- Email: [email protected]
Left atrial assist device to treat patients with heart failure with preserved ejection fraction: Initial in vitro study
Journal Pre-proof Left Atrial Assist Device to Treat Patients with Heart Failure with Preserved Ejection Fraction: Initial in Vitro Study Kiyotaka Fukamachi, MD, PhD, David J. Horvath, MSME, Jamshid H. Karimov, MD, PhD, Yuichiro Kado, MD, PhD, Takuma Miyamoto, MD, PhD, Barry D. Kuban, BS, Randall C. Starling, MD, MPH PII:
S0022-5223(20)30211-7
DOI:
https://doi.org/10.1016/j.jtcvs.2019.12.110
Reference:
YMTC 15633
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 27 August 2019 Revised Date:
25 December 2019
Accepted Date: 31 December 2019
Please cite this article as: Fukamachi K, Horvath DJ, Karimov JH, Kado Y, Miyamoto T, Kuban BD, Starling RC, Left Atrial Assist Device to Treat Patients with Heart Failure with Preserved Ejection Fraction: Initial in Vitro Study, The Journal of Thoracic and Cardiovascular Surgery (2020), doi: https:// doi.org/10.1016/j.jtcvs.2019.12.110. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020 Published by Elsevier Inc. on behalf of The American Association for Thoracic Surgery
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Original Manuscript
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Title: Left Atrial Assist Device to Treat Patients with Heart Failure with Preserved Ejection
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Fraction: Initial in Vitro Study
5 6
Kiyotaka Fukamachi, MD, PhDa; David J Horvath, MSMEb; Jamshid H. Karimov, MD, PhDa;
7
Yuichiro Kado, MD, PhDa; Takuma Miyamoto, MD, PhDa; Barry D. Kuban, BSa,c; Randall C.
8
Starling, MD, MPHd,e
9 10
a
11
b
12
c
13
d
14
Clinic
15
e
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic R1 Engineering, Euclid, Ohio
Electronics Core, Medical Device Solutions, Lerner Research Institute, Cleveland Clinic Department of Cardiovascular Medicine, Miller Family Heart and Vascular Institute, Cleveland
Kaufman Center for Heart Failure, Cleveland Clinic
16 17
Conflict of Interest: Kiyotaka Fukamachi, David J. Horvath, Jamshid H. Karimov, and Randall
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C. Starling are co-inventors of the LAAD. The other coauthors have nothing to disclose.
19 20
Sources of Funding: This study was supported by Cleveland Clinic internal funding from the
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Department of Biomedical Engineering, Lerner Research Institute.
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Address for correspondence:
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Kiyotaka Fukamachi, MD, PhD
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Department of Biomedical Engineering/ND20
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Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195
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Tel: 216 445 9344; Fax: 216 444 9198; E-mail: [email protected]
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Total word count: 3,498 (4,079 - 249 - 332) words Limit = 3,500 (excludes the abstract and
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references)
32 33
Presented at the American College of Cardiology's 68th Annual Scientific Session, March 16-18,
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2019, in New Orleans, LA
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Glossary of Abbreviations
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Ao ≡ aorta
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AoP ≡aortic pressure
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CO ≡ cardiac output
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DHF ≡diastolic heart failure
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HFpEF ≡ heart failure with preserved ejection fraction
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HFrEF ≡heart failure with reduced ejection fraction
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LA ≡ left atrium (or left atrial)
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LAAD ≡Left Atrial Assist Device
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LAP ≡left atrial pressure
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LV ≡left ventricle (or left ventricular)
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LVAD ≡left ventricular assist device
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Central Message (199 characters) (200 character limit including spaces)
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The initial in vitro results of a Left Atrial Assist Device for patients with heart failure with
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preserved ejection fraction showed improvement of hemodynamics while maintaining arterial
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pulsatility.
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Perspective Statement (403 characters) (405 character limit including spaces)
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There is no effective therapy available for patients with heart failure with preserved ejection
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fraction (HFpEF), and the prognosis is poor. The successful initial in vitro study of the LAAD
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demonstrated a significant potential for a valid clinical option for HFpEF patients. Further
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developments are necessary to demonstrate its efficacy and safety in animal models before its
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applications to humans.
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Abstract (249 words)
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Objectives: Many patients with heart failure have preserved ejection fraction but also diastolic
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dysfunction, with no effective therapy. We are developing a new pump (Left Atrial Assist
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Device, LAAD) for implantation at the mitral position to pump blood from the left atrium to
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sufficiently fill the left ventricle. The purpose of the initial in vitro study was to demonstrate that
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the LAAD can reduce left atrial pressure (LAP) and increase cardiac output (CO) while
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maintaining arterial pulsatility and normal aortic valve function using a proof of concept device.
68 69
Methods: The LAAD concept was tested at three pump speeds on a pulsatile mock loop with a
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pneumatic pump that simulated the normal function of the native ventricle as well as three levels
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of diastolic heart failure (DHF-1, -2, and -3) by adjusting the diastolic drive pressure to limit
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diastolic filling of the ventricle.
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Results: Without the LAAD, CO and aortic pressure (AoP) decreased dramatically from 3.8
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L/min and 100 mm Hg at normal heart condition to 1.2 L/min and 35 mm Hg at DHF-3,
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respectively. With LAAD support, both CO and AoP recovered to normal heart values at 3,200
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rpm and surpassed normal heart values at 3,800 rpm. Furthermore, with LAAD support, LAP
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recovered to almost that of the normal heart condition at 3,800 rpm.
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Conclusion: These initial in vitro results support our hypothesis that use of the LAAD increases
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CO and AoP and decreases LAP under DHF conditions while maintaining arterial pulsatility and
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full function of the aortic valve.
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INTRODUCTION Heart failure is a major public health concern and one of the most common reasons for
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hospitalization. Heart failure is also a primary contributor to global cardiovascular mortality,
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affecting approximately 23 million people,1, 2 and its prevalence is rapidly rising, even in
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developing nations.3 More than 5.1 million Americans 20 years of age or older have heart
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failure, and more than 8 million Americans will be living with heart failure by 2030.4 Heart
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failure is a multifactorial systemic disease in which the associated cardiac injury activates
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structural, neurohumoral, cellular, and molecular mechanisms that attempt to maintain
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physiological function by acting as a network.5
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Currently, approximately 50-60% of heart failure patients have preserved systolic
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function, known as heart failure with preserved ejection fraction (HFpEF), and the prevalence of
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this condition is increasing. HFpEF is a systemic syndrome that goes far beyond just diastolic
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dysfunction and is heterogeneous;6, 7 however, it is typically associated with an increase in left
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ventricular (LV) diastolic pressures. More specifically, this disease is related to LV stiffness and
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impaired relaxation: a lack of LV compliance limits the Frank-Starling mechanism, which
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dramatically reduces cardiac output (CO) and leads to hemodynamic morbidity. An increase in
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LV stiffness often manifests as pulmonary edema due to the high left atrial pressure (LAP),
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which adds complexity to managing the disease. There is no effective therapy available for
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patients with this condition, and the prognosis is poor. Therapies that are effective for patients
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with systolic heart failure (heart failure with reduced ejection fraction, or HFrEF) have failed in
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patients with HFpEF. For example, LV assist devices (LVADs) that work for patients with
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HFrEF do not work well for patients with HFpEF as the LV cavity is small and its volume is
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insufficient for an LVAD to work effectively.
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We are developing a new pump (Left Atrial Assist Device, LAAD) for implantation at
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the mitral position to pump blood from the left atrium (LA) to properly fill the LV (Figure 1).
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The major advantage of the LAAD is that it can directly address the symptoms of HFpEF: high
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LAP, associated pulmonary congestion, and low LV volume, thereby providing an immediate
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increase in CO and improving the clinical condition of patients with HFpEF. The purpose of the
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initial in vitro study was to prove the concept that use of the LAAD can reduce LAP and increase
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CO while maintaining arterial pulsatility under diastolic heart failure (DHF) conditions when
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systolic function is preserved. For comparison, the same proof of concept device was evaluated
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as an LVAD (pumping from the LV to the aorta (Ao)) and also as a bypass from the LA to the
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aorta (LA-Ao).
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METHODS
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LAAD PERFORMANCE IN A MOCK CIRCULATORY LOOP
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We are currently developing a working prototype of the LAAD that can be implanted in
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the mitral position as shown in Figure 1; however, in this proof of concept study, we used an
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investigational, continuous-flow blood pump (proof of concept device) with specifications based
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on requirements for right ventricular support, as it has a suggested operational range suitable for
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mechanical support proposed in HFpEF. The LAAD is intended for intracardiac positioning in
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proximity to the atrio-ventricular groove. It will have a hybrid magnetic and hydrodynamic
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bearing and will be able to pump over a wide operating range to maintain optimal flow in
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support of cardiac output. The drive line will exit from the LA.
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The in vitro mock circulatory loop setup was comprised of a pneumatic mock ventricle (AB5000, ABIOMED Inc., Danvers, MA) that simulated the native LV, an adjustable arterial
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afterload and compliance, LA reservoir, and a continuous-flow, proof of concept device that is
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placed between the LA reservoir and the mock ventricle as the LAAD (Figure 2A). The pump
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flow is equal to CO and the total flow. To simulate blood, a mixture of water and glycerin
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(specific gravity, 1.060) was used as the working fluid.
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To simulate three different levels of DHF, the diastolic filling of the pneumatic ventricle
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was restricted by increasing the diastolic drive pressures of the pneumatic driver from -44 mm
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Hg at the normal heart condition to +15 mm Hg (DHF-1), +25 mm Hg (DHF-2), and +40 mm
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Hg (DHF-3). The systolic drive pressures of the pneumatic driver and the heart rate were kept
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constant during the entire study at 170 mm Hg and 80 bpm, respectively, with the systolic
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duration set to 250 msec. The compliance and resistance of the systemic circulation was
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adjusted to have an aortic pressure (AoP) of 120/80 mmHg under normal heart condition
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(systolic/diastolic = 170/-44 mm Hg), which generated a CO of approximately 4.0 L/min without
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activation of the LAAD.
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The LAAD was operated at three different speeds at each DHF condition: low (2,600
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rpm), middle (3,200 rpm), and high (3,800 rpm). When the LAAD was on, a tube was secured
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within the inflow valve housing of the AB5000 that was large enough to keep the inlet valve
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open (regurgitant) to simulate LAAD implantation at the mitral position (no mitral valve). When
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the data were taken without the LAAD, we used a normal competent inflow valve and a circuit to
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bypass the LAAD to avoid resistance of the pump when it was not active.
148 149 150 151
LA-AO PERFORMANCE IN A MOCK CIRCULATORY LOOP The same mock loop that was used for LAAD evaluation was used to evaluate LA-AO performance; however, the outflow of the centrifugal pump was connected not to the LV but to
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the Ao, bypassing the LV (Figure 2B). A normal competent inflow valve was used. In this LA-
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Ao configuration, the total flow is the sum of the pump flow and CO. Similar to the LAAD
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study, the data were taken at normal heart conditions and three levels of DHF at three pump
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speeds, 2,800, 3,200, and 3,800 rpm.
156 157 158
LVAD PERFORMANCE IN A MOCK CIRCULATORY LOOP The same mock loop as for the LAAD evaluation was used to evaluate LVAD
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performance; however, the inflow of the centrifugal pump was connected not to the LA reservoir
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but to an additional outlet of the pneumatic ventricle’s chamber that was created to simulate LV
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apex cannulation, similar to the clinical LVADs (Figure 2C). A normal competent inflow valve
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was used. In this LVAD configuration, the total flow is the sum of the pump flow and CO.
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Similarly to the LAAD study, the data were taken at normal heart condition and three levels of
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DHF, with pump speeds of 2,800, 3,200, and 3,800 rpm.
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DATA ACQUISITION AND ANALYSIS
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For each condition, we recorded pump flow and total flow (this is equal to CO in the
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LAAD configuration) using ultrasonic flow probes and flow meters (20XL, 10XL and T110,
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Transonic Systems, Inc., Ithaca, NY). Ultrasonic flow probes were clamped onto the ½ inch
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inner diameter pump outflow tubing and on the 1 inch inner diameter loop tubing between the
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compliance chamber and the reservoir. Pressures were monitored with fluid-filled lines
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connected at the LA reservoir and Ao.
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All data were recorded at 200 Hz using a PowerLab data acquisition system (ADInstruments Inc., Colorado Springs, CO), analyzed using LabChart (ADInstruments Inc.,
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Colorado Springs, CO), and then downloaded into Microsoft Excel (Microsoft Corp., Redmond,
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WA) to summarize and chart the test results.
177 178 179
RESULTS
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LAAD CONFIGURATION
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With the LAAD pump off, CO decreased dramatically from 3.8 L/min with normal heart
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condition to 2.4, 2.0, and 1.2 L/min under DHF-1, DHF-2, and DHF-3, respectively (Figure 3A).
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With LAAD support, CO (or the total flow) recovered to a level slightly below that of the normal
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heart condition with the LAAD support at 3,200 rpm and surpassed that of normal heart
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condition at 3,800 rpm. It is interesting that the CO recovery was similar among the DHF-1,
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DHF-2, and DHF-3 conditions, although the CO without pump support was very different. At
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low pump speed (2,600 rpm) under normal heart condition, the CO decreased to 3.6 L/min from
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the 3.8 L/min that was observed with the pump off, which was due to the mitral regurgitation
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that was confirmed with the pump flow waveform.
190
Similarly to CO, the mean AoP decreased dramatically from 100 mm Hg under normal
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heart condition to 59, 49, and 35 mmHg with DHF-1, DHF-2, and DHF-3, respectively, with the
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LAAD pump off (Figure 3B). With LAAD support, the AoP recovered to a level that almost
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reached that of the normal heart condition at 3,200 rpm and surpassed the normal heart condition
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(by 20 mm Hg) at 3,800 rpm. It is again interesting that the recovery of the AoP was very
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similar among DHF-1, DHF-2, and DHF-3, although the AoP values without pump support were
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very different.
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The mean LAP increased from 16.3 mm Hg for the normal heart condition to 21.6, 22.6,
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and 23.4 mm Hg for DHF-1, DHF-2, and DHF-3, respectively (Figure 3C). With LAAD
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support, the LAP recovered to a level that was similar to that of the normal heart condition at
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3,800 rpm. It is again interesting that the recovery of the LAP was very similar among DHF-1,
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DHF-2, and DHF-3, although the LAP values without pump support were very different.
202 203
COMPARISON OF LAAD DATA WITH THE LA-AO CONFIGURATION AND THE LVAD
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CONFIGURATION
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Figure 4 compares the results of the LAAD configuration with those of the LA-Ao and
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LVAD configurations at a pump speed of 3,200 rpm. The total flow was similar between the
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LAAD and LA-Ao configurations but was lower with the LVAD configuration under DHF
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conditions (Figure 4A) due to the fact that the volume in the LV was limited, as in to the clinical
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situation for DHF. The mean AoP followed a similar trend to the total flow (Figure 4B). The
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mean LAP was higher under the LA-Ao and LVAD configurations compared with that with the
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LAAD under DHF conditions (Figure 4C).
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Figure 5 compares the results of the LAAD with those of the LA-Ao configuration in
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more detail at three different pump speeds. The total flow increased as the pump speed increased
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very similarly in the LAAD and LA-Ao configurations (Figure 5A). The results of mean AoP
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reflected those of the total flow (Figure 5B). A large difference was observed in the arterial
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pulse pressure (Figure 5C). Whereas the arterial pulse pressure was maintained with the LAAD
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configuration, it decreased as the pump speed increased with the LA-Ao configuration. This low
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pulsatility is a limitation of the LA-Ao configuration and is also a concern for potential
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thromboembolisms due to blood stagnation in the LV.8 With the LAAD, the entire flow goes
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from the LV through the aortic valve to keep the valve fully in action, while the aortic valve is
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always closed in the LA-Ao configuration, which may cause a fusion of the aortic valve cusps,
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aortic valve regurgitation, and/or thrombus in the aortic root due to blood stagnation.
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Discussion These results demonstrated that the LAAD increased CO and AoP and decreased LAP
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under DHF conditions while maintaining arterial pulsatility and full function of the aortic valve.
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Despite the multifactorial origin of HFpEF, patient conditions can be improved by addressing
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LV filling, which is the mechanism of action for this proposed new device solution. In these
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patients, the LV cavity is small due to thickened and stiffened LV muscle (impaired compliance)
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(Figure 1). The LA is typically dilated, and LAP is elevated, because it requires much force
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(pressure) for the LA to pump blood to the stiffened LV. This physiology is similar to that of
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mitral stenosis, but the LV cavity, instead of the mitral valve, is the stenotic object. Therefore,
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we believe a typical HFpEF candidate would be a suitable recipient for the LAAD. Dilatation of
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the LV cavity and increase in LV compliance are the primary therapy for this physiology but are
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very difficult to achieve.
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Drawing blood from the LA and pumping it into the aorta has been considered;9 however,
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thromboembolism would be an issue in this configuration due to blood stagnation in the LV, and
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LV remodeling would be unlikely to occur. We evaluated this configuration and demonstrated
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reduced pulsatility with higher pump speeds (Figure 5C), which could be another limitation of
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this pump placement. LVADs have been successfully used for patients with HFrEF;10 however,
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patients with hypertrophic cardiomyopathy or restrictive cardiomyopathy are generally excluded
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from LVAD therapy because of the reduced LV end-diastolic dimensions seen in these patients11
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and perceived risk of suction with continuous-flow LVADs. In this study, we demonstrated that
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an LVAD did not support DHF patients well due to small LV volume (Figure 4).
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Another possible treatment for HFpEF patients is to place a shunt between the left and
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right atria to reduce LAP and LV end-diastolic pressure.12 However, pulmonary capillary wedge
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pressure, a surrogate for LA pressure, was reduced by only 2 mm Hg (from 19 ± 6 mm Hg to 17
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± 6 mm Hg) at 12 months after interatrial shunt device implantation, and there was no reduction
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in the mean pulmonary arterial pressure (from 25 ± 8 mm Hg to 26 ± 8 mm Hg). Furthermore,
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this method is not likely to increase CO or promote LV remodeling.
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The LAAD can be operated at a constant pump speed as well as with pump speed
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modulation (co-pulsation, counterpulsation, or asynchronous mode). In constant speed mode,
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the pump flow is higher during diastole due to a low pressure difference (LVP – LAP) and lower
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during systole due to a higher pressure difference. Importantly, all flow paths created by the
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LAAD follow natural (anatomical and physiological) patterns.
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STUDY LIMITATIONS
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There are limitations to this study. One of the concerns regarding LAAD support is an
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increase in the LV pressure during diastole that may affect coronary flows. In this mock loop
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with a pneumatic ventricle, the LV pressure during diastole showed very flat pressures (not
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shown) equal to the diastolic pneumatic driving pressures at each condition (normal heart (-44
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mm Hg), DHF-1 (+15 mm Hg), DHF-2 (+25 mm Hg), and DHF-3 (+40 mm Hg)) until the
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diaphragm contacted the housing (full filling). This is because these two chambers (LV fluid
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chamber and pneumatic chamber) are separated only by a thin diaphragm. In addition, there is
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no additional increase in LV volume once the diaphragm contacts the housing. Furthermore, the
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diastolic drive pressure of the pneumatic ventricle was constant during each of the three different
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degrees of diastolic dysfunction and therefore does not adequately simulate dynamic LV
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diastolic dysfunction. We need an animal study to see the effects of potential elevation of the
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LV end-diastolic pressure on coronary blood flow and also to evaluate right ventricular function
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due to ventricular interdependence. Another limitation is that the LAP at the normal heart
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condition without LAAD was higher (16.3 mm Hg) than the expected physiologic range and
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increased only moderately while there were marked decreases in CO and mean AoP under DHF
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conditions, which are not typically seen in HFpEF patients. HFpEF has many phenotypes and
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co-morbidities hence the applicability of this new device broadly versus a more narrow patient
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population must be determined. We believe that the relative change in LAP will not be affected
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by this relatively high value. Finally, our model did not include a simulation of the LA
278
contractility, which may play an important role in the LAAD configuration.
279 280
CONCLUSIONS
281
These initial in vitro study results support our hypothesis that use of the LAAD increases
282
CO and AoP and decreases LAP under DHF conditions while maintaining arterial pulsatility and
283
full function of the aortic valve. Our model simulates the human physiology of HFpEF. If the
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animal model proves feasible the potential for effective hemodynamic treatment in humans with
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disease will be significant.
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References
290
1.
Go AS, Mozaffarian D, Roger VL, et al. American Heart Association Statistics
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Committee, and Stroke Statistics Subcommittee. Executive summary: heart disease and
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stroke statistics--2014 update: a report from the American Heart Association. Circulation.
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2014;129:399-410. PMCID: PMC2891613.
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2.
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failure: public and private health burden. Eur Heart J. 1998;19 Suppl P:P9-16. 3.
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McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart
Braunwald E. Research advances in heart failure: a compendium. Circ Res. 2013;113:633-645.
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Heidenreich PA, Albert NM, Allen LA, et al. American Heart Association Advocacy
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Coordinating Committee, Council on Arteriosclerosis Thrombosis, Vascular Biology,
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Council on Cardiovascular Radiology, Intervention, Council on Clinical Cardiology,
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Council on Epidemiology and Prevention; troke Council. Forecasting the impact of heart
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failure in the United States: a policy statement from the American Heart Association.
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Circ Heart Fail. 2013;6:606-619. PMCID: PMC3908895.
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Tanai E, Frantz S. Pathophysiology of Heart Failure. Compr Physiol. 2015;6:187-214.
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Misbah R, Fukamachi K. Heart failure with preserved ejection fraction: A review for the
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clinician. J Cardiol Cardiovasc Ther (in press). 7.
Xanthopoulos A, Triposkiadis F, Starling RC. Heart failure with preserved ejection
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fraction: Classification based upon phenotype is essential for diagnosis and treatment.
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Trends Cardiovasc Med. 2018;28:392-400.
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8.
Reilly MP, Wiegers SE, Cucchiara AJ, et al. Frequency, risk factors, and clinical
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outcomes of left ventricular assist device-associated ventricular thrombus. Am J Cardiol.
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2000;86:1156-1159, A1110.
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9.
Burkhoff D, Maurer MS, Joseph SM, et al. Left atrial decompression pump for severe
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heart failure with preserved ejection fraction: theoretical and clinical considerations.
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JACC Heart Fail. 2015;3:275-282.
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10.
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Levitated Cardiac Pump in Heart Failure. N Engl J Med. 2018;378:1386-1395. 11.
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Mehra MR, Goldstein DJ, Uriel N, et al. Two-Year Outcomes with a Magnetically
Lund LH, Matthews J, Aaronson K. Patient selection for left ventricular assist devices. Eur J Heart Fail. 2010;12:434-443.
12.
Kaye DM, Hasenfuss G, Neuzil P, et al. One-Year Outcomes After Transcatheter
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Insertion of an Interatrial Shunt Device for the Management of Heart Failure With
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Preserved Ejection Fraction. Circ Heart Fail. 2016;9.
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Figure Legends
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Figure 1. Schematic drawing of the Left Atrial Assist Device (LAAD) concept. A: A dilated
326
left atrium (LA), thick left ventricular (LV) wall, and small LV cavity in heart failure
327
with preserved ejection fraction (HFpEF) are shown. B: The LAAD is implanted in
328
the mitral position to replace the mitral valve of a HFpEF patient to pump blood from
329
the LA to properly fill the LV.
330
Figure 2. Schematic drawing of the three pump configurations. A: For the Left Atrial Assist
331
Device (LAAD) configuration, the pump is placed between the left atrial chamber
332
and the pneumatic ventricle. In this configuration, pump flow is equal to cardiac
333
output and the total flow. B: For the left atrium-to-aorta (LA-Ao) configuration, the
334
pump is placed between the left atrial chamber and the aorta, bypassing the pneumatic
335
ventricle. In this configuration, the total flow is the sum of the pump flow and the
336
cardiac output. C: For the left ventricular assist device (LVAD) configuration, the
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pump is placed between the pneumatic ventricle and the aorta, similar to a clinical
338
LVAD. In this configuration, the total flow is the sum of the pump flow and cardiac
339
output. AoP – aortic pressure; LAP – left atrial pressure.
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Figure 3. Cardiac output, mean aortic pressure (AoP), and mean left atrial pressure (LAP) vs.
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Left Atrial Assist Device (LAAD) pump speed (or off) under normal heart condition
342
and three levels of diastolic heart failure (DHF) conditions. A: With the LAAD pump
343
off, cardiac output decreased dramatically as DHF progressed. With LAAD support,
344
cardiac output recovered to almost that of the normal heart condition with LAAD
345
support at 3,200 rpm and surpassed that of the normal heart condition at 3,800 rpm
346
under all three levels of DHF. B: Mean AoP results were similar to those of cardiac
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output. C: With the LAAD off, the mean LAP increased as DHF progressed. With
348
LAAD support, the mean LAP almost reached that of the normal heart condition at
349
3,800 rpm.
350
Figure 4. Total flow, mean aortic pressure (AoP), and mean left atrial pressure (LAP) for three
351
different configurations at a pump speed of 3,200 rpm. A: The total flow was similar
352
between the Left Atrial Assist Device (LAAD) and left atrium-to-aorta (LA-Ao)
353
configuration but was lower for the left ventricular assist device (LVAD)
354
configuration under diastolic heart failure (DHF) conditions. B: The mean AoP
355
followed a trend similar to that of the total flow. C: The mean LAP was higher for
356
the LA-Ao and LVAD configurations compared with the LAP for the LAAD under
357
DHF conditions.
358
Figure 5. Total flow, mean aortic pressure (AoP), and arterial pulse pressure for the Left Atrial
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Assist Device (LAAD) and left atrium-to-aorta (LA-Ao) configuration at three
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different pump speeds and the two most severe diastolic heart failure (DHF)
361
conditions. A: The total flow increased as the pump speed increased in both the
362
LAAD and LA-Ao configurations. B: Mean AoP showed a trend similar to that of
363
the total flow. C: Whereas the arterial pulse pressure was maintained with the LAAD
364
configuration, it decreased as the pump speed increased for the LA-Ao configuration.
365
Central Picture. Schematic drawing of the LAAD implanted in the mitral position of a HFpEF
366 367
patient.
S0022-5223(20)30211-7
DOI:
https://doi.org/10.1016/j.jtcvs.2019.12.110
Reference:
YMTC 15633
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 27 August 2019 Revised Date:
25 December 2019
Accepted Date: 31 December 2019
Please cite this article as: Fukamachi K, Horvath DJ, Karimov JH, Kado Y, Miyamoto T, Kuban BD, Starling RC, Left Atrial Assist Device to Treat Patients with Heart Failure with Preserved Ejection Fraction: Initial in Vitro Study, The Journal of Thoracic and Cardiovascular Surgery (2020), doi: https:// doi.org/10.1016/j.jtcvs.2019.12.110. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020 Published by Elsevier Inc. on behalf of The American Association for Thoracic Surgery
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Original Manuscript
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Title: Left Atrial Assist Device to Treat Patients with Heart Failure with Preserved Ejection
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Fraction: Initial in Vitro Study
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Kiyotaka Fukamachi, MD, PhDa; David J Horvath, MSMEb; Jamshid H. Karimov, MD, PhDa;
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Yuichiro Kado, MD, PhDa; Takuma Miyamoto, MD, PhDa; Barry D. Kuban, BSa,c; Randall C.
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Starling, MD, MPHd,e
9 10
a
11
b
12
c
13
d
14
Clinic
15
e
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic R1 Engineering, Euclid, Ohio
Electronics Core, Medical Device Solutions, Lerner Research Institute, Cleveland Clinic Department of Cardiovascular Medicine, Miller Family Heart and Vascular Institute, Cleveland
Kaufman Center for Heart Failure, Cleveland Clinic
16 17
Conflict of Interest: Kiyotaka Fukamachi, David J. Horvath, Jamshid H. Karimov, and Randall
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C. Starling are co-inventors of the LAAD. The other coauthors have nothing to disclose.
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Sources of Funding: This study was supported by Cleveland Clinic internal funding from the
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Department of Biomedical Engineering, Lerner Research Institute.
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Address for correspondence:
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Kiyotaka Fukamachi, MD, PhD
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Department of Biomedical Engineering/ND20
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Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195
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Tel: 216 445 9344; Fax: 216 444 9198; E-mail: [email protected]
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Total word count: 3,498 (4,079 - 249 - 332) words Limit = 3,500 (excludes the abstract and
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references)
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Presented at the American College of Cardiology's 68th Annual Scientific Session, March 16-18,
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2019, in New Orleans, LA
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Glossary of Abbreviations
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Ao ≡ aorta
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AoP ≡aortic pressure
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CO ≡ cardiac output
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DHF ≡diastolic heart failure
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HFpEF ≡ heart failure with preserved ejection fraction
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HFrEF ≡heart failure with reduced ejection fraction
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LA ≡ left atrium (or left atrial)
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LAAD ≡Left Atrial Assist Device
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LAP ≡left atrial pressure
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LV ≡left ventricle (or left ventricular)
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LVAD ≡left ventricular assist device
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Central Message (199 characters) (200 character limit including spaces)
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The initial in vitro results of a Left Atrial Assist Device for patients with heart failure with
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preserved ejection fraction showed improvement of hemodynamics while maintaining arterial
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pulsatility.
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Perspective Statement (403 characters) (405 character limit including spaces)
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There is no effective therapy available for patients with heart failure with preserved ejection
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fraction (HFpEF), and the prognosis is poor. The successful initial in vitro study of the LAAD
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demonstrated a significant potential for a valid clinical option for HFpEF patients. Further
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developments are necessary to demonstrate its efficacy and safety in animal models before its
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applications to humans.
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Abstract (249 words)
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Objectives: Many patients with heart failure have preserved ejection fraction but also diastolic
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dysfunction, with no effective therapy. We are developing a new pump (Left Atrial Assist
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Device, LAAD) for implantation at the mitral position to pump blood from the left atrium to
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sufficiently fill the left ventricle. The purpose of the initial in vitro study was to demonstrate that
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the LAAD can reduce left atrial pressure (LAP) and increase cardiac output (CO) while
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maintaining arterial pulsatility and normal aortic valve function using a proof of concept device.
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Methods: The LAAD concept was tested at three pump speeds on a pulsatile mock loop with a
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pneumatic pump that simulated the normal function of the native ventricle as well as three levels
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of diastolic heart failure (DHF-1, -2, and -3) by adjusting the diastolic drive pressure to limit
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diastolic filling of the ventricle.
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Results: Without the LAAD, CO and aortic pressure (AoP) decreased dramatically from 3.8
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L/min and 100 mm Hg at normal heart condition to 1.2 L/min and 35 mm Hg at DHF-3,
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respectively. With LAAD support, both CO and AoP recovered to normal heart values at 3,200
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rpm and surpassed normal heart values at 3,800 rpm. Furthermore, with LAAD support, LAP
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recovered to almost that of the normal heart condition at 3,800 rpm.
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Conclusion: These initial in vitro results support our hypothesis that use of the LAAD increases
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CO and AoP and decreases LAP under DHF conditions while maintaining arterial pulsatility and
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full function of the aortic valve.
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INTRODUCTION Heart failure is a major public health concern and one of the most common reasons for
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hospitalization. Heart failure is also a primary contributor to global cardiovascular mortality,
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affecting approximately 23 million people,1, 2 and its prevalence is rapidly rising, even in
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developing nations.3 More than 5.1 million Americans 20 years of age or older have heart
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failure, and more than 8 million Americans will be living with heart failure by 2030.4 Heart
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failure is a multifactorial systemic disease in which the associated cardiac injury activates
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structural, neurohumoral, cellular, and molecular mechanisms that attempt to maintain
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physiological function by acting as a network.5
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Currently, approximately 50-60% of heart failure patients have preserved systolic
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function, known as heart failure with preserved ejection fraction (HFpEF), and the prevalence of
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this condition is increasing. HFpEF is a systemic syndrome that goes far beyond just diastolic
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dysfunction and is heterogeneous;6, 7 however, it is typically associated with an increase in left
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ventricular (LV) diastolic pressures. More specifically, this disease is related to LV stiffness and
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impaired relaxation: a lack of LV compliance limits the Frank-Starling mechanism, which
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dramatically reduces cardiac output (CO) and leads to hemodynamic morbidity. An increase in
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LV stiffness often manifests as pulmonary edema due to the high left atrial pressure (LAP),
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which adds complexity to managing the disease. There is no effective therapy available for
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patients with this condition, and the prognosis is poor. Therapies that are effective for patients
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with systolic heart failure (heart failure with reduced ejection fraction, or HFrEF) have failed in
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patients with HFpEF. For example, LV assist devices (LVADs) that work for patients with
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HFrEF do not work well for patients with HFpEF as the LV cavity is small and its volume is
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insufficient for an LVAD to work effectively.
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We are developing a new pump (Left Atrial Assist Device, LAAD) for implantation at
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the mitral position to pump blood from the left atrium (LA) to properly fill the LV (Figure 1).
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The major advantage of the LAAD is that it can directly address the symptoms of HFpEF: high
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LAP, associated pulmonary congestion, and low LV volume, thereby providing an immediate
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increase in CO and improving the clinical condition of patients with HFpEF. The purpose of the
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initial in vitro study was to prove the concept that use of the LAAD can reduce LAP and increase
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CO while maintaining arterial pulsatility under diastolic heart failure (DHF) conditions when
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systolic function is preserved. For comparison, the same proof of concept device was evaluated
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as an LVAD (pumping from the LV to the aorta (Ao)) and also as a bypass from the LA to the
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aorta (LA-Ao).
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METHODS
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LAAD PERFORMANCE IN A MOCK CIRCULATORY LOOP
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We are currently developing a working prototype of the LAAD that can be implanted in
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the mitral position as shown in Figure 1; however, in this proof of concept study, we used an
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investigational, continuous-flow blood pump (proof of concept device) with specifications based
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on requirements for right ventricular support, as it has a suggested operational range suitable for
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mechanical support proposed in HFpEF. The LAAD is intended for intracardiac positioning in
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proximity to the atrio-ventricular groove. It will have a hybrid magnetic and hydrodynamic
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bearing and will be able to pump over a wide operating range to maintain optimal flow in
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support of cardiac output. The drive line will exit from the LA.
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The in vitro mock circulatory loop setup was comprised of a pneumatic mock ventricle (AB5000, ABIOMED Inc., Danvers, MA) that simulated the native LV, an adjustable arterial
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afterload and compliance, LA reservoir, and a continuous-flow, proof of concept device that is
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placed between the LA reservoir and the mock ventricle as the LAAD (Figure 2A). The pump
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flow is equal to CO and the total flow. To simulate blood, a mixture of water and glycerin
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(specific gravity, 1.060) was used as the working fluid.
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To simulate three different levels of DHF, the diastolic filling of the pneumatic ventricle
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was restricted by increasing the diastolic drive pressures of the pneumatic driver from -44 mm
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Hg at the normal heart condition to +15 mm Hg (DHF-1), +25 mm Hg (DHF-2), and +40 mm
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Hg (DHF-3). The systolic drive pressures of the pneumatic driver and the heart rate were kept
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constant during the entire study at 170 mm Hg and 80 bpm, respectively, with the systolic
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duration set to 250 msec. The compliance and resistance of the systemic circulation was
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adjusted to have an aortic pressure (AoP) of 120/80 mmHg under normal heart condition
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(systolic/diastolic = 170/-44 mm Hg), which generated a CO of approximately 4.0 L/min without
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activation of the LAAD.
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The LAAD was operated at three different speeds at each DHF condition: low (2,600
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rpm), middle (3,200 rpm), and high (3,800 rpm). When the LAAD was on, a tube was secured
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within the inflow valve housing of the AB5000 that was large enough to keep the inlet valve
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open (regurgitant) to simulate LAAD implantation at the mitral position (no mitral valve). When
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the data were taken without the LAAD, we used a normal competent inflow valve and a circuit to
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bypass the LAAD to avoid resistance of the pump when it was not active.
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LA-AO PERFORMANCE IN A MOCK CIRCULATORY LOOP The same mock loop that was used for LAAD evaluation was used to evaluate LA-AO performance; however, the outflow of the centrifugal pump was connected not to the LV but to
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the Ao, bypassing the LV (Figure 2B). A normal competent inflow valve was used. In this LA-
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Ao configuration, the total flow is the sum of the pump flow and CO. Similar to the LAAD
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study, the data were taken at normal heart conditions and three levels of DHF at three pump
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speeds, 2,800, 3,200, and 3,800 rpm.
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LVAD PERFORMANCE IN A MOCK CIRCULATORY LOOP The same mock loop as for the LAAD evaluation was used to evaluate LVAD
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performance; however, the inflow of the centrifugal pump was connected not to the LA reservoir
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but to an additional outlet of the pneumatic ventricle’s chamber that was created to simulate LV
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apex cannulation, similar to the clinical LVADs (Figure 2C). A normal competent inflow valve
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was used. In this LVAD configuration, the total flow is the sum of the pump flow and CO.
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Similarly to the LAAD study, the data were taken at normal heart condition and three levels of
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DHF, with pump speeds of 2,800, 3,200, and 3,800 rpm.
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DATA ACQUISITION AND ANALYSIS
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For each condition, we recorded pump flow and total flow (this is equal to CO in the
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LAAD configuration) using ultrasonic flow probes and flow meters (20XL, 10XL and T110,
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Transonic Systems, Inc., Ithaca, NY). Ultrasonic flow probes were clamped onto the ½ inch
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inner diameter pump outflow tubing and on the 1 inch inner diameter loop tubing between the
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compliance chamber and the reservoir. Pressures were monitored with fluid-filled lines
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connected at the LA reservoir and Ao.
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All data were recorded at 200 Hz using a PowerLab data acquisition system (ADInstruments Inc., Colorado Springs, CO), analyzed using LabChart (ADInstruments Inc.,
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Colorado Springs, CO), and then downloaded into Microsoft Excel (Microsoft Corp., Redmond,
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WA) to summarize and chart the test results.
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RESULTS
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LAAD CONFIGURATION
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With the LAAD pump off, CO decreased dramatically from 3.8 L/min with normal heart
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condition to 2.4, 2.0, and 1.2 L/min under DHF-1, DHF-2, and DHF-3, respectively (Figure 3A).
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With LAAD support, CO (or the total flow) recovered to a level slightly below that of the normal
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heart condition with the LAAD support at 3,200 rpm and surpassed that of normal heart
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condition at 3,800 rpm. It is interesting that the CO recovery was similar among the DHF-1,
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DHF-2, and DHF-3 conditions, although the CO without pump support was very different. At
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low pump speed (2,600 rpm) under normal heart condition, the CO decreased to 3.6 L/min from
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the 3.8 L/min that was observed with the pump off, which was due to the mitral regurgitation
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that was confirmed with the pump flow waveform.
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Similarly to CO, the mean AoP decreased dramatically from 100 mm Hg under normal
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heart condition to 59, 49, and 35 mmHg with DHF-1, DHF-2, and DHF-3, respectively, with the
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LAAD pump off (Figure 3B). With LAAD support, the AoP recovered to a level that almost
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reached that of the normal heart condition at 3,200 rpm and surpassed the normal heart condition
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(by 20 mm Hg) at 3,800 rpm. It is again interesting that the recovery of the AoP was very
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similar among DHF-1, DHF-2, and DHF-3, although the AoP values without pump support were
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very different.
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The mean LAP increased from 16.3 mm Hg for the normal heart condition to 21.6, 22.6,
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and 23.4 mm Hg for DHF-1, DHF-2, and DHF-3, respectively (Figure 3C). With LAAD
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support, the LAP recovered to a level that was similar to that of the normal heart condition at
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3,800 rpm. It is again interesting that the recovery of the LAP was very similar among DHF-1,
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DHF-2, and DHF-3, although the LAP values without pump support were very different.
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COMPARISON OF LAAD DATA WITH THE LA-AO CONFIGURATION AND THE LVAD
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CONFIGURATION
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Figure 4 compares the results of the LAAD configuration with those of the LA-Ao and
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LVAD configurations at a pump speed of 3,200 rpm. The total flow was similar between the
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LAAD and LA-Ao configurations but was lower with the LVAD configuration under DHF
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conditions (Figure 4A) due to the fact that the volume in the LV was limited, as in to the clinical
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situation for DHF. The mean AoP followed a similar trend to the total flow (Figure 4B). The
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mean LAP was higher under the LA-Ao and LVAD configurations compared with that with the
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LAAD under DHF conditions (Figure 4C).
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Figure 5 compares the results of the LAAD with those of the LA-Ao configuration in
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more detail at three different pump speeds. The total flow increased as the pump speed increased
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very similarly in the LAAD and LA-Ao configurations (Figure 5A). The results of mean AoP
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reflected those of the total flow (Figure 5B). A large difference was observed in the arterial
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pulse pressure (Figure 5C). Whereas the arterial pulse pressure was maintained with the LAAD
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configuration, it decreased as the pump speed increased with the LA-Ao configuration. This low
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pulsatility is a limitation of the LA-Ao configuration and is also a concern for potential
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thromboembolisms due to blood stagnation in the LV.8 With the LAAD, the entire flow goes
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from the LV through the aortic valve to keep the valve fully in action, while the aortic valve is
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always closed in the LA-Ao configuration, which may cause a fusion of the aortic valve cusps,
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aortic valve regurgitation, and/or thrombus in the aortic root due to blood stagnation.
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Discussion These results demonstrated that the LAAD increased CO and AoP and decreased LAP
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under DHF conditions while maintaining arterial pulsatility and full function of the aortic valve.
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Despite the multifactorial origin of HFpEF, patient conditions can be improved by addressing
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LV filling, which is the mechanism of action for this proposed new device solution. In these
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patients, the LV cavity is small due to thickened and stiffened LV muscle (impaired compliance)
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(Figure 1). The LA is typically dilated, and LAP is elevated, because it requires much force
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(pressure) for the LA to pump blood to the stiffened LV. This physiology is similar to that of
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mitral stenosis, but the LV cavity, instead of the mitral valve, is the stenotic object. Therefore,
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we believe a typical HFpEF candidate would be a suitable recipient for the LAAD. Dilatation of
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the LV cavity and increase in LV compliance are the primary therapy for this physiology but are
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very difficult to achieve.
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Drawing blood from the LA and pumping it into the aorta has been considered;9 however,
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thromboembolism would be an issue in this configuration due to blood stagnation in the LV, and
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LV remodeling would be unlikely to occur. We evaluated this configuration and demonstrated
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reduced pulsatility with higher pump speeds (Figure 5C), which could be another limitation of
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this pump placement. LVADs have been successfully used for patients with HFrEF;10 however,
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patients with hypertrophic cardiomyopathy or restrictive cardiomyopathy are generally excluded
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from LVAD therapy because of the reduced LV end-diastolic dimensions seen in these patients11
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and perceived risk of suction with continuous-flow LVADs. In this study, we demonstrated that
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an LVAD did not support DHF patients well due to small LV volume (Figure 4).
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Another possible treatment for HFpEF patients is to place a shunt between the left and
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right atria to reduce LAP and LV end-diastolic pressure.12 However, pulmonary capillary wedge
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pressure, a surrogate for LA pressure, was reduced by only 2 mm Hg (from 19 ± 6 mm Hg to 17
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± 6 mm Hg) at 12 months after interatrial shunt device implantation, and there was no reduction
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in the mean pulmonary arterial pressure (from 25 ± 8 mm Hg to 26 ± 8 mm Hg). Furthermore,
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this method is not likely to increase CO or promote LV remodeling.
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The LAAD can be operated at a constant pump speed as well as with pump speed
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modulation (co-pulsation, counterpulsation, or asynchronous mode). In constant speed mode,
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the pump flow is higher during diastole due to a low pressure difference (LVP – LAP) and lower
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during systole due to a higher pressure difference. Importantly, all flow paths created by the
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LAAD follow natural (anatomical and physiological) patterns.
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STUDY LIMITATIONS
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There are limitations to this study. One of the concerns regarding LAAD support is an
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increase in the LV pressure during diastole that may affect coronary flows. In this mock loop
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with a pneumatic ventricle, the LV pressure during diastole showed very flat pressures (not
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shown) equal to the diastolic pneumatic driving pressures at each condition (normal heart (-44
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mm Hg), DHF-1 (+15 mm Hg), DHF-2 (+25 mm Hg), and DHF-3 (+40 mm Hg)) until the
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diaphragm contacted the housing (full filling). This is because these two chambers (LV fluid
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chamber and pneumatic chamber) are separated only by a thin diaphragm. In addition, there is
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no additional increase in LV volume once the diaphragm contacts the housing. Furthermore, the
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diastolic drive pressure of the pneumatic ventricle was constant during each of the three different
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degrees of diastolic dysfunction and therefore does not adequately simulate dynamic LV
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diastolic dysfunction. We need an animal study to see the effects of potential elevation of the
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LV end-diastolic pressure on coronary blood flow and also to evaluate right ventricular function
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due to ventricular interdependence. Another limitation is that the LAP at the normal heart
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condition without LAAD was higher (16.3 mm Hg) than the expected physiologic range and
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increased only moderately while there were marked decreases in CO and mean AoP under DHF
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conditions, which are not typically seen in HFpEF patients. HFpEF has many phenotypes and
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co-morbidities hence the applicability of this new device broadly versus a more narrow patient
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population must be determined. We believe that the relative change in LAP will not be affected
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by this relatively high value. Finally, our model did not include a simulation of the LA
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contractility, which may play an important role in the LAAD configuration.
279 280
CONCLUSIONS
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These initial in vitro study results support our hypothesis that use of the LAAD increases
282
CO and AoP and decreases LAP under DHF conditions while maintaining arterial pulsatility and
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full function of the aortic valve. Our model simulates the human physiology of HFpEF. If the
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animal model proves feasible the potential for effective hemodynamic treatment in humans with
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disease will be significant.
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References
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1.
Go AS, Mozaffarian D, Roger VL, et al. American Heart Association Statistics
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Committee, and Stroke Statistics Subcommittee. Executive summary: heart disease and
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stroke statistics--2014 update: a report from the American Heart Association. Circulation.
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2014;129:399-410. PMCID: PMC2891613.
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failure: public and private health burden. Eur Heart J. 1998;19 Suppl P:P9-16. 3.
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McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart
Braunwald E. Research advances in heart failure: a compendium. Circ Res. 2013;113:633-645.
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Heidenreich PA, Albert NM, Allen LA, et al. American Heart Association Advocacy
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Coordinating Committee, Council on Arteriosclerosis Thrombosis, Vascular Biology,
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Council on Cardiovascular Radiology, Intervention, Council on Clinical Cardiology,
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Council on Epidemiology and Prevention; troke Council. Forecasting the impact of heart
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failure in the United States: a policy statement from the American Heart Association.
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Circ Heart Fail. 2013;6:606-619. PMCID: PMC3908895.
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Tanai E, Frantz S. Pathophysiology of Heart Failure. Compr Physiol. 2015;6:187-214.
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Misbah R, Fukamachi K. Heart failure with preserved ejection fraction: A review for the
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clinician. J Cardiol Cardiovasc Ther (in press). 7.
Xanthopoulos A, Triposkiadis F, Starling RC. Heart failure with preserved ejection
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fraction: Classification based upon phenotype is essential for diagnosis and treatment.
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Trends Cardiovasc Med. 2018;28:392-400.
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8.
Reilly MP, Wiegers SE, Cucchiara AJ, et al. Frequency, risk factors, and clinical
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outcomes of left ventricular assist device-associated ventricular thrombus. Am J Cardiol.
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2000;86:1156-1159, A1110.
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Burkhoff D, Maurer MS, Joseph SM, et al. Left atrial decompression pump for severe
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heart failure with preserved ejection fraction: theoretical and clinical considerations.
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JACC Heart Fail. 2015;3:275-282.
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Levitated Cardiac Pump in Heart Failure. N Engl J Med. 2018;378:1386-1395. 11.
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Mehra MR, Goldstein DJ, Uriel N, et al. Two-Year Outcomes with a Magnetically
Lund LH, Matthews J, Aaronson K. Patient selection for left ventricular assist devices. Eur J Heart Fail. 2010;12:434-443.
12.
Kaye DM, Hasenfuss G, Neuzil P, et al. One-Year Outcomes After Transcatheter
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Insertion of an Interatrial Shunt Device for the Management of Heart Failure With
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Preserved Ejection Fraction. Circ Heart Fail. 2016;9.
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Figure Legends
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Figure 1. Schematic drawing of the Left Atrial Assist Device (LAAD) concept. A: A dilated
326
left atrium (LA), thick left ventricular (LV) wall, and small LV cavity in heart failure
327
with preserved ejection fraction (HFpEF) are shown. B: The LAAD is implanted in
328
the mitral position to replace the mitral valve of a HFpEF patient to pump blood from
329
the LA to properly fill the LV.
330
Figure 2. Schematic drawing of the three pump configurations. A: For the Left Atrial Assist
331
Device (LAAD) configuration, the pump is placed between the left atrial chamber
332
and the pneumatic ventricle. In this configuration, pump flow is equal to cardiac
333
output and the total flow. B: For the left atrium-to-aorta (LA-Ao) configuration, the
334
pump is placed between the left atrial chamber and the aorta, bypassing the pneumatic
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ventricle. In this configuration, the total flow is the sum of the pump flow and the
336
cardiac output. C: For the left ventricular assist device (LVAD) configuration, the
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pump is placed between the pneumatic ventricle and the aorta, similar to a clinical
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LVAD. In this configuration, the total flow is the sum of the pump flow and cardiac
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output. AoP – aortic pressure; LAP – left atrial pressure.
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Figure 3. Cardiac output, mean aortic pressure (AoP), and mean left atrial pressure (LAP) vs.
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Left Atrial Assist Device (LAAD) pump speed (or off) under normal heart condition
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and three levels of diastolic heart failure (DHF) conditions. A: With the LAAD pump
343
off, cardiac output decreased dramatically as DHF progressed. With LAAD support,
344
cardiac output recovered to almost that of the normal heart condition with LAAD
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support at 3,200 rpm and surpassed that of the normal heart condition at 3,800 rpm
346
under all three levels of DHF. B: Mean AoP results were similar to those of cardiac
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output. C: With the LAAD off, the mean LAP increased as DHF progressed. With
348
LAAD support, the mean LAP almost reached that of the normal heart condition at
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3,800 rpm.
350
Figure 4. Total flow, mean aortic pressure (AoP), and mean left atrial pressure (LAP) for three
351
different configurations at a pump speed of 3,200 rpm. A: The total flow was similar
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between the Left Atrial Assist Device (LAAD) and left atrium-to-aorta (LA-Ao)
353
configuration but was lower for the left ventricular assist device (LVAD)
354
configuration under diastolic heart failure (DHF) conditions. B: The mean AoP
355
followed a trend similar to that of the total flow. C: The mean LAP was higher for
356
the LA-Ao and LVAD configurations compared with the LAP for the LAAD under
357
DHF conditions.
358
Figure 5. Total flow, mean aortic pressure (AoP), and arterial pulse pressure for the Left Atrial
359
Assist Device (LAAD) and left atrium-to-aorta (LA-Ao) configuration at three
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different pump speeds and the two most severe diastolic heart failure (DHF)
361
conditions. A: The total flow increased as the pump speed increased in both the
362
LAAD and LA-Ao configurations. B: Mean AoP showed a trend similar to that of
363
the total flow. C: Whereas the arterial pulse pressure was maintained with the LAAD
364
configuration, it decreased as the pump speed increased for the LA-Ao configuration.
365
Central Picture. Schematic drawing of the LAAD implanted in the mitral position of a HFpEF
366 367
patient.