide ventriculography. The higher EF has often been attributed to better endocardial definition by CMR. In the ACCF/ACR/ AHA/NASCI/SCMR 2010 Expert Consensus Document on CMR, a 1987 paper is cited with utilizes the “maximal and minimal left ventricular cross-sectional area at the mid-ventricle” to identify end-systole and end-diastole. The 2013 CMR Guideline suggests phases with the largest and smallest global LV blood volume be utilized to identify end-diastole and end-systole. The same guideline also suggests aortic valve timing be utilized when arrhythmia or mitral regurgitation is encountered. We investigated the effect of different schemes on measured LVEF. Methods Standard retrospectively EKG-gated bSSFP short axis and LVOT cine images in 46 clinical patients in normal sinus rhythm with a range of EF (5.8 75.8 %) were acquired and analyzed. Scan parameters were as follows: in-plane resolution: 1.25 2.08 mm, slice spacing: 8 mm with a gap of 2 mm, reconstructed temporal resolution: 18.2 58.8 ms. Aortic valve opening and closing as a percentage of cardiac cycle was identified on LVOT images. Volumetric evaluation of short axis images was performed via semi-automated segmentation for all phases and all left ventricular slices (ITK-SNAP, Philadelphia PA). The schemes (shown in Table 1) were used to quantify LVEF. Scheme G was considered “true EF” and usied aortic valve opening and closing. Scheme F is intended to mimic real-time methods, which acquire slice-by-slice data and do not incorporate aortic valve timing or other external measures such as EKG.

Left ventricular epicardial admittance measurement for detection of acute LV dilation

There are two implanted heart failure warning systems incorporated into biventricular pacemakers/automatic implantable cardiac defibrillators and tested in clinical trials: right heart pressures, and lung conductance measurements. However, both warning systems postdate measures of the earliest indicator of impending heart failure: left ventricular (LV) volume. There are currently no proposed implanted technologies that can perform LV blood volume measurements in humans. We propose to solve this problem by incorporating an admittance measurement system onto currently deployed biventricular and automatic implantable cardiac defibrillator leads. This study will demonstrate that an admittance measurement system can detect LV blood conductance from the epicardial position, despite the current generating and sensing electrodes being in constant motion with the heart, and with dynamic removal of the myocardial component of the returning voltage signal. Specifically, in 11 pigs, it will be demonstrated that 1) a physiological LV blood conductance signal can be derived; 2) LV dilation in response to dose-response intravenous neosynephrine can be detected by blood conductance in a similar fashion to the standard of endocardial crystals when admittance is used, but not when only traditional conductance is used; 3) the physiological impact of acute left anterior descending coronary artery occlusion and resultant LV dilation can be detected by blood conductance, before the anticipated secondary rise in right ventricular systolic pressure; and 4) a pleural effusion simulated by placing saline outside the pericardium does not serve as a source of artifact for blood conductance measurements.

Obesity, obstructive sleep apnoea, and diabetes mellitus: anaesthetic implications

Obesity is an epidemic in much of the Western World. The extent of this problem, combined with the increasing preference for ambulatory surgical procedures, has produced a difficult situation for many anaesthesiologists. Even the simplest anaesthetic procedures can become very complicated and potentially difficult in this population. Although there are numerous complications associated with obesity, perhaps obstructive sleep apnoea (OSA) and diabetes mellitus are among the more significant. Patients with OSA are often not ideal candidates for certain day-case procedures, but many outpatient procedures can be performed on patients with OSA as long as attention is paid to anaesthetic technique. Diabetic patients are prone to numerous complications in the perioperative period, including cardiac problems, but with careful management, they are able to undergo day-case surgical procedures safely.

Impact of physiological variables and genetic background on myocardial frequency-resistivity relations in the intact beating murine heart

Conductance measurements for generation of an instantaneous left ventricular (LV) volume signal in the mouse are limited, because the volume signal is a combination of blood and LV muscle, and only the blood signal is desired. We have developed a conductance system that operates at two simultaneous frequencies to identify and remove the myocardial contribution to the instantaneous volume signal. This system is based on the observation that myocardial resistivity varies with frequency, whereas blood resistivity does not. For calculation of LV blood volume with the dual-frequency conductance system in mice, in vivo murine myocardial resistivity was measured and combined with an analytic approach. The goals of the present study were to identify and minimize the sources of error in the measurement of myocardial resistivity to enhance the accuracy of the dual-frequency conductance system. We extended these findings to a gene-altered mouse model to determine the impact of measured myocardial resistivity on the calculation of LV pressure-volume relations. We examined the impact of temperature, timing of the measurement during the cardiac cycle, breeding strain, anisotropy, and intrameasurement and interanimal variability on the measurement of intact murine myocardial resistivity. Applying this knowledge to diabetic and nondiabetic 11- and 20- to 24-wk-old mice, we demonstrated differences in myocardial resistivity at low frequencies, enhancement of LV systolic function at 11 wk and LV dilation at 20-24 wk, and histological and electron-microscopic studies demonstrating greater glycogen deposition in the diabetic mice. This study demonstrated the accurate technique of measuring myocardial resistivity and its impact on the determination of LV pressure-volume relations in gene-altered mice.

Perioperative considerations in the patient with a left ventricular assist device.

Perioperative considerations in the patient with a left ventricular assist device.

Influence of Surrounding Structures on Parallel Volume Determinations by Conductance Catheter

When left ventricular blood volume is evaluated by the conductance catheter technique, an important fraction of the injected current “leaks” into the surrounding tissues giving rise to a parallel volume (Vp). To study the influence of the thoracic structures on Vp, 5 anesthetized dogs were studied during (a) closed thorax, (b) open thorax, (c) reclosed thorax without pericardium, (d) open thorax without pericardium, (e) replacing the pericardium with a nonconducting bag. Intraventricular volume and pressure, surface ECG, and Vp (determined by saline dilution technique) were monitored during each condition. A conductance diagram was used to represent the behavior of the structures within the thoracic cage, including cardiac muscle, pericardium, and also other structures (OS) such as lung, skeletal muscle, and bone tissues. Under conditions (a) and (b), Vp was not significantly different (p < 0.005); thus, changes in OS did not much modify Vp. When the pericardium was removed, the average Vp values for conditions (c) and (d) were smaller than those for (a) and (b) (p < 0.005). Apparently, because of good conductivity, the pericardium would favor the passage of current. Finally, when the fifth condition (e) was compared with (a) or (b), the differences were highly significant (p < 0.005), while the differences between (e) and either (c) or (d) were less significant and more variable (p < 0.05). Duncan's multiple comparisons by pairs confirmed the previous statements. The relative fraction of the total measured volume through the surrounding tissues (p%) systematically decreased as we moved from condition (a) to (e). Condition (e) decidedly forced a concentration of current lines through the myocardium. In conclusion, the pericardium is responsible for a significant fraction of the loss, which should be separated out from that due to the myocardium and OS. The latter would contribute to Vp with not more than about 10%

Hearts, neck posture and metabolic intensity of sauropod dinosaurs.

Hypothesized upright neck postures in sauropod dinosaurs require systemic arterial blood pressures reaching 700 mmHg at the heart. Recent data on ventricular wall stress indicate that their left ventricles would have weighed 15 times those of similarly sized whales. Such dimensionally, energetically and mechanically disadvantageous ventricles were highly unlikely in an endothermic sauropod. Accessory hearts or a siphon mechanism, with sub-atmospheric blood pressures in the head, were also not feasible. If the blood flow requirements of sauropods were typical of ectotherms, the left-ventricular blood volume and mass would have been smaller; nevertheless, the heart would have suffered the serious mechanical disadvantage of thick walls. It is doubtful that any large sauropod could have raised its neck vertically and endured high arterial blood pressure, and it certainly could not if it had high metabolic rates characteristic of endotherms.

Development of a multifrequency conductance catheter-based system to determine LV function in mice.

Transgenic mice offer a valuable way to relate gene products to phenotype, but the ability to assess the cardiovascular phenotype with pressure-volume analysis has lagged. Conductance measurement offers a method to generate an instantaneous left ventricular (LV) volume signal in the mouse but has been limited by the volume signal being a combination of blood and LV muscle. We hypothesized that by developing a mouse conductance system that operates at several simultaneous frequencies, we could identify and correct for the myocardial contribution to the instantaneous volume signal. This hypothesis is based on the assumption that mouse myocardial conductivity will vary with frequency, whereas mouse blood conductivity will not. Consistent with this hypothesis, we demonstrated that at higher excitation frequency, greater end-diastolic and end-systolic conductance are detected, as well as a smaller difference between the two. We then empirically solved for LV blood volume using two frequencies. We combined measured resistivity of mouse myocardium with an analytic approach and extracted an estimate of LV blood volume from the raw conductance signal. Development of a multifrequency catheter-based system to determine LV function could be a tool to assess cardiovascular phenotype in transgenic mice.

Impedance Catheter Volume Estimation

Innovative cardiac performance evaluation methods require simultaneous absolute pressure and volume. Impedance catheter volumetry determines volume by measuring intracavitary potentials generated along the catheter by an impressed current in the left ventricular blood volume, but the conventional method can exhibit unacceptable absolute errors (>50%). Deterministic estimators were developed from field theory to determine geometry and myocardial conductivity from potential measurements alone. These worked in noise-free, spherical and spheroidal models but failed with measurement noise. Utilizing statistical training data allowed incorporating a priori information concerning the relationship between potentials and volume in a given ventricle. This procedure resulted in volume estimates that were not highly sensitive to noise. Both in model simulations and animal testing, error reductions of over 50% were observed, yielding absolute volumes accurate to 15–20%.

Direct percutaneous heart puncture.

1. The procedure of direct percutaneous left heart puncture is mentioned. 2. Cases of mitral valvular disease are classified by a circulatory dynamical analysis of the superimposed pattern of left atrial and left ventricular pressure curves. 3. Cases of aortic valvular disease are classified by a circulatory dynamical analysis of the superimposed pattern of left ventricular and ascending aortic pressure curves. 4. True lung blood volume, left atrial blood volume and left ventricular blood volume are calculated by an original method.