Abstract
Background:
We are developing the Left Atrial Assist Device (LAAD), which is implanted at the mitral position to treat diastolic heart failure (DHF) represented by HFpEF.
Methods:
The LAAD was tested at three pump speeds on a pulsatile mock loop with a pneumatic pump that simulated DHF conditions by adjusting the diastolic drive. The LAAD was implanted in 6 calves, and the hemodynamics were assessed. In three cases, DHF conditions were induced by using a balloon inserted in the left ventricle, and in two cases, mitral valve replacement was also performed after the second aortic cross-clamp.
Results:
DHF conditions were successfully induced with in vitro study. With LAAD support, cardiac output (CO), aortic pressure (AoP), and left atrial pressure (LAP) recovered to normal values, whereas pulsatility was maintained for both in vivo and in vitro studies. Echocardiography showed no left ventricular outflow tract obstruction, and the LAAD was successfully replaced with a mechanical prosthetic valve.
Conclusions:
These initial in vitro and in vivo results support our hypothesis that use of the LAAD increases CO and AoP and decreases LAP, while maintaining arterial pulsatility
Visual Take Home Graphics
In vitro and in vivo development of the Left Atrial Assist Device
LAAD: left atrial assist device, DHF: diastolic heart failure, CO: cardiac output, AoP: arterial pressure, LAP: left atrial pressure, LV: left ventricle.
Lay Summary
The Left Atrial Assist Device (LAAD) is a novel pump, which aims to be a treatment option for heart failure with preserved ejection fraction. Initial in vitro and acute in vivo experiments have been performed, and diastolic heart failure conditions were evaluated.
The LAAD showed improvements in cardiac output and mean aortic pressure with reducing left atrial pressure under normal and diastolic heart failure conditions, while maintaining arterial pulsatility and full function of the aortic valve.
The implantation did not cause left ventricular outflow tract obstruction, and the replacement of the LAAD with a mitral prosthesis was confirmed.
INTRODUCTION
Heart failure (HF) is an epidemic, affecting more than 20 million people worldwide (1). In the United States alone, 6.2 million Americans >20 years old had HF between 2013 and 2016 (2, 3), and by 2030, >8 million people are projected to have HF (4). Among this populations, more than half appear to have preserved systolic function (5, 6); this qualifies their disease decompensation profile as HF with preserved ejection fraction (HFpEF), which has become an increasingly predominant form of the disease (7). The prevalence of this condition is also increasing compared to HF with reduced ejection fraction (HFrEF) (8). HFpEF is a systemic syndrome that is highly heterogeneous, and it goes far beyond just one type of diastolic dysfunction (8, 9). Generally, it has the phenotype of an increase in left ventricular (LV) diastolic pressures, followed by left atrial (LA) pressure (LAP) rise and pulmonary edema, which would lead to noticeable and common symptoms of HF. More specifically, lack of LV compliance limits the Frank-Starling mechanism, which dramatically reduces cardiac output (CO) and leads to hemodynamic morbidity.
Traditionally available therapies for HFrEF have failed to improve the mortality or morbidity of the patients with HFpEF. Also, the prognosis of HFpEF is as poor as it is for HFrEF, sharing similar high mortality and readmission rates (10). While the survival of patients with HFrEF has improved over the past decade (11), that of HFpEF patients has not changed.
Device-based therapies with innovative concepts and tailored to HFpEF patients, are receiving more attention (12). Herein, we report our initial in vitro and in vivo studies aiming to 1) evaluate the Left Atrial Assist Device (LAAD) performance in a mock circulatory loop, and in calves, simulating different levels of diastolic HF (DHF) conditions, and 2) confirm the operational performance and biocompatibility in calves.
METHODS
LAAD Pump
The LAAD has been developed with the unique idea of implantation at the mitral position to pump blood from the LA to properly fill the LV (Figures 1A and 1B). It can mitigate high LAP by draining blood directly from the LA, and it can also offer an immediate increase in CO by providing additional volume to the LV. We have developed the first working prototype of the LAAD and revised its design after several in vivo experimental efforts.
Figure 1. Schematic drawing of the Left Atrial Assist Device (LAAD) concept.
A: A dilated left atrium (LA), thick left ventricular (LV) wall, and small LV cavity in heart failure with preserved ejection fraction (HFpEF). B: The LAAD is implanted in the mitral position to replace the mitral valve.
The latest prototype of the LAAD is shown in Figures 2A, 2B, and 2C, and the schematic illustrations are displayed in Figures 2D, 2E, and 2F, respectively. The dimensions are: diameter, 33.5 mm; height, 33.5 mm, and weight, 39.7 g. This is a mixed-flow pump, and it utilizes a hydrodynamic bearing for radial support of the rotating assembly and a passive magnetic bearing to fix its axial position. The pump is driven by a custom, three-phase, brushless, sensorless DC motor that was designed and built in-house. It is able to pump over a wide operating range (up to 10 L/min and up to 180 mm Hg of pressure rise) to maintain optimal flow in support of CO.
Figure 2. The photos and illustrations of the LAAD.
A: The prototype of the LAAD seen from inlet portion (LA side). B: The side view of the LAAD. Red arrows show the direction of the blood flow created by the LAAD. C: The prototype of the LAAD seen from outlet portion (LV side). D: Schematic illustration of the LAAD seen from LA side. E: Translucent schematic illustration of the LAAD seen from the front. F: Schematic illustration of the LAAD seen from LV side.
Surgically, the LAAD is intended for intracardiac positioning in proximity to the atrioventricular groove, either replacing or on top of the mitral valve (13). The pump housing design underwent minor changes during in vivo experiments to prevent suction events and improve its biocompatibility. The revised pump (Figure 2) has wider inlet portion, and was tested in the last two in vivo experiments, as well as the in vitro experiments.
In Vitro Study
Mock Circulatory Loop
The in vitro mock circulatory loop setup (Figure IA in the Data Supplement) was composed of a pneumatic mock ventricle (AB5000, ABIOMED Inc., Danvers, MA) that simulated the native LV, an adjustable arterial afterload and compliance, LA chamber, and the LAAD (Figure IB in the Data Supplement) that is placed between the LA chamber and the mock ventricle. A mixture of water and glycerin (specific gravity of 1.060) was used as the working fluid to simulate blood. Whenever the LAAD was on, the inflow valve of the AB5000 (working as the mitral valve of the mock ventricle) was secured by a plastic tube (Figure IC in the Data Supplement) that was large enough to keep the inlet valve open (regurgitant) to simulate LAAD implantation at the mitral position (simulating mitral valve resection).
Static Condition
The in vitro testing of the LAAD was performed on the static mock loop with the pneumatic ventricle off to obtain pressure-flow curves at various pump speeds (3,000 rpm, 3,600 rpm, 4,400 rpm, 5,200 rpm, and 6,000 rpm). The pressure was measured just before the LAAD (Pin) and just after the LAAD (Pout). The arterial resistance was changed in 5 or 6 steps to produce a range of LAAD delta pressure (Pout – Pin) conditions.
Pulsatile Condition
The pneumatic ventricle was activated with a pneumatic driving pressure of 200 mm Hg for systole and −35 mm Hg for diastole (negative value indicates a vacuum). The systolic duration was set to 250 msec to simulate a normal heart condition, which generated a CO of approximately 4.0 L/min without the LAAD (which was replaced with a plain straight tube). The arterial compliance and resistance were adjusted to set an aortic pressure (AoP) of 120/80 mm Hg under normal heart conditions and were not changed throughout the entire study.
To simulate three different levels of DHF, the diastolic filling of the pneumatic ventricle was restricted by increasing the diastolic drive pressures of the pneumatic driver from −35 mm Hg at the normal heart condition to 0 mm Hg (mild DHF), +20 mm Hg (moderate DHF), and +40 mm Hg (severe DHF). The systolic drive pressures of the pneumatic driver and the heart rate were kept constant throughout the entire study at 200 mm Hg and 80 bpm, respectively. The AB5000 pneumatic driving pressures were not the same as the actual pressures generated by the system in the flow path.
The LAAD was operated at three different speeds at each DHF condition: 3,600 rpm, 4,400 rpm, and 5,200 rpm. For the basic data without the LAAD, we used a normal competent inflow valve of the AB5000 and a circuit to bypass the LAAD to avoid resistance by the inactive pump.
For each condition, we recorded CO by a flow probe clipped to the outside of the tube (ME20PXL and TS410 Tubing Module, Transonic Systems, Inc., Ithaca, NY). AoP and LAP (which is Pin) were monitored with fluid-filled lines, pressure transducers (13-6615-50; Gould Electronics, Chandler, AZ), and amplifiers (M21018; Honeywell, Charlotte, NC).
In Vivo Study
The study was approved by the Cleveland Clinic’s Institutional Animal Care and Use Committee (#2018-2004). A total of six acute in vivo studies were performed using male Jersey calves (mean body weight: 84.1 ± 11.8 kg). Under general anesthesia with a right lateral position, a central venous pressure (CVP) monitoring line was placed in the left jugular vein. A left thoracotomy was performed on the 4th intercostal space, and an AoP monitoring line was placed in the left internal thoracic artery. A 28-mm flow probe (28PAU113, 28PAX307; Transonic Systems Inc., Ithaca, NY) was placed around the main pulmonary artery to measure CO, and a fluid-filled LAP line was inserted in the LA.
After full heparinization (5 mg/kg), cardiopulmonary bypass (CPB) was started with an arterial cannula in the left carotid artery and a venous cannula in the right ventricle through the main pulmonary artery. The LA was opened after aortic cross-clamping with cardioplegia (modified Buckberg cardioplegia (14)). A patent foramen ovale was observed in one case, and it was closed with a single stitch. The mitral leaflets were resected, and the LAAD was implanted at the mitral annulus with interrupted pledgeted sutures (Figure 3A). The driveline of the LAAD was placed out from the LA incision (Figure 3B) at its closure.
Figure 3. Intraoperative images.
A: The surgical view of the implantation of the LAAD at the mitral position with interrupted pledgeted sutures. A venous return cannula was inserted from the pulmonary artery into the right ventricle. B: The surgical view of the LAAD after implanted at mitral position. The driveline will be fixed in the place of LA closure anastomosis. C: A balloon catheter, which will be inserted from the LV apex. The balloon diameter was approximately 45 mm, inflated with 70 cc of saline. D: The mechanical prosthetic mitral valve of 29 mm was implanted after the LAAD had been removed in the second aortic cross clamp.
A fluid-filled (n = 1) or a micro-manometer Millar catheter (n = 5) was inserted into the LV from the LV free wall near the apex. After de-clamping the aorta, the LAAD was started, and CPB was gradually weaned and then stopped as the LAAD speed was increased. Due to the post-CPB low-output and low blood pressure, dobutamine (2.0 μg/min/kg) was used in one case, and norepinephrine (4-8 mg bolus) was infused in another case before taking data.
After confirming stable conditions, 5-10 minutes from the point of each setting change, the hemodynamic and pump-related data were taken at the pump speeds of 3,600, 4,400, and 5,200 rpm. Epicardial echocardiography was performed to evaluate anatomical fit and to look for any regurgitation through the LAAD.
After the fourth study, we revised the housing design of the pump, especially the inlet section, for prevention of suction events. Additionally, two new procedures were added during the in vivo studies (after collecting the basic LAAD data described above): 1) hemodynamic data measurements during DHF conditions using a balloon catheter inserted from the LV apex and inflated with 50-70 cc saline (Figure 3C) inside the LV cavity (performed in 3 of 6 calves) and, 2) evaluation of the replacement of the LAAD with a mechanical valve replacement, using a 29 mm mechanical bi-leaflet mitral prosthetic valve (500DM29; Medtronic ATS Medical, Inc., Minneapolis, MN) (Figure 3D) after collecting the pump-related data with a second aortic cross-clamping (performed in 2 of 6 calves).
The schematic illustrations of the DHF condition with a balloon and after the mitral valve replacement are illustrated in Figure 4A and 4B, respectively. These additional procedures were performed after repeating the same basic data collection as the previous four in vivo experiments with the revised pump. As for the DHF configuration made by balloon, the baseline data without LAAD with 0 cc, 50 cc, and 70 cc of inflated balloon, had been taken before CPB was started.
Figure 4. Schematic illustrations of in vivo experimental setting.
A: Schematic illustration of in vivo DHF setting. A balloon was inserted from the LV and inflated to 70 cc at most. Red arrows show the blood flow created by the LAAD. An arterial cannula was inserted in the right carotid artery and a venous cannula tip was placed at the RV through the pulmonary artery. B: Schematic illustration of after the mitral valve replacement.
After recording all the data points, the animal was sacrificed with an intravenous bolus injection of Beuthanasia (75 mg/kg). The heart was extracted, and the pump position and any findings inside the LA or LV were evaluated. Although these working prototype of the LAADs were created by 3-D printed parts, the LAAD was disassembled and potential depositions or damages were evaluated.
Data Analysis
All data were recorded at 100 or 200 Hz using a PowerLab data acquisition system (ADInstruments Inc., Colorado Springs, CO), analyzed using LabChart (ADInstruments Inc., Colorado Springs, CO), and then downloaded into Microsoft Excel (Microsoft Corp., Redmond, WA) to summarize and chart the test results.
RESULTS
In Vitro Study
Static Condition
The pressure-flow curves at various pump speeds are shown in Figure II in the Data Supplement. They showed almost straight lines with relatively steep slopes. At 5,200 rpm, the LAAD produced 6 L/min of pump flow at 90 mm Hg of delta pressure.
Pulsatile Condition
Table I in the Data Supplement summarizes the mean CO, mean AoP, mean LAP, and aortic pulse pressure. With the LAAD out of the loop and the mitral valve functioning normally, CO decreased from 4.6 L/min under normal heart condition to 3.4, 2.2, and 1.1 L/min under mild, moderate, and severe DHF conditions, respectively (Figure 5A). With LAAD support at 4,400 rpm, CO recovered to the normal heart condition. Interestingly, at 5,200 rpm, the CO recovered to the same level as normal heart condition regardless of the severity of the three DHF conditions.
Figure 5. The in vitro changes of each parameter by the pump speed, with comparisons among normal heart condition, mild, moderate, and severe DHF conditions.
A: Mean cardiac output (CO), B: Mean arterial pressure (AoP), C: Mean left atrial pressure (LAP), D: Atrial pulse pressure (pulse AoP)
Similar to the results with CO, the mean AoP decreased dramatically from 103 mm Hg under normal heart condition to 69, 46, and 30 mm Hg with mild, moderate, and severe DHF conditions, respectively (Figure 5B). With LAAD support, the AoP recovered to a level of the normal heart condition at 5,200 rpm.
The mean LAP increased dramatically from 4.7 mm Hg for the normal heart condition to 13.5, 18.8, and 20.7 mm Hg for mild, moderate, and severe DHF conditions, respectively (Figure 5C). With LAAD support, the LAP decreased gradually with increasing pump speed and reached a level similar to that of the normal heart condition at 5,200 rpm.
The aortic pulse pressure decreased from 61 mm Hg for the normal heart condition to 57, 44, and 25 mm Hg for mild, moderate, and severe DHF conditions, respectively (Figure 5D). With the LAAD support, the aortic pulse pressure was maintained even at high pump speed.
In Vivo Study
The hemodynamic status during data collection was stable in all animals, and the LAAD responded to all control inputs exactly as expected during the experiment. Table II in the Data Supplement summarizes the mean CO, heart rate, and stroke volume calculated by CO and heart rate. The basic hemodynamic data with the LAAD collected before introducing the DHF conditions were:
CO increased from 5.4 to 6.1 L/min by increasing the pump speed from 3,600 to 4,400 rpm, but stayed nearly the same when the pump flow was increased from 4,400 to 5,200 rpm (Figure 6A).
A similar trend was observed in mean AoP (from 65 to 72 mm Hg, at 3,600 to 4,400 rpm, Figure 6B).
LAP decreased by increasing the pump speed from 3,600 to 5,200 rpm (Figure 6C); however, the LAP values at 5,200 rpm showed a large variation between the experiments, including a negative value (Figure III in the Data Supplement), since pump inlet suctions were observed in some of the studies, although any major hemodynamic influences related the negative value were not observed.
The CVP (Figure 6D) and heart rate remained the same for all the pump speed conditions.
The aortic pulse pressure was essentially maintained throughout the pump speed changes (Figure 6E).
The LV end-diastolic pressure (LVEDP) increased slightly from 3,600 to 4,400 rpm, but stayed the same at high pump speed (Figure 6F).
The typical waveform were displayed in Figure IV in the Data Supplement.
Figure 6. The in vivo changes of each parameter by the pump speed.
A: Mean cardiac output (CO), B: Mean arterial pressure (AoP), C: Mean left atrial pressure (LAP), D: Atrial pulse pressure (pulse AoP), E: Mean left ventricular end-diastolic pressure (LVEDP), F: Mean central venous pressure (CVP)
Epicardial echocardiography showed that the LAAD was in the correct position, with no evidence of obstruction or acceleration of blood flow at the LV outflow tract (Figures VA and VB in the Data Supplement). There was no obvious leakage around the LAAD detected by epicardial echocardiography, and no regurgitant flow through the LAAD was observed.
Mitral valve replacement was performed after the second aorta cross-clamp and explant of the LAAD, without any surgical difficulties. Epicardial echocardiography was conducted again, and showed good positioning of the mechanical valve (Figure VC in the Data Supplement).
As for the DHF conditions, Figure VD in the Data Supplement shows the balloon view (50 cc) obtained by the intraoperative epicardial echocardiography. Each parameter change with balloon (0 cc, 50 cc, and 70 cc) with/without the LAAD, obtained from three in vivo experiments, are shown in Figure VI in the Data Supplement.
Without the LAAD, the balloon inflation caused a decrease in the CO and AoP (Figures VIA, VIB in the Data Supplement). The LAP and LVEDP increase (Figures VIC, VID in the Data Supplement), which could be considered as a configuration similar to DHF, was successfully replicated by balloon inflation inside the LV.
With LAAD support, the differences between each balloon size were reduced in CO, AoP, and LAP (Figures VIA, VIB, and VIC in the Data Supplement). The LVEDP did not increase with balloon inflation even at high LAAD speed (Figure VID in the Data Supplement). The balloon size seemed to not affect the CVP (Figure VIE in the Data Supplement). There was a large difference in the absolute values with and without the LAAD, but this might have been caused by the effect of CPB.
At necropsy, the correct pump position was confirmed from the LA side (Figure VIIA in the Data Supplement) and the LV side (Figures VIIB, VIIC in the Data Supplement). There were no thrombi in the LA or LV. In some of the first four cases, some suction marks were observed, but in the most recent two cases (with revised pump), there was no suction mark found in the LA or LV. The positional relation of the balloon and the LAAD is shown in Figure VIID in the Data Supplement.
The explanted pumps were disassembled and inspected thoroughly by the engineering team. In the first prototype (RD-01) of the LAAD, there were some thrombi and tissues found between the impellers or on the strut ends (Figures VIIIA, VIIIB, VIIIC, and VIIID in the Data Supplement), which could possibly attributed to minor suction events caused by the housing design of the pump. With the subsequent design change of the LAAD (RD-02), there was little to no thrombotic deposition or tissue adhesion observed (Figures VIIIE, VIIIF in the Data Supplement).
DISCUSSION
The results of our initial in vitro and in vivo studies demonstrated that the LAAD increased CO and AoP and decreased LAP under DHF conditions while maintaining arterial pulsatility and full functioning of the aortic valve. We previously reported very similar in vitro results using an investigational, continuous-flow blood pump that is not designed to be implanted at the mitral position, to prove the concept (15). We have now successfully developed an actual working prototype that is implantable at the mitral position and functions as expected. In patients with HFpEF, the LA is typically dilated, LAP is elevated, and increases with exercise. We believe a HFpEF patient would be a potential subject for device treatment with the LAAD.
There are several reports of other devices for HFpEF patients. For instance, Burkhoff et al. (16) proposed Synergy System (Medtronic, Minneapolis, MN), a device to draw blood from the LA and pump it directly into the aorta. In this configuration, the risk of thromboembolism due to blood stagnation in the LV is a concern. And, aortic pulsatility would be remarkably reduced, as we previously reported (15).
There are limited reports using left ventricular assist devices (LVADs) for the HFpEF phenotype (17). Although they have been used for patients with HFrEF (18), the patients with hypertrophic cardiomyopathy or restrictive cardiomyopathy are generally excluded because of the reduced LV end-diastolic dimensions (19) and the perceived risk of suction. The LVAD use with an LA cannulation (20) can prevent an LVAD suction event, but stagnation of blood in the LV and reduced pulsatility would be the same concerns as Synergy System.
Another treatment option to reduce the LAP is to place a shunt between the left and right atria, as represented by the InterAtrial Shunt Device reported by Kaye et al. (21). Clinical trials with interatrial shunts are ongoing but the reduction in the LA pressure reported is very modest.
The LAAD has some advantages in providing a pulsatile flow, directly reducing LAP, filling the LV and the potential of inducing LV remodeling, and less risk of suction due to the high LAP of HFpEF characteristics. Most importantly, all flow paths created by the LAAD follow natural (anatomical and physiological) patterns. Therefore, the LAAD can maintain arterial pulsatility, which may prevent complications such as gastrointestinal bleeding and aortic insufficiency.
One major concern with the pump concept is that the LVEDP could elevate unacceptably through forced filling of the LV. This would cause endocardial ischemia, but in vitro experiments could not evaluate it. Subsequently, we observed the change in LVEDP during the in vivo studies, which did not show much elevation even under the DHF conditions, at least not in these short periods of time. Even with the in vivo data conditions, the influence of post-CPB status might have affected largely on the LVEDP.
As for DHF conditions, we attempted the balloon method for the first time to reduce the LV volume by 50-70 mL. This method showed similar hemodynamics to that of in vitro DHF conditions, and at least, the aspect of the reduced LV volume was considered reproduced. Although the LAAD showed reasonable efficacy under this configurations, the simulated conditions did not completely mimic all the features of HFpEF hemodynamics. Especially, under the DHF conditions, increase in pump speed seemed to have limited influence on LVEDP or CO. The fidelity of the DHF conditions after LAAD implantation seemed to be much more limited than the in vitro results, mainly because of the systolic dysfunction, influence of anesthesia, or right ventricular dysfunction in post-CPB status. We need to evaluate these parameters with chronic studies after at least one week of recovery from the surgical stress and/or the effects of anesthesia, and this would be an important future step.
Nevertheless, since there is no established animal model of DHF or HFpEF having high fidelity, even partial simulation of the hemodynamics is valuable for better understanding of pump performance.
STUDY LIMITATIONS
The major limitation of our in vivo study is that the data were obtained from healthy calves, even though we attempted to introduce DHF conditions. Our new acute DHF model by inflating a balloon inside the LV reduces not only the LV filling but also the LV compliance because the LV cavity is enclosed by a part of the LV wall and a part of very stiff inflated balloon. This model, however, has not been extensively evaluated to simulate DHF. The entire range of potential effects of the LAAD toward hemodynamic parameters in the DHF conditions has not been fully addressed. Moreover, we did not aim to evaluate right heart failure in this series of experiments. The balloon model may also have induced systolic dysfunction; however, we did not aim to differentiate between diastolic and systolic dysfunction by echocardiography at this early stage. To evaluate the accurate capability and incapability of this attempt, evaluations under chronic circumstances that are free from the effects of CPB, anesthesia, and surgery itself, are required.
The second limitation is that pump inlet suctions were observed at high pump speeds in some of the in vivo studies with first prototype (RD-01). Since HFpEF patients typically have enlarged LAs with high LAP, the suction risk seems to be very low. Also, our second prototype (RD-02) has successfully prevented the suction event so far. However, there is potentially some risks of suction events during the recovery phase once the LAAD is implanted in a human. With this concern, replacement of the LAAD with the prosthetic mitral valve were confirmed.
The final limitation is that the biocompatibility evaluation is limited in acute studies, so we will need to perform future chronic studies to confirm the biocompatibility and the requirements for anticoagulation in detail. Also, we will consider how to exteriorize the driveline from LA to a controller outside the body.
CONCLUSIONS
The in vitro data has demonstrated the LAAD capability to increase CO and AoP while decreasing LAP when the systolic function is preserved. The LAAD effectively improved each parameter of DHF models in the in vitro experimental setup. The in vivo study showed feasibility of the pump implantation, and further long-term studies will be necessary to evaluate the stability of LAAD-assisted hemodynamics under DHF conditions and elucidate the design viability in long-term biocompatibility models.
Supplementary Material
Highlights.
The LAAD is a novel pump as a treatment option for patients with HFpEF.
In vitro/in vivo experiments were performed with diastolic dysfunction settings.
Improvements in hemodynamics were showed by the LAAD, maintaining pulsatility.
The LAAD implantation did not cause left ventricular outflow tract obstruction.
Replaceability of the LAAD with a mitral prosthesis was confirmed.
Sources of Funding:
This study was supported by funding from National Heart, Lung and Blood Institute, National Institutes of Health (NIH), NIH Center for Accelerated Innovation at Cleveland Clinic (NCAI-CC), (NIH-NHLBI 1UH54HL119810; NCAI-19-12-APP-CCF).
Abbreviations
- HF
heart failure
- HFpEF
heart failure with preserved ejection fraction
- HFrEF
heart failure with reduced ejection fraction
- LV
left ventricular
- LA
left atrial
- LAP
left atrial pressure
- CO
cardiac output
- DHF
diastolic heart failure
- LAAD
left atrial assist device
- AoP
aortic pressure
- CPB
cardiopulmonary bypass
Footnotes
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