Total Systemic Flow Research Articles

Extended period of ventilation before delayed cord clamping augments left-to-right shunting and decreases systemic perfusion at birth in preterm lambs.

Previous studies have suggested that an extended period of ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. However, it is unknown whether this greater rise in PA flow is accompanied by increases in left ventricular (LV) output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale (FO), with decreased systemic arterial perfusion. Using an established preterm lamb birth transition model, this study compared the effect of a short (∼40s, n=11), moderate (∼2min, n=11) or extended (∼5min, n=12) period of initial mechanical lung ventilation before DCC on flow probe-derived perinatal changes in PA flow, LV output, total systemic arterial blood flow, ductal shunting and FO shunting. The LV output was relatively stable during initial ventilation but increased after DCC, with similar responses in all groups. Systemic arterial flow patterns displayed only minor differences during brief and moderate periods of initial ventilation and were similar after DCC. However, an increase in PA flow was augmented with an extended initial ventilation (P < 0.001), owing to an earlier onset of left-to-right ductal and FO shunting (P < 0.001), and was accompanied by a pronounced reduction in total systemic arterial flow (P=0.005) that persisted for 4min after DCC (P ≤ 0.039). These findings suggest that, owing to increased left-to-right shunting and a greater reduction in systemic arterial perfusion, an extended period of ventilation before DCC does not result in greater perinatal circulatory benefits than shorter periods of initial ventilation in the birth transition. KEY POINTS: Previous studies suggest that an extended period of initial ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. It is unknown whether this greater rise in PA flow is accompanied by an increased left ventricular output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale, with decreased systemic arterial perfusion. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent a brief (∼40s), moderate (∼2min) or extended (∼5min) period of ventilation before DCC. Perinatal changes in left ventricular output were similar in all groups, but extended initial ventilation augmented both perinatal increases in PA flow, owing to earlier onset and greater left-to-right ductal and foramen ovale shunting, and perinatal reductions in total systemic arterial perfusion. Extended ventilation before DCC does not confer a greater perinatal circulatory benefit than shorter periods of initial ventilation.

The impact of ECPELLA on haemodynamics and global oxygen delivery: a comprehensive simulation of biventricular failure

BackgroundECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO2) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO2 into our developed cardiovascular simulation.Methods and resultsBoth the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure–volume relationship (PV loop), and global DO2 under different VA-ECMO flows and Impella support levels.ResultsIn the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure–volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV–PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO2 increment under ECPELLA total support conditions.ConclusionsThe optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO2 in total ECPELLA support conditions.

The effect of intra-aortic balloon pumping on hemodynamics and left ventricular load in Impella-supported condition: A simulation study

Abstract Introduction Intra-aortic balloon pumping (IABP) is a commonly used percutaneous mechanical circulatory support device. Although IABP combined with Impella, a percutaneous left ventricular assist device, has shown positive outcomes in a few case reports of acute heart failure, its hemodynamic and left ventricular (LV) unloading effects remain unclear. Purpose We conducted a simulation study to clarify the clinical benefits of adding IABP to Impella-supported conditions. Methods We used SimulinkⓇ for cardiovascular simulation. The systemic and pulmonary circulation were modelled by using a 5-element resistance-capacitance network with four ventricles represented by time-varying elastance and unidirectional valves (Figure 1A). We compared total systemic flow, coronary perfusion pressure (CPP), and pressure-volume relationships (PV loop) in severe LV dysfunction (LV end-systolic elastance: 0.2 mmHg/mL) under three scenarios: IABP with a 40 mL balloon volume added to baseline, IABP added to Impella CP support at P2 (partial support) and P8 (total support) (Figure 1B). Results As shown in Figure 2A, IABP increased total systemic flow and CPP, and shifted the PV loop to the left. In P2-Impella condition, the addition of IABP increased native cardiac output (0.3 to 0.7 L/min) and total systemic flow (2.7 to 2.9 L/min), while decreased Impella pump flow due to increased afterload of Impella during diastole. IABP further moved PV loop leftward and reduced LV pressure-volume area (PVA) by -3.8% from Impella only and -7.8% from baseline (Figure 2B). In P8-Impella condition, IABP did not change total systemic flow, CPP, or PV loop (Figure 2C). Conclusions The addition of IABP to Impella could increase CPP while increasing Impella pump afterload and decreasing Impella flow. Overall, IABP slightly increased total systemic flow and decreased LV workload in Impella partial support condition. In specific clinical situations, IABP has the potential to be used as adjuvant therapy alongside Impella partial support.Figure 1

The Functioning of the Frog’s Single Ventricle

African clawed frog (Xenopus laevis) has double-inlet and single-outlet single ventricle supporting both systemic and pulmonary circulations, with normal lifespan of 25-30 years. The relationship between pulmonary and systemic blood flows was investigated using echocardiography. Twelve female African clawed frogs, age 18-24 months, mean weight 173±19 grams were studied. Heart rate, percutaneous oxygen saturation, echocardiography derived 2D and blood flow in all cardiovascular structures were measured in two temperature setting, 17◦C (normal environment for frogs) and 22 C. In eight frogs cerebral Near-Infra-Red Spectroscopy (NIRS) was measured. Mean oxygen saturation was 66±9% with temperature of 22◦C and 85±6% with 17◦C (P&lt;0.001), while there was no statistical difference between mean heart rates, respectively 48 13 and 42±7 beats/min. Doppler echocardiography showed a mean total pulmonary blood flow (QP) =173.0 ml/min and mean total systemic blood flow (QS) = 99.3ml/min, with mean QP/QS of 1.74:1.00. The only statistical correlation between size of the cardiovascular structures and body weight was found for the pulmonary veins, with correlation coefficient = 0.71 (P=0.02). NIRS measurements showed a reverse correlation (coefficient = -0.21) with oxygen saturation. The frog’s heart has peculiar morphologic and functional characteristics allowing normal quality of life for many years despite the presence of single ventricle. Baseline QP/QS under general anesthesia was significant for increased total pulmonary blood flow. Exposure to environmental temperature 5◦C higher than normal caused peripheral vasodilatation, with subsequent decrease of QP/QS and reduced oxygenation.

The impact of aortic valve regurgitation on the combination therapy of VA-ECMO and Imeplla support in severe cardiogenic shock: a simulation study

Background: The utilization of a combination of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, ECPELLA, has become widespread among patients with cardiogenic shock. The utilization of VA-ECMO in the presence of aortic regurgitation (AR) can result in significant left ventricular (LV) distention. Additionally, the implantation of Impella via the aortic valve frequently induces AR clinically. We established a simulation model and evaluated the impact of AR on hemodynamics under ECPELLA. Furthermore, assuming that the reverse flow of AR is strongly determined by aortic pressure (AP) level, we simulated a scenario where AP was further decreased. Methods: We employed Simulink® (Mathworks, Inc.). The systemic and pulmonary circulations were modeled using a 5-element resistance-capacitance network. Four cardiac chambers were represented by time-varying elastance. We compared the aortic regurgitant flow (Far), total systemic flow (Ftotal), and LV pressure-volume relationship under various severities of AR and varying Impella (0-3.7 L/min) and VA-ECMO (0-5 L/min) flows. AR grades were adjusted by the regurgitant resistance and classified as mild, moderate, and severe, mimicking a clinical scenario. Results: Without AR, ECMO significantly increased Ftotal and raised LV end-diastolic pressure (LVEDP). Impella increased Ftotal and decreased LVEDP. The concomitant presence of AR exacerbated the increase of LVEDP by ECMO and the reduction of LVEDP by Impella. Under ECPELLA support (VA-ECMO: 3 L/min) with mild AR, the increase of Impella support (1 to 3.5 L) increased Ftotal and Far, while decreasing LVEDP, indicating the prevention of AR-induced LV distention. Additionally, the presence of mild AR prevented the Impella-induced left ventricular suction that is commonly observed under ECPELLA support with high-flow VA-ECMO. In the case of moderate AR, while the hemodynamic trends were similar to those observed under mild AR, Impella was unable to prevent the increment of LVEDP to a critical level (&lt; 20 mmHg). However, by decreasing AP through reducing resistance (e.g. vasodilators), both Far and LVEDP were dramatically reduced and Ftotal was increased under ECPELLA support. Conclusion: The concomitant presence of AR in ECPELLA condition increased LV load, while prevented LV suction. The use of vasodilator in ECPELLA with AR could attenuate AR, increase systemic perfusion, and reduce LV load. The optimal control of Impella and VA-ECMO flows and AP can maximize the hemodynamic and LV unloading impacts of ECPELLA. no funding This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Mathematical Model of Artificial Pulse Synchronization for the HeartMate3 Left Ventricular Assist Device.

Constant speed control of rotary LVADs attenuates vascular pulsatility, which has been linked to clinical complications such as thrombus formation, bleeding, and valvular dysfunction. Speed modulation can improve pulsatility and washout, but optimization requires coordination with the native heartbeat. A simple mathematical model of the left ventricle-left ventricular assist device (LV-LVAD) flow interaction was developed that sums the individual contributions of the native LV and the HeartMate3 artificial pulse (AP) to predict the total systemic flow. The model flow and pulsatility predictions results were in good agreement with experimental data from a mock circulatory loop measured for full bypass support conditions. The model was used to evaluate three schemes for optimizing the synchronization of the AP with the native heart. The optimized interaction occurred when the AP speed increase occurred during contraction, resulting in a doubling of flow pulsatility, and corresponded to an increase in the area enclosed by the dynamic pressure-flow relation. The model provides a simple tool for exploring the optimization of LVAD speed modulation that can reduce the time and expense of mock loop studies during the development process.

Benefits and Risks of Delayed Surgery for Ventricular Septal Rupture after Acute Myocardial Infarction.

The timing of surgery for ventricular septal rupture (VSR) after acute myocardial infarction (AMI) remains controversial. This study investigated the benefits and risks of delayed surgery for post-AMI VSR and examined differences in echocardiographic findings between early and delay groups.A total of 38 consecutive patients with post-AMI VSR who underwent surgery at our hospital between May 2003 and November 2020 were retrospectively analyzed. Our strategy was to delay surgery until 2 weeks after AMI. If patients demonstrated organ dysfunction, we considered early surgery. Patients were divided into early (n = 20; 53%) and delay (n = 18; 47%) groups. Risks and benefits were investigated based on echocardiographic findings during the waiting period. The delay group had more preoperative intravenous catheter infections (P = 0.008) but fewer reoperations (P = 0.02) and lower operative mortality (P = 0.04) than the early group. The VSR defect diameter and total pulmonary blood flow to total systemic blood flow (Qp/Qs) increased in both groups while waiting. Nevertheless, the early group had a significantly higher Qp/Qs change rate than the delay group (P = 0.05). The 30 day and hospital mortality rates were 5.3% and 13.2%, respectively.The VSR defect diameter and Qp/Qs in both groups increased with time and can therefore become risk factors. Nonetheless, the benefit of waiting exceeded the risk because our outcomes were better than those previously reported.

MRI Phase-Contrast Blood Flow in Fasting Pediatric Patients with Fontan Circulation Correlates with Exercise Capacity.

To assess regional blood flow in fasting pediatric patients with Fontan circulation by using MRI and to explore associations with clinical parameters. In this retrospective study, pediatric patients who had undergone the Fontan procedure (<18 years of age) and had undergone clinical cardiac MRI, performed after at least 4 hours of fasting, between 2018 and 2021 were included. Regional blood flow was compared with published healthy volunteer data (n = 19) and assessed in relation to hemodynamic parameters and clinical status. Data are presented as medians, with first to third quartiles in parentheses. Mann-Whitney U, Kruskal-Wallis, χ2, and Spearman rank correlation tests were used. Fifty-five patients (38 boys) with median age at MRI of 14 years (IQR, 11-16 years) and median time from Fontan procedure to MRI of 10 years (IQR, 8-12 years) were included. Patients after Fontan procedure had lower ascending aortic, inferior vena cava, and total systemic blood flow compared with healthy volunteers (3.00 L/min/m2 [IQR, 2.75-3.30 L/min/m2] vs 3.61 L/min/m2 [IQR, 3.29-4.07 L/min/m2]; 1.73 L/min/m2 [IQR, 1.40-1.94 L/min/m2] vs 2.24 L/min/m2 [IQR, 2.06-2.75 L/min/m2]; 2.78 L/min/m2 [IQR, 2.45-3.10 L/min/m2] vs 3.95 L/min/m2 [IQR, 3.20-4.30 L/min/m2], respectively; P < .001). Portal vein flow was greater than hepatic vein flow in 25% of patients. Fontan blood flow was inversely correlated with pre-Fontan mean pulmonary artery pressure (Spearman rank correlation coefficient [rs ]= -0.42, P = .005) and ventricular end diastolic pressure (rs = -0.33, P = .04) and positively correlated with post-Fontan percent predicted oxygen consumption at peak workload (rs = 0.34, P = .02). Reference ranges are provided for regional systemic blood flow derived by using MRI in fasting pediatric patients with Fontan circulation, who had lower systemic blood flow compared with healthy volunteers. Lower fasting Fontan blood flow correlated with lower exercise capacity.Keywords: Pediatrics, Heart, Congenital, MR Imaging, Hemodynamics/Flow Dynamics, Cardiac Supplemental material is available for this article. © RSNA, 2022.

Impact of Left Ventricular Unloading Under Circulatory Support with Venoarterial ECMO in Heart Failure Animal Model

<h3>Purpose</h3> An additional left ventricular (LV) unloading device could be effective for LV distension caused by V-A ECMO. However, the appropriate flow proportion between V-A ECMO and LV unloading devices has still been controversial. The purpose of this study was to evaluate the effect of flow proportion between V-A ECMO and LV unloading. <h3>Methods</h3> Microsphere was injected to the left anterior descending artery of 12 adult sheep to induce myocardial ischemia, aiming at the criteria of cardiac output to be less than 50% of that before the microsphere injection. V-A ECMO was established between the right atrium and the abdominal aorta. LV unloading was performed by venting blood from LV apex to the abdominal aorta using a centrifugal pump. V-A ECMO support and LV unloading were maintained for 6 hours with a total systemic flow to be 80-100ml/kg/min. We categorized into 3 groups based on different mechanical circulatory configurations and flow proportion: No LV unloading group (V-A ECMO without LV unloading), Low LV unloading group (LV unloading with V-A ECMO, ECMO: LV venting=3:1), and High LV unloading group (LV unloading with V-A ECMO, ECMO: LV venting=1:1). The LV and right ventricle (RV) functions of these 3 groups were investigated by analyzing hemodynamic parameters as well as the evaluation of LV pressure-volume loops and echocardiography. <h3>Results</h3> During the V-A ECMO support, LVEDP and potential energy of Low and High LV unloading groups were significantly lower than that of No LV unloading group (Figure1A). The RVDd/ LVDd ratio on echocardiography of High LV unloading group was higher than that of Low LV unloading group, while RVFAC of High LV unloading group was lower than that of Low LV unloading group (Figure 1B), suggesting that high LV unloading could be related to RV dysfunction. <h3>Conclusion</h3> LV unloading is mandatory for V-A ECMO in avoiding LV dysfunction, whereas excessive LV unloading has the possibility to cause RV dysfunction.

Dynamic pressure-flow curve analysis of the native heart and left ventricular assist device for full and partial bypass conditions.

During left ventricular assist device (LVAD) support, the external work performed by the native heart combines with the work performed by the rotary LVAD to provide cyclic flow through the LVAD and, in some conditions, through the aortic valve. In this study, a balance of external work was developed and validated for both full and partial bypass conditions that includes valve opening and aortic compliance. The theory assumes a steady-state contribution of external work from the rotary LVAD and a dynamic portion from the heart. Cyclic flow may be ejected through either the LVAD or ascending aorta, and an energy absorption term accounts for aortic compliance. Mock loop studies were performed for LV ejection fractions of 10%-28% combined with HeartMate II LVAD support at 8 and 11krpm to produce a range of full and partial bypass conditions. The external work of the LVAD and native heart was computed from the experimental pressure-flow (H-Q) relations and compared to the theory. Native heart contraction produces a counterclockwise loop in the pressure-flow relation of the LVAD which increased with ejection fraction, and during full bypass conditions the external work was preserved in the total systemic flow. During partial bypass conditions, forward flow through the ascending aorta was accompanied by a reversal during aortic valve closure resulting in a reduction in energy in the downstream flow. The study presents a balance of external work during full and partial bypass LVAD support. Experimental data validated the additional terms corresponding to forward flow and aortic compliance that contribute to the system balance. This expanded theory can be applied to LVAD design and control to improve pulsatility and aortic valve biomechanics.

Mechanical Circulatory Support for Biventricular Heart Failure Using Advanced Ventricular Assist Device

In patients with severe biventricular heart failure (HF) and cardiogenic shock, use of biventricular assist device (BVAD) can be a treatment of choice. We are developing an advanced ventricular assist device (AVAD) intended to serve as universal pump for left and/or right heart failure (Fig.1 A,B). The purpose of this initial in silico simulation study was to demonstrate that AVAD design can be suitable for biventricular support. The virtual mock loop (VML) was developed (MATLAB; MathWorks®) to simulate hemodynamic parameters as they surge through the BVAD-supported systolic HF cardiovascular system. The AVAD used as in BVAD configuration was in 2 speeds (3400 rpm left, 2000 rpm right) to get comparable systemic flow and pressure outputs. LVAD support was adjusted to maintain 5.0 L/min total systemic flow. For BVAD, the added RVAD support was adjusted to maintain left and right atrial pressure (LAP-RAP) at 3-5 mm Hg. The BVAD performance was maintained very well for both left ventricular (L-AVAD) and right ventricular (R-AVAD) support within specified speed range (Fig1 C,D). L- AVAD speed of 3000 - 3500 rpm provided sufficient support for the case of severe left and right systolic heart failure, assuming there was no aortic valve regurgitation. At the simulated condition, with L-AVAD support, the aortic valve remains closed and the systemic pressure has reduced pulse. A stable hemodynamics were maintained. The atrial pressure difference (LAP-RAP) resulted to be sensitive to the right pump speed, though was balanced whenever there was any positive flow through the pulmonary valve. Introduction of R-AVAD support to the L-AVAD support caused the left atrial pressure to increase resulting in increased filling of the left ventricle and a corresponding increase in aortic pulsatility. These initial in silico study demonstrated that use of the universal AVAD as BVAD supports cardiac output and arterial pressure in biventricular HF condition.

Study on in vitro performance verification protocol for left ventricular assist device.

In vitro performance verification of ventricular assist devices using a mock circulatory loop is a prominent step to guarantee the system responses and the device performance and safety before the in vivo tests and ultimately clinical trials. In this article, we performed a comprehensive literature research to establish a verification matrix consisting of 12 test cases, defined by a set of physiological parameters which are commonly used to characterize a physiological condition. The clinical hemodynamic indicators for defining successful mechanical support were used as the acceptance criteria. A mock circulatory loop was customized to simulate the test cases, and a full verification protocol was described in details. An example left ventricular assist device was incorporated in the loop to accomplish a standard ventricular assist device performance verification. The test cases based on clinical data with sufficient safety margin represent our understanding in defining the extremes of operation. The mock circulatory loop was capable of generating the test conditions in the verification matrix and reproducing the Frank-Starling law of the native heart. The effect of the left ventricular assist device assistance (characterized by the total systemic flow, mean aortic pressure, and left atrial pressure) was well verified by the proposed protocol and acceptance criteria. To date, all left ventricular assist devices made in China have been evaluated according this protocol and some of them have entered the clinical trial stage. We are closely observing the clinical data in order to further improve the performance of the platform and encourage more advances in mechanical circulatory assist devices.

Current Role of the Total Artificial Heart in the Management of Advanced Heart Failure.

The total artificial heart (TAH) is a form of mechanical circulatory support that involves resection of the native ventricles followed by placement of a device that can restore total pulmonary and systemic flow. Given the increasing burden of congestive heart failure and cardiovascular disease, the number of people in need of cardiac replacement therapy will continue to grow. Despite aggressive efforts to expand the donor pool, the number of heart transplants in the United States (US) has plateaued at less than 3000 per year. In addition, there is increasing recognition of the long-term complications of current generation left ventricular assist devices such as progressive aortic insufficiency, complications related to blood trauma, and both early and delayed right ventricular failure. These factors may serve to expand the role of the TAH in the treatment of patients with end-stage heart failure particularly if new generation devices are developed that are durable, have an improved safety profile, and are totally implantable. PURPOSE OF REVIEW: To review the role and current evidence of the use of the TAH in the management of advanced heart failure and discuss development of recent TAHs that may have an impact on the field in the near future. RECENT FINDINGS: Many patients that receive a heart transplant are bridged with a mechanical support device, most commonly a left ventricular assist device (LVAD). However, there is a small subset of patients with profound biventricular (BV) failure or structural abnormalities that preclude LVAD placement, who will require support with a biventricular assist device (BiVAD) or TAH. There are numerous studies showing the efficacy of the TAH in bridging to transplantation. Also, recent studies have shown equal rates of bridging to transplantation between patients receiving a TAH compared to a BiVAD. However, BiVAD support has a higher incidence of stroke in addition to complications related to the native heart such as arrhythmias and valve dysfunction. Currently, there are multiple new generation artificial hearts in both preclinical development and in clinical trials for both bridge to transplant and destination therapy. TAH have been shown to be effective for circulatory support in select patients with end-stage heart failure. Current LVADs are associated with significant long-term complications related to retention of the native heart and pump design. Many of these complications may be addressed by the increased use of cardiac replacement therapy, i.e., total artificial hearts. Multiple generations of both pulsatile and advanced design continuous flow TAH are under development which have the potential to expand the role of TAHs.

The effect of distal pulmonary obstruction or elevated atrial pressures on pulmonary flow and pulmonary vascular disease: a mathematical flow circuit analogy model-based analysis.

Late presentation of large left to right shunts is a major problem in developing countries and evaluating the operability is a challenge during preoperative evaluation. The factors that determine the development and progression of the pulmonary vascular disease are still largely unknown, though there is evidence to show that increased pulmonary flow is the main contributing factor. We have found cases of operability despite late presentation of ventricular septal defect (VSD). In some of these cases, the reason for operability may lie in associations. We herein attempt to provide a mathematical explanation for their operability. To assess the effect of different levels of obstruction and elevated ventricular end-diastolic pressure on pulmonary flow. Mathematical flow analogy models were constructed and analysed based on Ohm's law and the laws governing flow in series and parallel flow circuits. Any narrowing in the pulmonary circulation produces a reduction in pulmonary blood flow and the pulmonary to systemic blood flow ratio, irrespective of its position. This increases the systemic flow and blood pressure if the ventricular performance remains constant. A rise in ventricular end-diastolic pressure reduces the total cardiac output, pulmonary flow and systemic blood flow with a preserved pulmonary to systemic flow ratio. The absolute reduction in pulmonary flow will exceed the absolute reduction in systemic flow, with its ratio being in proportion to the ratio of systemic to pulmonary vascular resistance. However, a higher pressure will be transmitted distally in these settings. These mechanisms of flow reduction may prevent irreversible pulmonary vascular disease. Distal pulmonary obstruction or elevated ventricular end-diastolic pressure can reduce pulmonary blood flow and may prevent irreversible pulmonary vascular disease. Clinical studies in this direction are recommended for validation.

Aortic Insufficiency during LVAD Support: A Mock Loop Study

Purpose Aortic valve (AoV) insufficiency (AI) is a serious complication in more than 20% of Left Ventricle Assist Device (LVAD) patients within 12 months of LVAD implantation. Normal AoV have developed AI following long-term LVAD support,which has been associated with a significant reduction in LVAD patient survival. During LVAD support, the AoV pressure difference is increased, which reduces systolic opening and worsens regurgitant flow through an incompetent valve. The goal of this study was to measure the effect of LVAD support on intraventricular flow during AI. Methods The velocity field was measured in the midplane of a dilated silicone LV model attached to a rotary LVAD (Abbott Labs, Chicago IL) in a mock circulatory loop. A Pre-LVAD without AI condition (BL) of 20% ejection fraction was established, followed by testing at three LVAD speeds. AI was created with a small 3-D printed stent which was nonobstructive to forward flow but prevented the leaflets from fully closing. LV and aortic pressure, and LVAD and distal aortic flow, were recorded. Results At the Pre-LVAD BL condition, the mean aortic pressure was 63 mmHg and the cardiac output was 2.3 L/min; AI maintained a similar pressure but reduced flow to 1.8 L/min producing a 32% regurgitant fraction (mild-moderate AI). At an LVAD speed of 6400rpm, total systemic flow was 4.3 L/min and 3.1 L/min for BL and AI, respectively, and LVAD flow was 4.2 and 3.6 L/min, producing a 45% regurgitant fraction (moderate-severe AI). The reduction of systemic flow was accompanied by higher LVAD flow, confirming that a regurgitant loop was present. Net forward flow through AoV during BL decreased progressively by 23%, 12% and 0.5% for 4800, 5400, and 6400rpm respectively. AI reduced forward flow and increased backward flow, such that net forward flow was 0.5%, -14%, and -17% at 4800, 5400 and 6400rpm. The AI vena contracta width increased from 2.3 to 3.4 mm as LVAD speed increased. Conclusion Overall, the results showed that an initially mild level of AI worsened with LVAD support prior to any remodeling, simply due to the altered biomechanics of the AoV. These findings provide a foundation for new strategies that can restore AoV biomechanics and reduce the impact of AI on patients with LVAD support.

MR angiography and 2-D phase-contrast imaging for evaluation of meso-rex bypass function.

The meso-Rex bypass restores blood flow to the liver in patients with extrahepatic portal vein thrombosis. Stenosis occurs in some cases, causing the reappearance of portal hypertension. Complications such as thrombocytopenia present on a spectrum and there are currently no guidelines regarding a threshold for endovascular intervention. While Doppler ultrasound (US) is common for routine evaluation, magnetic resonance (MR) angiography with two-dimensional phase-contrast MRI (2-D PC-MRI) may improve the assessment of meso-Rex bypass function. To determine the feasibility and utility of MR angiography with 2-D PC-MRI in evaluating children with meso-Rex bypass and to correlate meso-Rex bypass blood flow to markers of portal hypertension. MR angiography and 2-D PC-MRI in meso-Rex bypass patients were retrospectively analyzed. Minimum bypass diameter was measured on MR angiography and used to calculate cross-sectional area. Meso-Rex bypass blood flow was measured using 2-D PC-MRI and divided by ascending aortic flow to quantify bypass flow relative to systemic circulation. Platelet and white blood cell counts were recorded. Correlation was performed between minimum bypass area, blood flow and clinical data. Twenty-five children (median age: 9.5years) with meso-Rex bypass underwent MR angiography and 2-D PC-MRI. The majority of patients were referred to imaging given clinical concern for complications. Eighteen of the 25 patients demonstrated >50% narrowing of the bypass cross-sectional area. The mean platelet count in 19 patients was 127K/μL. There was a significant correlation between minimum cross-sectional bypass area and bypass flow (rho=0.469, P=0.018) and between bypass flow and platelet counts (r=0.525, P=0.021). Two-dimensional PC-MRI can quantify meso-Rex bypass blood flow relative to total systemic flow. In a cohort of 25 children, bypass flow correlated to minimum bypass area and platelet count. Two-dimensional PC-MRI may be valuable alongside MR angiography to assess bypass integrity.

In Vivo Feasibility Study of an Intra-Atrial Blood Pump for Partial Support of the Left Ventricle.

We are designing an intra-atrial pump (IAP) that will be affixed to the atrial septum and support the compromised left ventricle (LV) in patients with early-stage heart failure without harming the ventricular tissue. It will operate in parallel with the LV, drawing blood from the left atrium and unloading the LV. In previous hydraulic and hemodynamic studies, different blade geometries were tested for the IAP, and the hemodynamic results obtained using a mock circulatory loop showed that the IAP can successfully reduce end-diastolic volume and increase the total systemic flow rate. In the current study, we used a bovine model to validate the in vitro hemodynamic results and better understand how the IAP interacts with the cardiovascular system in vivo. Because this was the first study assessing the complete device in a living system, it was also necessary to determine the best manufacturing techniques and ideal sensor placements. In the bovine model, we were able to successfully implant the IAP across the atrial septum with the outflow graft connected to a peripheral artery. The implanted IAP was capable of providing partial support (1-3 L/min) in vivo. These results indicate that atrial cannulation is feasible and creates a beneficial hemodynamic environment.

Contribution of active atrial contraction to cardiac output in anesthetized American alligators (Alligator mississippiensis).

Ventricular filling may occur directly from the venous circulation during early diastole or via atrial contraction in late diastole. The contribution of atrial contraction to ventricular filling is typically small in mammals (10-40%), but has been suggested to predominate in reptiles. We investigated the importance of atrial contraction in filling of the ventricle in American alligators (Alligator mississippiensis) by bypassing both atria (with the use of ligatures to prevent atrial filling) and measuring the resultant effects on cardiac output in anesthetized animals. Atrial ligation had no significant effects on total systemic blood flow before or after adrenaline injection. Unexpectedly, pulmonary flow was increased following atrial ligation prior to adrenaline treatment, but was unaffected after it. These findings suggest that the atria are non-essential (i.e. redundant) for ventricular filling in alligators, at least under anesthesia, but may serve as important volume reservoirs.

Respiratory Effects on Fontan Circulation During Rest and Exercise Using Real-Time Cardiac Magnetic Resonance Imaging

It is known that respiration modulates cavopulmonary flows, but little data compare mean flows under breath-holding and free-breathing conditions to isolate the respiratory effects and effects of exercise on the respiratory modulation. Real-time phase-contrast magnetic resonance combined with a novel method to track respiration on the same image acquisition was used to investigate respiratory effects on Fontan caval and aortic flows under breath-holding, free-breathing, and exercise conditions. Respiratory phasicity indices that were based on beat-averaged flow were used to quantify the respiratory effect. Flow during inspiration was substantially higher than expiration under the free-breathing and exercise conditions for both inferior vena cava (inspiration/expiration: 1.6 ± 0.5 and 1.8 ± 0.5, respectively) and superior vena cava (inspiration/expiration: 1.9 ± 0.6 and 2.6 ± 2.0, respectively). Changes from rest to exercise in the respiratory phasicity index for these vessels further showed the impact of respiration. Total systemic venous flow showed no significant statistical difference between the breath-holding and free-breathing conditions. In addition, no substantial difference was found between the descending aorta and inferior vena cava mean flows under either resting or exercise conditions. This study demonstrated that inferior vena cava and superior vena cava flow time variance is dominated by respiratory effects, which can be detected by the respiratory phasicity index. However, the minimal respiration influence on net flow validates the routine use of breath-holding techniques to measure mean flows in Fontan patients. Moreover, the mean flows in the inferior vena cava and descending aorta are interchangeable.

Quantification and origin of differential pulmonary blood flow in patients with a Fontan circulation

Methods Patients with a Fontan circulation were prospectively consented to undergo three dimensional phase contrast (4Dflow) imaging during a clinical cardiac MRI evaluation which also included standard two dimensional phase contrast (2D-PC) imaging of all pertinent vessels. Differential pulmonary blood flow was calculated using standard 2D-PC imaging of the right and left pulmonary arteries (RPA and LPA). On the 4Dflow datasets, an expert reader defined cross sections of the RPA, LPA, and the superior and inferior venae cavae (SVC and IVC) within the Fontan circuit using prototype 4Dflow software (Siemens Healthcare, Erlangen, Germany). These defined the analysis and seed planes respectively. Particles were emitted from either the SVC or IVC plane, and quantification was performed at the outlets using the 4Dflow software. The 3D pathlines were then exported for further analysis. Custom software was written in MATLAB (Mathworks, Natick, MA) for flow quantification. The terminal spatial position of each particle was determined. The number of particles that crossed into the RPA and LPA were counted. The differential pulmonary blood flow was calculated for each simulation as the ratio of particles in the RPA to LPA. Internal consistency of the 4Dflow measurements was validated using conservation of mass analysis. Systemic venous flow by origin (IVC or SVC) and total systemic venous flow into each branch PA were calculated. Preferential flow was defined as flow > 70% into one of the branch PAs.