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Cardiology Articles Cardiology/Cardiovascular Research

9-27-2022

Five-Year Outcomes in Patients With Fully Magnetically Levitated

vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3
Randomized Trial
Mandeep R. Mehra

Daniel J. Goldstein

Joseph C. Cleveland

Jennifer A. Cowger
Henry Ford Health, jcowger1@hfhs.org

Shelley Hall

See next page for additional authors

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Recommended Citation
Mehra MR, Goldstein DJ, Cleveland JC, Cowger JA, Hall S, Salerno CT, Naka Y, Horstmanshof D, Chuang J,
Wang A, and Uriel N. Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left
Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial. Jama 2022; 328(12):1233-1242.

This Article is brought to you for free and open access by the Cardiology/Cardiovascular Research at Henry Ford
Health Scholarly Commons. It has been accepted for inclusion in Cardiology Articles by an authorized
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Authors
Mandeep R. Mehra, Daniel J. Goldstein, Joseph C. Cleveland, Jennifer A. Cowger, Shelley Hall, Christopher
T. Salerno, Yoshifumi Naka, Douglas Horstmanshof, Joyce Chuang, AiJia Wang, and Nir Uriel

This article is available at Henry Ford Health Scholarly Commons: https://scholarlycommons.henryford.com/

cardiology_articles/976
 Research

JAMA | Original Investigation

Five-Year Outcomes in Patients With Fully Magnetically Levitated

vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3
Randomized Trial
Mandeep R. Mehra, MD, MSc; Daniel J. Goldstein, MD; Joseph C. Cleveland, MD; Jennifer A. Cowger, MD, MS;
Shelley Hall, MD; Christopher T. Salerno, MD; Yoshifumi Naka, MD, PhD; Douglas Horstmanshof, MD;
Joyce Chuang, PhD; AiJia Wang, MPH; Nir Uriel, MD, MSc

Visual Abstract
IMPORTANCE Although durable left ventricular assist device (LVAD) therapy has emerged as Supplemental content
an important treatment option for patients with advanced heart failure refractory to
pharmacological support, outcomes, including survival, beyond 2 years remain
poorly characterized.

OBJECTIVE To report the composite end point of survival to transplant, recovery, or LVAD
support free of debilitating stroke (Modified Rankin Scale score >3) or reoperation to replace
the pump 5 years after the implant in participants who received the fully magnetically
levitated centrifugal-flow HeartMate 3 or axial-flow HeartMate II LVAD in the MOMENTUM 3
randomized trial and were still receiving LVAD therapy at the 2-year follow-up.

DESIGN, SETTING, AND PARTICIPANTS This observational study was a 5-year follow-up of the
MOMENTUM 3 trial, conducted in 69 US centers, that demonstrated superiority of the
centrifugal-flow LVAD to the axial-flow pump with respect to survival to transplant, recovery,
or LVAD support free of debilitating stroke or reoperation to replace the pump at 2 years.
A total of 295 patients were enrolled between June 2019 to April 2021 in the extended-phase
study, with 5-year follow-up completed in September 2021.

EXPOSURES Of 1020 patients in the investigational device exemption per-protocol

population, 536 were still receiving LVAD support at 2 years, of whom 289 received the
centrifugal-flow pump and 247 received the axial-flow pump.

MAIN OUTCOMES AND MEASURES There were 10 end points evaluated at 5 years in the
per-protocol population, including a composite of survival to transplant, recovery, or LVAD
support free of debilitating stroke or reoperation to replace the pump between the
centrifugal-flow and axial-flow pump groups and overall survival between the 2 groups.

RESULTS A total of 477 patients (295 enrolled and 182 provided limited data) of 536 patients
still receiving LVAD support at 2 years contributed to the extended-phase analysis
(median age, 62 y; 86 [18%] women). The 5-year Kaplan-Meier estimate of survival to
transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the
pump in the centrifugal-flow vs axial-flow group was 54.0% vs 29.7% (hazard ratio, 0.55
[95% CI, 0.45-0.67]; P < .001). Overall Kaplan-Meier survival was 58.4% in the
centrifugal-flow group vs 43.7% in the axial-flow group (hazard ratio, 0.72 [95% CI,
0.58-0.89]; P = .003). Serious adverse events of stroke, bleeding, and pump thrombosis
were less frequent in the centrifugal-flow pump group.

CONCLUSIONS AND RELEVANCE In this observational follow-up study of patients from the
MOMENTUM 3 randomized trial, per-protocol analyses found that receipt of a fully
magnetically levitated centrifugal-flow LVAD vs axial-flow LVAD was associated with a better
composite outcome and higher likelihood of overall survival at 5 years. These findings
support the use of the fully magnetically levitated LVAD. Author Affiliations: Author
affiliations are listed at the end of this
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02224755 and NCT03982979
article.
Corresponding Author: Mandeep R.
Mehra, MD, MSc, Center for
Advanced Heart Disease, Brigham
and Women’s Hospital, Harvard
Medical School, 75 Francis St, Boston,
JAMA. 2022;328(12):1233-1242. doi:10.1001/jama.2022.16197 MA 02115 (mmehra@bwh.harvard.
Published online September 8, 2022. edu).

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 Research Original Investigation Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices
D
espite benefits of pharmacological therapy for chronic
heart failure, some patients exhibit refractoriness to
therapy. Patients with refractory heart failure have
worse quality of life, inability to tolerate drug therapy, and poor
prognosis.1,2 Advanced heart failure may be fatal without use
of a left ventricular assist device (LVAD), cardiac transplant,
or palliative inotropic support. Among available LVADs, the cen-
trifugal-flow HeartMate 3 has been engineered with wide blood
flow pathways, friction-free movement using fully magneti-
cally levitated technology, and intrinsic pulsatility to reduce
shear stress and stasis of blood, while the Heartmate II is a con-
tinuous axial-flow pump that requires thoracoabdominal place-
ment. Although LVAD therapy has gained support, clinical out-
comes and life prolongation beyond 2 years remain poorly
characterized.3 As a consequence, referrals for LVAD implan-
tation may occur late and with worse end-organ function.
The Multicenter Study of MagLev Technology in Patients
Undergoing Mechanical Circulatory Support Therapy With
HeartMate 3 (MOMENTUM 3) randomized clinical trial dem-
onstrated that the fully magnetically levitated centrifugal-
flow LVAD, compared with the axial-flow pump, resulted in bet-
ter outcomes driven by greater hemocompatibility 2 years after
the implant.4 However, the overall survival difference be-
tween the treatment group at 2 years did not reach statistical
significance (hazard ratio [HR], 0.88 [95% CI, 0.67-1.16]).4 The
US Food and Drug Administration approved the centrifugal-
flow pump for lifelong use (destination therapy) in advanced
heart failure in 2018, conditional on an extended evaluation
to 5 years of follow-up among those still receiving LVAD sup-
port in the trial.
The purpose of this study was to report the composite end
point of survival to transplant, recovery, or LVAD support free
of debilitating stroke (Modified Rankin Scale score >3) or re-
operation to replace the pump 5 years after the implant in par-
ticipants who received the centrifugal-flow pump or axial-
flow pump in the investigational device exemption (IDE) trial
and were still receiving LVAD support at the 2-year follow-up.
Methods
Study Design
The IDE trial was designed to compare the safety and effec-
tiveness of the centrifugal-flow pump with the axial-flow pump
in patients with advanced heart failure who were refractory
to pharmacological support through 2 years after the implant
and was conducted at 69 centers in the US (NCT02224755).
Both LVADs are manufactured by Abbott. Patients were
included irrespective of the intended goal of therapy of either
bridge to transplant or destination therapy. As shown in
Figure 1, patients were randomized to the centrifugal-flow
pump or axial-flow pump group (intent-to-treat population).
Between September 2014 and August 2016, a total of 515
patients in the centrifugal-flow pump group and 505 in the
axial-flow pump group underwent implantation of their
assigned study device (per-protocol population). The trial was
originally designed to conclude after 2 years of follow-up, which
occurred in 2018. There were 536 patients (289 in the
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Key Points
Question In patients with advanced heart failure, what is the
difference in the composite end point of survival to transplant,
recovery, or left ventricular assist device (LVAD) support free of
debilitating stroke or reoperation to replace the pump 5 years
following implantation of a fully magnetically levitated
centrifugal-flow vs axial-flow LVAD?
Findings This observational 5-year follow-up study included 477
of 536 surviving patients from the MOMENTUM 3 randomized trial
at 2 years. In a per-protocol analysis of patients receiving a fully
magnetically levitated vs axial-flow LVAD, the composite outcome
occurred in 54.0% vs 29.7% of patients (hazard ratio, 0.55) and
overall survival in 58.4% vs 43.7% of patients (hazard ratio, 0.72).
Results of both comparisons were statistically significant.
Meaning Among patients with advanced heart failure, receipt of a
fully magnetically levitated centrifugal-flow LVAD vs axial-flow
LVAD was associated with a better composite outcome and higher
likelihood of overall survival at 5 years.
centrifugal-flow pump group and 247 in the axial-flow pump
group) still receiving LVAD support at the completion of the
2-year follow-up in the pivotal trial. The original trial design,
results, and trial protocol have been previously published.4,5
The US Food and Drug Administration approval for the cen-
trifugal-flow pump long-term indication was granted in
October 2018. As a condition of approval, an observational ex-
tended follow-up study of patients still receiving LVAD sup-
port in the pivotal trial from 2 to 5 years after the implant was
mandated. This postapproval extended-phase study was con-
ducted under a unique protocol.
The protocol for the postapproval extended-phase study
was separate from that prepared for the original trial and re-
quired participating centers to complete the start-up process
as a de-novo study, obtain institutional review board ap-
proval, and obtain consent from all patients still receiving LVAD
therapy beyond 2 years (Supplement 1). The study was con-
ducted at the same sites that participated in the pivotal (IDE)
trial. Centers determined their patients’ eligibility for the ex-
tended-phase protocol based on medical records at the site.
If a patient died before providing consent (and after 2-year
follow-up), centers could provide the date and cause of death
as part of institutional review board approval. Patients receiv-
ing LVAD support who provided consent to the extended-
phase follow-up were followed up until 5 years after the im-
plant or a prespecified outcome (death, transplant, explant/
permanent deactivation, or withdrawal), whichever occurred
first. Patients who underwent a device exchange to a pump
other than their study-assigned LVAD were withdrawn. Data
were collected from study visits performed at 3, 4, and 5 years
after the implant. In addition, there were some centers that de-
clined to participate in the extended-phase study protocol;
however, institutional review board approval was obtained for
the centers to provide limited outcome data within 5 years af-
ter the implant for their patients (death, transplant, explant,
still receiving LVAD therapy at 5 years, and outcome dates).
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 Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices Original Investigation Research

Figure 1. Flow of Patients in a Trial of 5-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices

2744 Adults with advanced heart failure

screened for inclusion

1716 Excludeda
761 Met exclusion criteria
214 Insurance denials
198 Did not consent
142 Did not meet inclusion criteria
68 Not LVAD candidate
333 Other or multiple reasons

1028 Randomizedb

516 Randomized to centrifugal- 512 Randomized to axial-flow

flow pump group pump group

1 Withdrawn before implant because of death 7 Withdrawn before implant

2 Died
2 Did not undergo LVAD implant
1 Withdrew consent
1 Received transplant
1 Implanted with nonstudy LVAD

515 Underwent pump implant 505 Underwent pump implant

226 Experienced outcome before 2 y 258 Experienced outcome before 2 y

119 Received transplant 137 Received transplant
98 Died 103 Died
6 Withdrawn 15 Withdrawn
3 Change in patient statusc 2 Change in patient statusc
2 Switch to non–study assigned device 11 Switched to non–study assigned device
1 Withdrew consent 1 Withdrew consent
3 Pump removed or permanently deactivated 1 Transferred care to non–study site
3 Pump removed or permanently deactivated

289 Completed 2-y follow-up 247 Completed 2-y follow-up

31 Withdrawn with no available data beyond 2 y 28 Withdrawn with no available data beyond 2 y
14 Unable to be reached or to provide consent 7 Unable to be reached or provide consent for
for extended follow-up extended follow-up
12 Site declined providing extended follow-up data 14 Site declined providing extended follow-up data
5 Transferred care to non–study site 5 Transferred care to non–study site
2 Receiving palliative/hospice care

258 With data beyond 2 y contributed 219 With data beyond 2 y contributed
to extended-phase analysisd to extended-phase analysisd

117 Experienced outcome before 5 y 134 Experienced outcome before 5 y

58 Died 81 Died
37 Received transplant 29 Received transplant
21 Withdrawn 22 Withdrawn
17 Did not provide consent for extended 15 Did not provide consent for extended
follow-up follow-up
2 Lost to follow-up 7 Switched to non–study assigned device
1 Transferred care to non–study site 2 Pump removed or permanently deactivated
1 Withdrew consent
1 Pump removed or permanently deactivated

141 Completed 5-y follow-up 85 Completed 5-y follow-up

d
The investigational device exemption trial followed up patients for 2 years and A total of 178 patients with magnetically levitated centrifugal-flow pumps and 117
the postapproval extended-phase study followed up patients still receiving left with axial-flow pumps were consented then enrolled in the extended-phase
ventricular assist device (LVAD) therapy up to 5 years. study protocol. Limited 5-year outcome data were obtained in 63 patients in the
a
Specific inclusion and exclusion criteria were not documented at screening. centrifugal-flow pump group and 87 in the axial-flow pump group who were not
b
successfully enrolled in the extended-phase study. There were 17 patients in the
Patients were randomized in a 1:1 ratio and randomization was stratified by
centrifugal-flow pump group and 15 in the axial-flow pump group who did not
study center and blocked to maintain the 1:1 ratio over time.
provide consent for extended follow-up and were considered to be alive on the
c
Incarceration, nonadherence, suicide attempt/depression, or cancer diagnosis. date of refusal and then censored in the analysis.

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 Research Original Investigation Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices
End Points
There were 10 end points assessed in the per-protocol popu-
lation. The composite end point was survival to transplant, re-
covery, or LVAD support free of debilitating stroke (Modified
Rankin Scale score >3) or reoperation to replace the pump 5
years after the implant. Other end points included patient out-
comes (transplant, explant/permanent deactivation, or with-
drawal) and survival and frequency and incidence of serious
adverse events (bleeding [including gastrointestinal bleed-
ing], major infection, hemolysis, device thrombosis and de-
vice malfunction, and neurological dysfunction [including
stroke]). Functional status as assessed by New York Heart
Association (NYHA) class and 6-minute walk distance (6MWD)
was also evaluated.
Study Conduct and Analysis Plan Modifications
Due to the gap created by ending the pivotal trial and starting
the extended-phase study, data beyond 2 years could not be
collected in some patients (eg, their site declined to provide
any extended follow-up data, they were unable to be reached
to complete consent, they transferred care to a nonparticipat-
ing center) (Figure 1). A total of 295 patients were success-
fully consented and enrolled under the extended-phase study
protocol from June 2019 to April 2021 (eTable 1 in Supple-
ment 2), and adverse events and functional status assess-
ments could be collected only in these patients. The final 5-year
follow-up visit was completed in September 2021. During the
study follow-up, the COVID-19 pandemic created difficulties
with obtaining NYHA class and 6MWD. Details regarding study
conduct are provided in Supplement 1.
The operational challenges of the extended-phase study re-
duced the investigators’ ability to assess the original intended
primary end point of the study with completeness, which was
a composite requiring data on the serious adverse event of
stroke. Due to the limitations imposed by missing data, the trial
publication and presentation committee determined that over-
all survival should serve as the modified principal study end
point because it was least influenced by the operational chal-
lenges and offered the most completeness in data collection. Ad-
ditional post hoc end points were specified, including an analy-
sis in patients who received an LVAD for destination therapy
intent and cause-specific mortality with deaths categorized into
those due to hemocompatibility-related events (stroke, bleed-
ing, and device thrombosis), heart failure (including right ven-
tricular failure), infection, and all other causes. All deaths oc-
curring during the 2-year follow-up of the pivotal trial were
adjudicated by a clinical events committee (98 deaths in the cen-
trifugal-flow pump group and 103 in the axial-flow pump group).
Deaths in patients who successfully consented for extended fol-
low-up were also adjudicated by the clinical events committee
(7 in the centrifugal-flow pump group and 9 in the axial-flow
pump group). Subgroup analyses were performed for catego-
ries based on age, sex, race and ethnicity, intended goal of
therapy (bridge to transplant or destination therapy), and se-
verity of illness (based on Interagency Registry for Mechani-
cally Assisted Circulatory Support [INTERMACS] profile) at
baseline). Race and ethnicity were collected in the trial to in-
form on the treatment effect across different subgroups and were
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self-reported based on predefined categories of Asian, Black,
Native Hawaiian or Pacific Islander, and White race and an open
category for all other.
Statistical Methods
Continuous variables are presented as mean (SD) or median (IQR)
and categorical variables as counts and percentages. The sample
size for the extended phase included patients from the IDE trial
still receiving LVAD support at 2 years who then contributed any
data beyond 2 years for at least 1 end point analysis.
The composite end point of survival to transplant, recov-
ery, or LVAD support free of debilitating stroke or reoperation
to replace the pump was evaluated with the Kaplan-Meier
method and Cox proportional hazards modeling. Propor-
tional hazards assumptions were confirmed by creating and
testing the significance of time-dependent covariates. Events
constituting failure of the composite end point included death,
debilitating stroke, and reoperation. Withdrawals were also
considered failure events; however, in the extended phase this
only applied to patients who were successfully consented for
extended follow-up. Serious adverse events during the ex-
tended phase were not collected in all patients contributing
to the analysis cohort, and it was assumed that these patients
had no debilitating stroke after 2 years.
Survival rates were estimated with the Kaplan-Meier
method and HRs with 95% CIs were calculated with Cox pro-
portional hazards modeling. Patients who underwent heart
transplant, device removal/deactivation, or withdrawal were
censored at the time of the outcome. The Fine-Gray model was
used to evaluate mortality risk while accounting for the com-
peting risk of heart transplant and to evaluate cause-specific
mortality as a post hoc analysis. To assess the treatment ef-
fect on survival across different subgroups (based on age, sex,
race and ethnicity, intended goal of therapy, and INTERMACS
profile at baseline), an interaction term between the sub-
group covariate and the treatment group was included in the
Cox proportional hazards models.
Because outcome data in the extended-phase study were
not able to be collected in all patients who were receiving LVAD
support at 2 years, the robustness of the observed survival rates
in the extended-phase study was evaluated in a post hoc analy-
sis. Missing outcome data from the extended-phase study were
filled in with additional data (occurrence of death, trans-
plant, device explant, including dates of these outcomes,
within 5 years after implant) from the sponsor’s device track-
ing database as permissible by state regulations. No data from
patients refusing consent for the extended-phase study were
used. A tipping point analysis using δ-adjusted bootstrap-
based multiple imputation was implemented to test the as-
sumption of noninformative censoring for the patients re-
maining withdrawn after inclusion of the supplemental device
tracking data, excluding those undergoing exchange to a non–
study-assigned device. Thirty rounds of imputation were per-
formed and the δ for centrifugal-flow pump was increased by
1 unit each time until the treatment effect in favor of centrifu-
gal-flow pump was no longer significant. In the axial-flow
pump group, the mortality hazard was assumed to be the same
between withdrawn vs patients who were not withdrawn.
jama.com
 Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices Original Investigation Research

Rates for serious adverse events occurring from 0 to 5 years

Table. Baseline Characteristics in a Study of 5-Year Outcomes
are presented in events per patient-year and compared be- in Patients With Fully Magnetically Levitated vs Axial-Flow
tween treatment groups with rate ratios and 95% CIs calcu- Left Ventricular Assist Devices
lated using Poisson regression. Only patients who consented
No. (%)
for extended follow-up contributed serious adverse events af-
Magnetically levitated
ter 2 years (178 in the centrifugal-flow pump group and 117 in centrifugal-flow pump Axial-flow pump
the axial-flow pump group). Characteristic (n = 515) (n = 505)
Age, median (IQR), y 62 (52-68) 63 (54-69)
Two-sided P values <.05 were considered significant. Be-
cause of the potential for type I error due to multiple compari- Men 410 (79.6) 413 (81.8)

sons, findings for analyses of secondary end points should be Women 105 (20.4) 92 (18.2)
interpreted as exploratory. All statistical analyses were per- Race and ethnicitya
formed with SAS, version 9.4 (SAS Institute). Asian 8 (1.6) 3 (0.6)
Black 145 (28.2) 119 (23.6)
Otherb 21 (4.1) 17 (3.4)
Native Hawaiian 0 4 (0.8)
Results or Pacific Islander
White 341 (66.2) 362 (71.7)
Patient Population
In the IDE trial’s per-protocol population of 1020 patients, 515 Hispanic ethnicity 28 (5.4) [n = 514] 27 (5.3)

patients received the centrifugal-flow LVAD and 505 patients Body surface area, 2.07 (0.27) 2.08 (0.28)
mean (SD), m2
received the axial-flow LVAD (Figure 1). A total of 289 pa-
BMI, median (IQR) 28.4 (24.6-33.0) 27.9 (24.2-32.1)
tients in the centrifugal-flow pump group and 247 in the axial-
Ischemic cause 216 (41.9) 236 (46.7)
flow pump group were still receiving LVAD support at 2 years. of heart failure
Due to the gap created by ending the pivotal trial and starting Medical history
the extended-phase study, there were 59 patients for whom Diabetes 233 (45.2) 221 (43.8)
no data beyond 2 years were able to be collected. The remain- Atrial fibrillation 215 (41.7) 235 (46.5)
ing 477 patients had data beyond 2 years available and con- Coronary artery bypass 102 (19.8) 111 (22.0)
stitute the sample size for the extended phase. Of these pa- Stroke 50 (9.7) 56 (11.1)
tients, 295 patients were successfully consented and enrolled
Valve replacement/repair 36 (7.0) 30 (5.9)
under the extended-phase study protocol. In the remaining 182
Cardiac function
patients, limited 5-year outcome data were obtained in 150 pa- and pressures,
tients and 32 patients who did not provide consent for ex- median (IQR)c

tended follow-up were considered to be alive on the date of Mean arterial pressure, 80.1 (10.8) 78.9 (10.0)
mm Hg [n = 503]
refusal and then censored, and no additional data were re- Pulmonary-capillary 23 (17-29) 23 (17-29)
trieved from these patients. wedge pressure, [n = 503] [n = 495]
mm Hg
The baseline characteristics for the treatment group in the
Cardiac index, 1.90 (1.60-2.24) 1.89 (1.60-2.20)
per-protocol population are shown in the Table and are largely L/min/m2 [n = 511] [n = 503]
similar between the groups. There were more Black patients Pulmonary vascular 2.84 (1.90-4.10) 2.74 (1.90-3.88)
and fewer White patients in the centrifugal-flow pump group resistance, Wood units [n = 498] [n = 493]
compared with the axial-flow pump group. Baseline demo- Right atrial pressure, 10 (6-15) 9 (5-15)
mm Hg [n = 504] [n = 495]
graphics were also similar between treatment groups in the des-
Laboratory values,
tination therapy population. Patients in the centrifugal-flow median (IQR)d
pump group had a higher pulmonary vascular resistance and Serum sodium, 136 (133-138) 136 (133-138)
mmol/L
more mitral regurgitation of any severity compared with pa-
Serum creatinine, 1.29 (1.01-1.61) 1.30 (1.06-1.60)
tients in the axial-flow pump group, but they were less likely mg/dL
to be receiving diuretics (eTable 2 in Supplement 2). Demo- Estimated glomerular 58 (43-75) 56 (43-72)
graphic information is also prov ided in eTable 3 in filtration rate,
mL/min/1.73 m2
Supplement 2 for the 477 patients who constitute the sample
Intended use of device
size for the extended phase.
Destination therapy 317 (61.6) 307 (60.8)
Bridge to transplant 112 (21.7) 120 (23.8)
Composite End Point
Bridge to candidacy 86 (16.7) 78 (15.4)
The composite of 5-year survival to transplant, recovery, or for transplant
LVAD support free of debilitating stroke or reoperation to re- INTERMACS profilee n = 514 n = 501
place the pump occurred in 336 of 515 patients (65.2%) in the 1-2 167 (32.5) 159 (31.7)
centrifugal-flow group vs 240 of 505 (47.5%) in the axial-flow
3 272 (52.9) 251 (50.1)
group. The Kaplan-Meier estimates of event-free survival at 5
4-7 75 (14.6) 91 (18.2)
years were 54.0% in the centrifugal-flow group vs 29.7% in the
axial-flow group (HR, 0.55 [95% CI, 0.45-0.67]; P < .001) (continued)

(Figure 2A). The first event type leading to failure of the

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 Research Original Investigation Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices

in the centrifugal-flow pump group compared with 39.4% in

Table. Baseline Characteristics in a Study of 5-Year Outcomes
in Patients With Fully Magnetically Levitated vs Axial-Flow the axial-flow pump group (HR, 0.70 [95% CI, 0.55-0.90];
Left Ventricular Assist Devices (continued) P = .005) (eFigure 1 in Supplement 2). Censoring of patients
who refused consent for extended follow-up at 2 years in-
No. (%)
stead of the date of refusal did not significantly change the
Magnetically levitated
centrifugal-flow pump Axial-flow pump 5-year survival rates.
Characteristic (n = 515) (n = 505)
Valvular insufficiencyf n = 513
Serious Adverse Events
Aortic 152 (29.6) 147 (29.1) Serious adverse event rates from 0 to 5 years are pre-
Moderate or severe 11 (2.1) 7 (1.4) sented in Figure 3 and eTable 5 in Supplement 2. Rates for
Mitral 464 (90.4) 439 (86.9) hemocompatibility-related adverse events were signifi-
Moderate or severe 216 (42.1) 228 (45.1) cantly lower in the centrifugal-flow group compared with
Tricuspid 431 (84.0) 419 (83.0) the axial-flow pump group (device thrombosis: 0.010 vs
Moderate or severe 158 (30.8) 127 (25.1) 0.108 events/patient-years; stroke: 0.050 vs 0.136 events/
Concomitant medications patient-years; bleeding: 0.430 vs 0.765 events/patient-
Inotrope 444 (86.2) 417 (82.6) years). Infection, cardiac arrhythmias, and right ventricular
Diuretic 435 (84.5) 460 (91.1) failure were similar between the groups. Serious adverse
β-blocker 284 (55.1) 269 (53.3)
event rates during the extended phase from 2 to 5 years are
shown in eTable 6 in Supplement 2.
Angiotensin-converting 158 (30.7) 171 (33.9)
enzyme inhibitor
or angiotensin II
receptor antagonist Functional Status
Intraaortic balloon pump 64 (12.4) 75 (14.9) Although NYHA class was collected in only 178 patients and
6MWD in only 89 patients at 5 years, the available data showed
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided
similar results between the treatment groups. At 5 years, 74
by height in meters squared).
a of 109 patients (67.9%) in the centrifugal-flow pump group and
Race and ethnicity were self-reported according to the predefined categories
shown. 48 of 69 (69.6%) in the axial-flow pump group were in NYHA
b
Includes self-reported descriptors such as Hispanic, Latino, Mexican, class I or II (eTable 7 in Supplement 2).
Caribbean-American, Middle Eastern, Multi-racial, and Native American.
c
Cardiac function and pressures were evaluated by invasive hemodynamic Post Hoc End Points and Analyses
assessment. Reference values were as follows: mean arterial pressure,
Cause-Specific Mortality
70-105 mm Hg; pulmonary-capillary wedge pressure, 6-12 mm Hg; cardiac
index, 2.2-4 L/min/m2; pulmonary vascular resistance, ⱕ3 Wood units; right The causes of death are shown in eTable 8 in Supplement 2.
atrial pressure, 0-5 mm Hg. In the axial-flow pump group, there were 54 deaths due to he-
d
Laboratory reference values were as follows: serum sodium, 135-145 mmol/L; mocompatibility-related adverse events, which were the lead-
serum creatinine, 0.8-1.3 mg/dL; estimated glomerular filtration rate, ing causes of death. In the centrifugal-flow pump group, the
>60 mL/min/1.73 m2.
risk of hemocompatibility-related mortality was significantly
e
Interagency Registry for Mechanically Assisted Circulatory Support
lower than in the axial-flow pump group (3.9% vs 10.7%; HR,
(INTERMACS) profiles range from 1 to 7; a profile of 1 represents the most
severe illness and a profile of 7 represents the least severe illness. Profiles 0.33 [95% CI, 0.20-0.55]; P < .001), resulting from reduced
range from 1 to 3 in patients requiring inotropic therapy (ranging from unstable strokes and device thrombosis events (Figure 4). Heart fail-
to stable) and 4 to 7 in those without inotropic therapy but with symptoms ure was the next leading cause of death in both groups, fol-
including heart failure at rest and advanced New York Heart Association
class III.
lowed by infection. The risk of death due to these causes were
f
Moderate and severe valvular insufficiency were determined by the site
similar between treatment groups.
investigators based on echocardiography.
Competing Outcomes
The outcomes occurring in the centrifugal-flow pump and
composite end point is shown in eTable 4 in Supplement 2. axial-flow pump groups during the 5-year study are shown in
Censoring of patients who refused consent for extended eFigure 2 in Supplement 2. At the completion of the 5-year
follow-up at 2 years (instead of the date of refusal) did not sig- follow-up, 141 of 515 patients (27.4%) in the centrifugal-flow
nificantly change the 5-year event-free survival rates. pump group and 85 of 505 (16.8%) in the axial-flow pump group
remained receiving LVAD support. Of all 1020 patients, 322
Overall Survival (31.6%) underwent heart transplant. Survival in the presence
During the 5-year follow-up period, 156 of 515 patients (30.3%) of the competing risk of transplant was evaluated with the Fine-
in the centrifugal-flow pump group and 184 of 505 (36.4%) in Gray model, and the mortality risk continued to remain sig-
the axial-flow pump group died. At 5 years, the Kaplan-Meier nificantly lower with the centrifugal-flow pump compared with
overall survival rates were 58.4% in centrifugal-flow pump the axial-flow pump (HR, 0.78 [95% CI, 0.63-0.97]; P = .023).
group and 43.7% in axial-flow pump group (HR, 0.72 [95% CI, In the subgroup of patients in whom the intended goal for
0.58-0.89]; P = .003) (Figure 2B). In a post hoc analysis, there therapy was bridge to transplant or bridge to candidacy for
were consistent findings in the destination therapy–specific transplant, the transplant rates were 102 of 198 patients (51.5%)
subgroup, with a 5-year Kaplan-Meier survival rate of 54.8% in the centrifugal-flow group and 110 of 198 (55.6%) in the

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 Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices Original Investigation Research

Figure 2. Composite End Point and Overall Survival in a Study of 5-Year Outcomes in Patients With Fully Magnetically Levitated
vs Axial-Flow Left Ventricular Assist Devices (LVADs)

A Composite end point B Overall survival

100 100

Centrifugal-flow pump
80 80

Survival probability, %
Event-free survival, %

Centrifugal-flow pump
Axial-flow pump
60 60

Axial-flow pump
40 40

20 20

Hazard ratio at 5 y, 0.55 (95% CI, 0.45-0.67); P <.001 Hazard ratio at 5 y, 0.72 (95% CI, 0.58-0.89); P = .003
0 0
0 1 2 3 4 5 0 1 2 3 4 5
Time after implant, y Time after implant, y
No. of patients
Centrifugal-flow pump 515 373 280 208 177 138 515 383 289 213 184 141
Axial-flow pump 505 321 223 147 106 71 505 339 247 165 124 85

A, Comparison of survival to transplant, recovery, or LVAD support free of
debilitating stroke (Modified Rankin Scale score >3) or reoperation to replace
the pump 5 years after the implant. The 5-year event-free survival was 54.0%
(95% CI, 48.5%-59.1%) in the magnetically levitated centrifugal-flow pump
group and 29.7% (95% CI, 24.7%-34.9%) in the axial-flow pump group. Patients
receiving transplants for reason other than device malfunction are censored at
time of transplant assuming there was no prior pump replacement or
debilitating stroke. B, Five-year survival was 58.4% (95% CI, 52.8%-63.6%) in
the centrifugal-flow pump group and 43.7% (95% CI, 37.6%-49.6%) in the
axial-flow pump group. Patients who received transplants were censored at
time of transplant. The median (IQR) LVAD support duration was 2.01
(0.94-5.0) years for the centrifugal-flow pump group and 1.86 (0.75-3.98) years
for the axial-flow pump group. In the extended phase after 2 years, a total of
477 patients contributed data to these analyses.

Figure 3. Serious Adverse Events in a Study of 5-Year Outcomes in Patients With Fully Magnetically Levitated
vs Axial-Flow Left Ventricular Assist Devices

Events/patient-years
Centrifugal-flow Axial-flow pump Favors Favors
pump (515 patients; (505 patients; Rate ratio centrifugal-flow axial-flow
Serious adverse event 1234 patient-years) 997 patient-years) (95% CI) pump pump P valuea
Any bleeding 0.430 0.765 0.56 (0.50-0.63) <.001
Gastrointestinal bleeding 0.252 0.423 0.60 (0.51-0.69) <.001
Any stroke 0.050 0.136 0.37 (0.27-0.50) <.001
Suspected or confirmed pump thrombosis 0.010 0.108 0.09 (0.05-0.16) <.001
Any major infection 0.515 0.551 0.94 (0.83-1.05) .25
Cardiac arrhythmia 0.207 0.283 0.73 (0.62-0.87) <.001
Right heart failure 0.149 0.146 1.02 (0.82-1.27) .87
Other neurologic eventb 0.073 0.065 1.12 (0.81-1.54) .49

0.05 0.1 1 4
Rate ratio (95% CI)

Serious adverse events are defined as those causing death or congenital axial-flow pump group. Other secondary end points are shown in eTable 6 and 7
abnormality or birth defect or a life-threatening illness or injury that results in in Supplement.
permanent disability, requires hospitalization, or prolongs a hospitalization a
Rate ratios and P value from Poisson regression.
and/or requires intervention to prevent permanent injury or damage. b
Includes encephalopathy, seizure, transient ischemic attack, and other
Serious adverse events occurring after 2 years were collected in 178 patients in
neurological events other than stroke.
the magnetically levitated centrifugal-flow pump group and 117 patients in the

axial-flow pump group (eFigure 3 in Supplement 2). Of these
396 patients, 85 (21.5%) died before receiving a transplant. In
addition, a portion of patients in whom the initial goal for
therapy was destination therapy (54 of 317 [17.0%] in the cen-
trifugal-flow pump group and 56 of 307 [18.2%] in the axial-
flow pump group) were eventually put on a transplant list and
received a transplant (eFigure 4 in Supplement 2). Because
some patients in whom the intended goal was destination
therapy ultimately received a transplant, survival was reevalu-
ated in the destination therapy subgroup excluding patients
who received a transplant (eFigure 5 in Supplement 2). In this
subgroup of patients who underwent destination therapy, a sig-
nificant survival benefit with the centrifugal-flow pump was
demonstrated (HR, 0.70 [95% CI, 0.55-0.89]; P = .004).
Subgroup Analysis of Survival
No significant interaction between the groups was observed
for the prespecified subgroups of age, sex, race and ethnicity,

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 Research Original Investigation Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices
Figure 4. Cause-Specific Mortality 5 Years After Implant in a Study of Patients With Fully Magnetically Levitated
vs Axial-Flow Left Ventricular Assist Devices
No. (%)
Centrifugal-flow Axial-flow
Cause of death pump (n = 515) pump (n = 505)
Hemocompatibility-related event 20 (3.9) 54 (10.7)
(device thrombosis, stroke, bleeding)
Heart failure 47 (9.1) 43 (8.5)
Infection 26 (5.0) 26 (5.1)
Otherc 63 (12.2) 61 (12.1)
Comparison of deaths due to hemocompatibility-related events, heart failure,
infection, and other causes. In the extended phase after 2 years, a total of 477
patients contributed data to the analysis.
a
Difference shown for magnetically levitated centrifugal-flow pump minus
axial-flow pump values.
intended goal of pump support (bridge to transplant or destina-
tion therapy), or INTERMACS profile with regard to overall sur-
vival (eFigure 6 in Supplement 2). Thus, the treatment effect with
respect to survival was consistent across different subgroups.
Tipping Point Sensitivity Analysis
The tipping point δ was between 3 and 4, which indicated that
the mortality hazard of the patients in the centrifugal-flow
pump group that were withdrawn would have to be at least
3-fold greater than those who were not withdrawn to abolish
the centrifugal-flow pump survival benefit compared with the
axial-flow pump.
Discussion
In this observational follow-up study of patients from the IDE
trial, per-protocol analyses found that implantation of a fully
magnetically levitated LVAD vs axial-flow LVAD was associ-
ated with a better composite outcome and higher likelihood
of overall survival at 5 years. These findings support the use
of the fully magnetically levitated LVAD.
Unlike the pivotal 2-year analysis, there was higher like-
lihood of overall survival in patients who received the cen-
trifugal-flow pump compared with the axial-flow pump at this
5-year time point. The statistically significant difference in sur-
vival was attributable to fewer deaths due to hemocompat-
ibility-related adverse events, including stroke, bleeding, and
pump thrombosis. The median survival in patients in the cen-
trifugal-flow pump group with advanced heart failure ex-
ceeded 5 years, including the subgroup who received an LVAD
with a therapeutic intent of destination therapy and were
deemed ineligible for cardiac transplant at the time of enroll-
ment in the trial.
Engineering advances have introduced technologically
improved LVADs in the past 2 decades with a gain in 2-year
survival. 3,6,7 The Randomized Evaluation of Mechanical
Assistance for the Treatment of Congestive Heart Failure
(REMATCH) trial investigated an early-generation LVAD
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Favors Favors
Difference, % Hazard ratio centrifugal-flow axial-flow
(95% CI) %a (95% CI) pump pump P valueb
–6.8 (–10.0 to -3.6) 0.33 (0.20-0.55) <.001
0.6 (–2.9 to 4.1) 1.01 (0.67-1.53) .95
–0.1 (–2.8 to 2.6) 0.92 (0.54-1.59) .77
0.0 (–4.1 to 4.0) 0.94 (0.66-1.33) .72
0.2 1 2
Hazard ratio (95% CI)
b
Hazard ratios and P values were calculated from the Fine-Gray model.
c
Other causes are provided in eTable 8 in Supplement 2. The most common
other causes included ventricular arrhythmia or cardiac arrest, trauma, hepatic
or kidney failure, respiratory failure, and driveline or power cable
disconnection.
(HeartMate vented electric device, Thoratec) compared with
optimal medical therapy and demonstrated a 23% survival
with the LVAD at 2 years. 8 This represented a marked
improvement over that expected in a cohort of transplant-
ineligible patients with advanced heart failure (8% survival at
2-year in the medical therapy group). A randomized clinical
trial of a continuous-flow pump compared with the older-
generation pulsatile-flow LVAD used in the REMATCH trial
demonstrated a significant improvement in survival of 58%
at 2 years. 9 Another centrifugal-flow pump that did not
require an abdominal surgical pocket and could be implanted
directly in the thorax, the Heartware HVAD (Medtronic) was
deemed to be noninferior to the axial-flow pump with a simi-
lar survival at 2 years.10 However, these devices have had
hemocompatibility-related adverse events, with a dominance
of pump thrombosis in the axial-flow pump group and stroke
events in the HVAD group.11,12 The centrifugal-flow pump
was engineered to reduce hemocompatibility-related adverse
events by increasing the blood flow pathways and developing
an intrinsic pulsatility in the pump while using a frictionless
fully magnetically levitated rotor system.13-15
Until this trial, registry analyses such as INTERMACS have
provided the best look at 5-year survival, but their analyses
have been dominated by devices other than the centrifugal-
flow pump. Estimates from those analyses indicated an over-
all survival of 48.2% in the current era, but lower, at 40.6%,
in the destination therapy subgroup at 5 years.16,17 These sur-
vival estimates are concordant with the observed survival in
the axial-flow pump group in the current trial.
In the current trial, adverse events and deaths due to heart
failure, followed by infection, remained dominant with the cen-
trifugal-flow pump LVAD. There continues to be concerns about
hemodynamic-related adverse events (heart failure) and mor-
bidity of device-related infection.18-20 Clinical algorithms that
utilize invasive hemodynamic assessments in concert with car-
diac and device-based imaging may be required to discrimi-
nate the associated causes of heart failure and to target therapy
toward the primary underlying deficit.17 These may include
speed adjustments to facilitate left ventricular unloading,
jama.com
 Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices Original Investigation Research

amelioration of aortic regurgitation (which can result in recir-
culation), or assessing for defects such as obstruction of the
outflow graft. Dealing with driveline-related infections may re-
quire engineering of fully internalized power sources through
transcutaneous energy transfer or other techniques.3
Limitations
This study has several limitations. First, as a result of the op-
erational challenges in this trial due to the gap between comple-
tion of the pivotal trial, the need to initiate a separate study
protocol, and challenges encountered due to the unantici-
pated occurrence of the COVID-19 pandemic, there was a high
percentage of missing data for the originally intended pri-
mary end point and serious adverse events. This required modi-
fying the principal end point analysis to focus on survival,
which provided the most complete information in this study.
However, the rates of nonfatal events in end points should be
interpreted carefully due to the magnitude and imbalance of
missingness of values between the treatment groups. Sec-
ond, data to define the accompanying quality of life experi-
enced during device therapy were not collected, making cost-
effectiveness assessment difficult.21 Third, some researchers
may consider the clinical trial population as different from
those in the clinical setting. However, a previous investiga-
tion that examined this issue concluded that most exclusion
criteria used in LVAD clinical trials did not afford a substan-
tially greater risk to patients in the clinical setting. The out-
comes in the axial-flow pump LVAD group were similar to those
reported in INTERMACS.22 Fourth, not all initial centers chose
to continue the extended 5-year follow-up. However, the spon-
sor device tracking database was used to reduce the dropout
rates in a sensitivity analysis.
Conclusions
In this observational follow-up study of patients from the IDE
trial, per-protocol analyses found that receipt of a fully mag-
netically levitated LVAD vs axial-flow LVAD was associated a
better composite outcome and higher likelihood of overall sur-
vival at 5 years. These findings support the use of the fully mag-
netically levitated LVAD.

ARTICLE INFORMATION
Accepted for Publication: August 23, 2022.
Published Online: September 8, 2022.
doi:10.1001/jama.2022.16197
Author Affiliations: Brigham and Women’s
Hospital, Boston, Massachusetts (Mehra);
Montefiore Einstein Center for Heart and Vascular
Care, New York, New York (Goldstein); University of
Colorado School of Medicine, Aurora (Cleveland);
Henry Ford Hospitals, Detroit, Michigan (Cowger);
Baylor University Hospital, Dallas, Texas (Hall);
University of Chicago, Chicago, Illinois (Salerno);
Columbia University College of Physicians and
Surgeons and NewYork-Presbyterian Hospital, New
York, New York (Naka, Uriel); Weill Cornell Medical
College, New York, New York (Naka); INTEGRIS
Baptist Medical Center, Oklahoma City, Oklahoma
(Horstmanshof); Abbott, Abbott Park, Illinois
(Chuang, Wang).
Author Contributions: Drs Mehra and Uriel had full
access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Concept and design: Mehra, Cleveland, Cowger,
Hall, Salerno, Uriel.
Acquisition, analysis, or interpretation of data:
Mehra, Goldstein, Cleveland, Cowger, Salerno,
Naka, Horstmanshof, Chuang, Wang, Uriel.
Drafting of the manuscript: Mehra, Chuang.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Mehra, Goldstein, Wang.
Administrative, technical, or material support:
Salerno, Chuang.
Supervision: Mehra, Cleveland.
Other - comments on images, verbiage, word count,
etc: Cowger.
Other - National Co-PI of the study: Uriel.
Conflict of Interest Disclosures: Dr Mehra
reported receiving payment made to his institution
from Abbott for consulting during the conduct of
the study; personal fees from Baim Institute for
clinical research as a clinical events committee
member, Natera for academic consulting, Paragonix
for academic consulting, Transmedics for serving as
an advisory board member, NupulseCV for serving
as an advisory board member, FineHeart for serving
as an advisory board member, Leviticus for serving
as an advisory board member, personal fees from
Janssen for serving as a steering committee
member, Moderna for serving as a clinical endpoint
committee member, and Mesoblast for serving as a
data and safety monitoring board member outside
the submitted work. Dr Goldstein reported
receiving personal fees from Abbott for consulting
and personal fees from Abiomed for serving as a
consultant and speaker outside the submitted
work. Dr Cleveland reported receiving grants from
Abbott Medical during the conduct of the study and
personal fees from Abbott for serving as a medical
chair of the clinical events committee on the ARIES
trial and grants from Medtronic outside the
submitted work. Dr Cowger reported receiving
personal fees from Abbott for serving on a
publication committee as a consultant during the
conduct of the study and nonfinancial support from
Abbott for serving on an advisory board, receiving
travel-related compensation, serving as a speaker
(all for left ventricular assist devices) and serving on
a steering committee for Tendyne and Cephea
valves; receiving personal fees from Medtronic for
serving as a study national primary investigation
and consultant (HVAD device); serving on a data
and safety monitoring board for Bivacor; and
receiving personal fees from Corwave for serving as
a consultant outside the submitted work. Dr Hall
reported receiving personal fees for consulting
from Abbott, Abiomed, Medtronic, CareDx, and
Natera outside the submitted work. Dr Salerno
reported receiving personal fees from Abbott for
serving as a consultant and speaker during the
conduct of the study and personal fees from Abbott
outside the submitted work. Dr Naka reported
receiving speaker fees from Nipro outside the
submitted work and serving as a consultant for the
past 36 months without payment for Abbott,
Zimmer-Biomet, and CryoLife. Dr Horstmanshof
reported receiving personal fees from Abbott
Medical outside the submitted work. Dr Chuang
reported receiving salary as a paid employee of
Abbott during the conduct of the study. Dr Wang
reported receiving salary for being an employee of
Abbott during the conduct of the study. Dr Uriel
reported receiving grants from Abbott, Abiomed,
and Fire 1 and serving on a medical advisory board
Livemetric, Leviticus, and Revamp outside the
submitted work.
Funding/Support: This study was sponsored by
Abbott Laboratories.
Role of the Funder/Sponsor: The sponsor had a
role in design of the study, selection of centers, data
collection, and analyzing study data. The decisions
on manuscript development and submission were
within the primary purview of the academic
investigators. The manuscript writing, revision, and
decision to submit for publication were driven by
the trial publications and presentation committee.
The sponsor did not control the decision to which
journal the manuscript was submitted. The sponsor
approved the manuscript prior to submission. The
manuscript was written by the first author, all
versions fully controlled by him in collaboration
with the other authors. The sponsor assisted with
data requests under the direction of the
corresponding author. An independent statistician
responsible to the publications and presentation
committee accessed, verified and validated the
study findings.
Data Sharing Statement: See Supplement 3.
Additional Contributions: Joseph Massaro, PhD
(Boston University, Boston, Massachusetts), served
as the independent statistician for the MOMENTUM
3 trial and this analysis and was compensated for
this work.
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