Does Small Size Matter With Continuous Flow Devices?

JACC: HEART FAILURE

VOL.

ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

-, NO. -, 2016

ISSN 2213-1779/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jchf.2016.09.009

Does Small Size Matter With Continuous Flow Devices? Analysis of the INTERMACS Database of Adults With BSA #1.5 m2 Farhan Zafar, MD,a Chet R. Villa, MD,a David L. Morales, MD,a Elizabeth D. Blume, MD,b David N. Rosenthal, MD,c James K. Kirklin, MD,d Angela Lorts, MDa

ABSTRACT OBJECTIVES This study investigated how small patient size affects clinical outcomes in patients implanted with a continuous flow left ventricular assist device (CFLVAD). BACKGROUND The development of smaller CFLVADs has allowed ventricular assist device (VAD) use in anatomically smaller patients; however, limited outcome data exist regarding CFLVAD use in patients with a body surface area (BSA) #1.5 m2. METHODS All CFLVAD patients entered in the Interagency Registry for Mechanically Assisted Circulatory Support registry April 2008 to September 2013 and with BSA data were included. Biventricular VAD patients were excluded. Patient characteristics and clinical outcomes were compared between patients with BSA #1.5 m2 (small patients) and those >1.5 m2. RESULTS Of 10,813 CFLVAD recipients, 231 had a BSA #1.5 m2. Small patients were more commonly female patients (68% vs. 20%; p < 0.01), Hispanic (10% vs. 6%; p < 0.03), and on intravenous inotropes (88% vs. 80%; p < 0.01). Small patients had higher bleeding (p < 0.01) and driveline infection (p < 0.01) rates, while exhibiting lower rates of right heart failure (p < 0.01) and renal dysfunction (p < 0.01). Device malfunction rate (p > 0.05), overall survival (p > 0.05), and 1-year competing outcomes (p > 0.05) were similar between BSA groups. CONCLUSIONS Patients with a BSA #1.5 m2 supported with a CFLVAD have similar survival to larger patients. These data support the use of CFLVAD in anatomically small patients. (J Am Coll Cardiol HF 2016;-:-–-) © 2016 by the American College of Cardiology Foundation.

V

entricular

have

number of patients with a body surface area

revolutionized the treatment of end-stage

assist

devices

(VADs)

(BSA) #1.5 m 2 in the HeartMate II (Thoratec Inc., Pleas-

heart failure. The increased utilization that

anton, California) and HeartWare (HeartWare Inc., Fra-

has been seen in the past 5 years has been accelerated

mingham, Massachusetts) clinical trials and continued

by the transition from historic large, pulsatile VADs to

access protocols (5–8). In addition, the instructions for

the newer, smaller, continuous flow pumps (1,2). His-

use for each device specifically state that the safety

torically, women and children have been underserved

and effectiveness of the devices have not been estab-

by VAD therapy despite favorable VAD outcomes in

lished in patients with a BSA #1.5 m 2. In spite of the la-

these populations (3,4). Multiple reasons exist for the

beling and limited data, the use of continuous flow

lower VAD utilization rates in these patients; however,

devices has rapidly expanded to smaller patients

small patient size is one of the most frequently cited

(9–13), including children (14) with BSAs as low as

causes. The size concerns are reflected in the small

0.7 m 2, because there are no ideal alternative therapies.

From the aCincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; bBoston Children’s Hospital, Boston, Massachusetts; c

Lucile Packard Children’s Hospital, Palo Alto, California; and the dUniversity of Alabama at Birmingham, Birmingham, Alabama.

Data collection for this work was funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN268201100025C. Dr. Morales has served as a consultant for Syncardia. Dr. Rosenthal has received research funds from Berlin Heart and educational support from Heartware. Drs. Zafar and Villa contributed equally to this work. Manuscript received July 21, 2016; revised manuscript received September 6, 2016, accepted September 11, 2016.

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ABBREVIATIONS

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VADs in Patients With a BSA #1.5 m2

Given the limited data assessing the safety

the 2 groups. Because of the deidentified nature of the

of these devices in small adults, this study

dataset, age was available only in groups of 10-year

sought to characterize the use of continuous

periods. The primary outcome was all cause-morality

flow left VADs (CFLVADs) in patients with a

with data censored at transplantation or device

BSA #1.5 m2 and to describe the differences

explanation for myocardial recovery. Secondary out-

in clinical outcome associated with the use of

comes were major adverse events measured both as

CFLVADs in these “undersized” patients. On

events per 100 patient months and time to first major

the basis of the positive clinical experience to

bleeding, device malfunction, infection, neurological

Mechanically Assisted

date (9,11–13), we hypothesized patients with

dysfunction, renal dysfunction, and right heart failure

Circulatory Support

a BSA #1.5 m 2 would have similar survival to

(RHF) (15). Bleeding event was further classified by

RHF = right heart failure

larger patients. In addition, we thought it

site: mediastinal, gastrointestinal, and others. The

AND ACRONYMS BSA = body surface area CFLVAD = continuous flow left ventricular assist device

FDA = Food and Drug Administration

INTERMACS = Interagency for

possible that the morbidity profile would

“Bleeding: others” category included bleeding from

differ given both the expected demographics and

the pump pocket, pleural space, abdominal, pulmo-

chest/device size mismatch for patients with a

nary, retroperitoneal, urinary tract, and ear-nose-

BSA #1.5 m2 .

throat/dental. Similarly, infection was also further

VAD = ventricular assist device

classified by location: pump related (pocket and pump

METHODS

interior), driveline, and others. The “Other infection”

Data for this study were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support

(INTERMACS)

Registry,

funded

by

the

category included line sepsis, pulmonary, urinary tract,

mediastinum,

peripheral

wound,

and

gastrointestinal.

National Heart, Lung, and Blood Institute, National

STATISTICAL ANALYSIS. Categorical characteristics

Institutes of Health, Department of Health and Human

were compared using chi-square test or Fischer’s

Services, under Contract No. HHSN268201100025C.

exact test as appropriate. Continuous variables were

The INTERMACS database is a national registry

compared using the Mann-Whitney U test. The

sponsored by National Heart, Lung, and Blood Insti-

primary endpoint was presented as a competing

tute to collect data on patients treated with U.S. Food

outcome analysis (transplant, recovery, alive on de-

and Drug Administration (FDA)-approved mechanical

vice, or death) using time to transplant, recovery, or

circulatory support devices for the treatment of

death. Favorable outcomes (transplanted, recovered,

advanced heart failure. Participation is mandatory for

alive with device in place) were compared at 1 year

Centers for Medicare & Medicaid Services–approved

and overall using the chi-square test. Freedom from

mechanical circulatory support implantation centers.

first episode of major adverse events was compared

The data are audited, and adverse events are reviewed

using the Kaplan-Meier method. The exact event rate

and validated by a Medical Events Committee. A

per 100 patient months and 95% confidence intervals

project-specific research proposal was reviewed and

for each major adverse event were estimated using

approved by INTERMACS data coordinating center

the Byar method and compared using z-test statistics

before the release of a completely deidentified dataset

between the 2 groups. All the statistics was performed

for this study.

using SPSS, version 21 (IBM Corporation, Armonk,

STUDY POPULATION. The INTERMACS registry was

used to identify all adults (>18 years) implanted with a CFLVADs from April 2008 to September

New York).

RESULTS

2013. Patients (117) with missing BSA and sex

BASELINE CHARACTERISTICS BY BSA. A total of 231

information were removed. Patients (329) with

(2%) small patients (BSA #1.5 m 2) received a CFLVAD

biventricular VAD implants were also excluded from

during the study period compared with 10,582 (98%)

the study. The remaining (10,813) patients were

standard patients (BSA >1.5 m 2). The patient size

divided into 2 cohorts based on BSA: “standard” patients with BSA >1.5 m 2 (matching fit criteria for at least 1 of the FDA-approved continuous flow [CF] devices) and “small” patients with BSA #1.5 m 2 (not matching fit criteria for any FDA-approved CF devices) (9,10). PATIENT

CHARACTERISTICS

distribution is shown in Figure 1. Pre-implant characteristics, device strategies, and clinical and laboratory values are compared in Table 1. The small patients were more likely to be women, Hispanic, and on intravenous inotropes at the time of implant. Age, diagnosis, INTERMACS profile, and biventricular VAD

AND

OUTCOMES. Pre-

use were similar between the 2 groups. Smaller pa-

implant characteristics, implantation strategies, and

tients were more commonly in the group deemed

clinical and laboratory data were compared between

unlikely to be listed (5% vs. 3%; p ¼ 0.05). There were

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VADs in Patients With a BSA #1.5 m2

F I G U R E 1 Patient Body Size in Each Size Cohort

BSA ¼ body surface area; IQR¼ interquartile range.

only 15 patients with BSA #1.2 m 2 and only 1 patient

rather than women (9.5 events/100 patient months

with a BSA <1.0 m 2 (0.76 m 2).

vs. 6.0 events/100 patient months; p < 0.01), and

SURVIVAL. Overall survival was similar between the

number of bleeding events were similar between

2 groups (Table 2). One-year competing outcomes

women with BSA #1.5 m 2 and >1.5 m 2 (5.06 events/

were favorable in 81% of the small patients (15%

100 patient months vs. 5.92 events/100 patient

transplanted, 1% recovered, and 65% alive on device)

months; p ¼ 0.66).

and was similar to standard patients (p ¼ 0.8). How-

The localized driveline infection rate was signifi-

ever, fewer small patients were transplanted at 1 year

cantly higher in the small patients compared with

compared with standard patients (15% vs. 23%;

standard patients (1.9 events/100 patient months vs.

p < 0.01) (Figure 2). Cause of death was similar be-

1.4 events/100 patient months; p ¼ 0.01). There was

tween the 2 groups except for major infection (1.8%

no difference in pump or other infection rates. There

vs. 9.2%; p ¼ 0.05) (Online Table 1).

was no difference in infection rates based on sex in the small patient cohort (6.4 events/100 patient

ADVERSE EVENTS. The major adverse event rates are

months vs. 7.0 events/100 patient months; p ¼ 0.48).

presented in Table 3 and time to first event in

Infection rates were also similar between women with

Figure 3. Overall bleeding rate was higher in small

BSA #1.5 m2 and >1.5 m 2 (6.4 events/100 patient

patients

months vs. 6.8 events/100 patient months; p ¼ 0.39).

compared

with

standard

patients

(7.0

events/100 patient months vs. 5.9 events/100 patient

The

small

patients

experienced

less

renal

months; p < 0.01). Small patients had higher rates of

dysfunction (0.6 events/100 patient months vs. 1.1

gastrointestinal bleeding and other site bleeding;

events/100 patient months; p ¼ 0.01) and RHF (0.2

however, there was no difference in mediastinal

events/100 patient months vs. 0.5 events/100 patient

bleeding. The higher number of bleeding events in

months; p ¼ 0.01). No small patients experienced

the small patient cohort occurred primarily in men

early RHF (<1 month). The small patients also had

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VADs in Patients With a BSA #1.5 m2

Time-to-event analysis showed that there was no

T A B L E 1 Baseline Characteristics

difference in freedom from first bleeding event, renal Pre-Implant BSA #1.5 m 2 (n ¼ 231)

Pre-Implant BSA >1.5 m 2 (n ¼ 10,582)

dysfunction, infection, and RHF (Figure 3), despite p Value

differences in the overall event rates noted previ-

Age (<60 yrs)

119 (51.5)

5,594 (52.9)

0.685

ously. There was also no difference in freedom from

Women

156 (67.5)

2,135 (20.2)

<0.001

device malfunction (p ¼ 0.62) and neurological

Hispanic

24 (10.4)

647 (6.1)

0.025

Blood type O

101 (43.7)

5,041 (47.6)

0.239

dysfunction (p ¼ 0.57).

BSA (m2)

1.39  0.1

2.07  0.27

<0.001

Concomitant surgery

88 (38.3)

4,116 (38.9)

0.835

NYHA functional class IV

177 (76.6)

7,748 (73.3)

0.247

15 (6.5)

571 (5.4)

0.466

Dialysis (past 48 h)

3 (1.3)

155 (1.5)

0.835

difference in mortality for patients in the INTERMACS

IV inotrope therapy

204 (88.3)

8497 (80.3)

0.008

registry with a BSA #1.5 m 2 compared with patients

CAD

10 (4.3)

657 (6.2)

0.240

strated no early RHF and lower rates of late RHF

Diabetes

15 (10.9)

496 (9.3)

0.506

Smoker

8 (5.8)

242 (4.5)

0.467

compared with patients with a BSA >1.5 m 2, but did

Ventilator (past 48 h)

DISCUSSION The current study found there was no significant

with a BSA >1.5 m 2. The smaller patients demon-

Comorbidities

INTERMACS

experience higher rates of nonmediastinal bleeding and driveline infection. Despite incremental differ-

1. Critical cardiogenic shock

38 (16.5)

1,492 (14.1)

0.311

2. Progressive decline

88 (38.1)

4,025 (38.0)

0.985

ences in these outcomes, overall survival was similar

3. Stable but inotrope dependent

70 (30.3)

3,049 (28.8)

0.621

between small and standard size patients. These data

4. Resting symptoms

30 (13.0)

1,500 (14.2)

0.608

support the continued use of these continuous flow

5. Exertion intolerant

3 (1.3)

304 (2.9)

0.154

devices in small patients.

6. Exertion limited

1 (0.4)

136 (1.3)

0.252

7. Advanced NYHA functional class III

1 (0.4)

76 (0.7)

0.610

BTT: listed

61 (26.4)

2,867 (27.1)

0.816

BTT: likely to be listed

51 (22.1)

2,263 (21.4)

0.800

BTT: moderate likely to be listed

24 (10.4)

1,021 (9.6)

0.706

well as the recent report from the Pediatric Inter-

Device strategy

The

finding

that

survival

is

similar

in

patients #1.5 m2 is notable given the rise of CFLVAD technology and the increasing use of these devices in small adults and children (2). The current data as

BTT: unlikely to be listed

12 (5.2)

314 (3.0)

0.050

agency Registry for Mechanical Circulatory Support

Destination therapy

81 (35.1)

4,006 (37.9)

0.387

(PediMACS) (13) provide the most robust data to

2 (0.9)

72 (0.7)

0.830

date that CFLVADs can safely and effectively sup-

135  5

135  5

0.375

1.2  0.6

1.42  0.73

<0.001

Total cholesterol (mg/dl)

133.0  43.2

135.3  176.8

0.288

WBC (103/ml)

8.51  4.87

8.50  3.98

0.411

been underserved because of small body size,

209  87

198  81

0.030

including women, non-Caucasian ethnicities, and

VAD indication: failure to wean CPB Laboratory testing Sodium (mmol/l) Creatinine (mg/dl)

Platelet (10 /ml) 3

port small patients. The smaller footprint of currentgeneration CFLVADs has allowed these devices to be implanted in populations that have traditionally

1.30  0.41

1.33  0.44

0.072

children (11,12,14,16,17). The lower rates of VAD

BNP (pg/ml)

1,703  1,431

1,151  1,088

<0.001

utilization and delay in the use of VAD therapy

Prealbumin (mg/dl)

17.81  6.27

18.82  7.47

0.189

within these populations have also been linked to

Albumin (g/dl)

3.42  0.61

3.40  0.67

0.654

higher waitlist mortality (18,19). Although the in-

INR

dustry instructions for use for the most common

Values are n (%) or mean  SD. BNP ¼ brain natriuretic peptide; BSA ¼ body surface area; BTT ¼ bridge to transplant; INR ¼ international normalized ratio; INTERMACS ¼ Interagency Registry for Mechanically Assisted Circulatory Support; NYHA ¼ New York Heart Association; VAD ¼ ventricular assist device.

CFLVADS still cite a BSA of 1.5 m 2 as their lower size recommendation, the lack of therapeutic alternatives has driven the use of these devices in small patients despite the limited data. The current study provides some reassurance that CFLVADs are safe

lower rates of late RHF (>1 month) compared with

and effective in patients with a BSA #1.5 m2 as

standard size patients (0.2 events/100 patient months

outcomes are favorable and similar to those of larger

vs. 0.4 events/100 patient months; p ¼ 0.04).

patients. Of note, the small patients included in this

The rate of all other major adverse events,

study were not significantly older, did not undergo

system

VAD implantation at a less favorable INTERMACS

thrombus, device malfunction, hemolysis, hepatic

patient profile, and had similar indications for im-

dysfunction, neurological dysfunction, stroke, reho-

plantation (35% vs. 37% implanted as destination

spitalization, and wound dehiscence, were not

therapy). The smaller patients were more likely to

different between the 2 groups (p > 0.3).

be on inotropes (88% vs. 80%) at the time of

including

arterial

noncentral

nervous

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VADs in Patients With a BSA #1.5 m2

(24,25). Assessing the risk of infection in small pa-

T A B L E 2 Clinical Outcome by Size Cohort

tients is likely not possible from the existing data

Outcome

BSA #1.5 m 2 (n ¼ 231)

BSA >1.5 m2 (n ¼ 10,582)

Total Cohort (n ¼ 10,813)

Transplant

49 (21.2)

2,796 (26.4)

2,845 (26.3)

Recovery Alive Death

5 (2.2)

given that the patients in the majority of studies have a median BSA in the 1.8 to 2.0 m2 range. We suspect the relationship between patient size and

125 (1.2)

130 (1.2)

120 (51.1)

4,989 (46.7)

5,109 (47.2)

infection risk is likely not linear, and attempts to

57 (24.7)

2,672 (25.3)

2,729 (25.2)

analyze the data may be confounded by risk of infection in obese patients (22). It may be that the

Values are n (%). There was no statistical difference in clinical outcomes between groups, p > 0.1.

risk of infection is in fact U-shaped (i.e., the risk for infection is higher in small and obese patients). However, even focused examination of studies including larger numbers of lower BSA patients has

implantation, suggesting that they may have waited

alternately reported smaller size as a risk factor for

longer before the decision was made to implant. The

infection (26,27) or not (28). It may be that a patient

patients with a BSA #1.5 m2 were also more likely to

who is “appropriately” small because of age, sex, or

be women (68%) compared with the larger patient

ethnicity will likely carry lower infectious risk profile

cohort (20%), although post-VAD survival has not

compared with a patient who is small because of

been shown to be different between men and

cardiac cachexia. Cachectic, or frail, patients could

women (3,16,20).

not be readily identified within the current dataset

Although the lack of a significant difference in

from rest of the cohort given the lack of patient-

mortality is the most notable finding within the

specific data or trends in the pre-implant data (pre-

current report, there were subtle differences in

albumin, weight, body mass index, etc.). Alternately,

adverse event rates that should be noted. First, small

there may be an inherent risk for driveline infection

patients experienced slightly higher rates of drive-

in smaller patients with less central adiposity or

line infection (1.9 events/100 patient months vs. 1.4

abdominal musculature; this will require further

events/100 patient months), although small patients

study. Small patients may require modified surgical

were less likely to have a major infection as the

technique (29) and exit site management protocols if

cause of death (1.6% vs. 9.2%). Of interesting, small

the current findings are confirmed in future studies.

patient size has not consistently been identified as a

Previous studies have reported success in lowering

risk factor for driveline infection. In fact, studies

driveline infections through a specific driveline care

reporting an association between infection and size

protocol (30); this may be especially relevant in

have generally identified larger size as a risk factor

smaller patients. There may also be an inherent risk

(21–23), although this association is inconsistent

for infection within the patient cohorts that is not

F I G U R E 2 Competing Outcomes by Size Cohort

BSA ¼ body surface area.

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VADs in Patients With a BSA #1.5 m2

anticoagulation management, which are not available

T A B L E 3 Adverse Event Rate by Size Cohort

in the current dataset.

BSA #1.5 m2

BSA >1.5 m2

p Value

7.36 (6.53–8.28)

6.09 (5.97–6.21)

<0.01

of RHF (0.19 events per 100 patient-months vs. 0.47

Bleeding: mediastinal

0.97 (0.68–1.33)

1.05 (1–1.1)

0.63

events per 100 patient-months), despite having a

Bleeding: GI

3.84 (3.24–4.51)

3.18 (3.1–3.27)

0.03

Bleeding: other

2.85 (2.34–3.43)

2.05 (1.98–2.12)

Adverse Event

Bleeding

<0.01

Third, patients with a BSA #1.5 m 2 had lower rates

higher proportion of women and more patients supported with inotropes at the time of implanta-

Arterial non-CNS thrombus

0.16 (0.06–0.34)

0.11 (0.09–0.12)

0.36

Device malfunction

1.91 (1.49–2.4)

1.76 (1.7–1.83)

0.51

tion, both of which have been reported as risk factors

Hemolysis

0.63 (0.4–0.93)

0.52 (0.49–0.56)

0.37

for post-VAD RHF (16,33,34). The lower rates of RHF

Hepatic dysfunction

0.42 (0.24–0.68)

0.43 (0.4–0.47)

0.88

in the small patient cohort are especially notable

Infection

7.03 (6.21–7.92)

5.94 (5.83–6.06)

0.01

given the theoretical potential for worsening RHF

Pump infection

0.31 (0.16–0.55)

0.23 (0.21–0.26)

0.32

with inappropriately high LVAD speed (for size) with

Driveline infection

1.91 (1.49–2.4)

1.41 (1.35–1.47)

0.02

Other infection

5.14 (4.45–5.92)

4.70 (4.6–4.81)

0.21

Neurological dysfunction

excessive left ventricular decompression and coincident septal shift (35). However, there is precedent

1.59 (1.22–2.05)

1.72 (1.66–1.78)

0.55

1.13 (0.81–1.53)

1.17 (1.11–1.22)

0.84

for lower rates of RHF, specifically, late RHF in

Rehospitalization

17.52 (16.22–18.9)

16.95 (16.75–17.15)

0.39

smaller patients. Takeda et al. (36), showed larger

Renal dysfunction

0.71 (0.46–1.03)

1.08 (1.03–1.13)

0.03

patients had higher rates of late RHF and renal

Right heart failure

0.24 (0.11–0.45)

0.47 (0.44–0.51)

0.03

dysfunction. The current study showed similar risks

Wound dehiscence

0.16 (0.06–0.34)

0.11 (0.1–0.13)

0.41

for the larger patient cohort, although, as with the

Stroke

Values are rate/100 patient-months (95% confidence interval). BSA ¼ body surface area; CNS ¼ central nervous system; GI ¼ gastrointestinal.

Takeda et al. (36) article, we are unable to discern which insult is primary, RHF or renal dysfunction. It is

reasonable

to

hypothesize

that

the

adverse

changes in right ventricular function associated with increasing patient size (37,38) are driving post-VAD assessed with the current data. The white blood cell

renal failure. The effect of device management,

count was similar between groups; however, infec-

especially pump speed, could not be assessed within

tious history, chronicity of heart failure, and frailty

the current data set.

were not assessed and may modify infectious risk (26,31).

Finally, although the focus of this study has been the clinical outcomes of VAD implantation in small

Second, the small patients experienced greater

adults, the data are also relevant to another tradi-

rates of bleeding, especially early in the postoperative

tionally underserved population: children. PediMACS

course, compared with the larger patients. The

recently reported the initial CFLVAD experience in

bleeding events occurred primarily in small men

children (13). Children supported with a continuous

rather than in women. The increased bleeding rate

flow VAD experienced an excellent overall outcome,

was not driven by higher rates of mediastinal

with a 92% favorable outcome at 6 months as well as

bleeding within the small patient cohort, which was a

favorable rates of bleeding, infection, renal dysfunc-

potential concern given the small thoracic cavity size

tion, stroke, and neurological dysfunction. Unfortu-

and resulting device/chest size mismatch. That

nately, the rate of RHF and specifics of bleeding and

women were not at particularly high risk of bleeding

infectious complications were not specifically re-

is especially notable given previous reports suggest-

ported in the initial PediMACS study and thus could

ing female sex (20,32) may increase the risk of

not be compared with the INTERMACS data. None-

bleeding complications. It is also notable that

theless, the combined data from the current study

although bleeding complications were higher within

and the PediMACS study provide further reassurance

the smaller group, there was no difference in the rates

that the use of current-generation VADs in small pa-

of thromboembolism, neurological dysfunction, or

tients should be considered. Although we believe the

device malfunction. These were all potential con-

data support implantation in smaller patients as a

cerns given that the CFLVADs were designed and

whole, the “safe” lower limit of patient size has not

optimized for patients with a BSA of w1.9 to 2.0 m 2.

yet been determined.

Running CFLVADs at lower rates per min (to accommodate for smaller patient size) could theoretically

STUDY LIMITATIONS. The INTERMACS registry pro-

increase the risk of thrombosis given lower flow rates

vides the most comprehensive method for assessing

through the device. The observed difference in

outcomes in specific populations that cannot be per-

coagulation-related complications may also be due to

formed at a single center. Thus, the INTERMACS

inherent differences in hemostasis or the details of

dataset provides a unique method to assess outcomes

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VADs in Patients With a BSA #1.5 m2

F I G U R E 3 Kaplan-Meier Curves Representing Freedom From Adverse Events by Size Cohort

BSA ¼ body surface area.

in a relatively small patient population (such as

adjusted analysis difficult. Thus, some of the differ-

patients with a low BSA); however, it is not without

ences in adverse event rates reported may reflect the

limitations. There is limited granularity regarding

differences in patient selection, characteristics, or

patient-specific

(especially

management rather than size. Specific pump throm-

regarding cardiac cachexia and frailty) that may pro-

clinical

variables

bosis data were not collected until 2014 and therefore

vide further clarity regarding the differences in

not analyzed in this study. Although less likely, given

adverse outcomes that are reported. There is also a

that a few statistical tests resulted in rejection of null

possibility of selection bias in that the small patients

hypothesis, the possibility of false-positive rate

who received a CFLVAD in the current study may not

cannot be excluded in multiple comparisons; no cor-

be reflective of the larger population with a small

rections were made for multiple comparisons in this

BSA (i.e., centers implanted the device only in small

study.

patients they thought would be most likely to succeed). The preoperative demographic, INTERMACS

CONCLUSIONS

profile, and end-organ laboratory do not suggest this is the case, but it remains possible. The limited

In a large, national registry, there was no difference in

number of small patients and differences in patient

post-VAD mortality in relation to the size of the pa-

characteristics make it difficult to assess the effect of

tient. Although there were small differences in spe-

size alone and may also confound the reported

cific adverse events, which require further study,

differences in adverse event rates while making

these differences did not affect survival, and thus

7

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Zafar et al.

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VADs in Patients With a BSA #1.5 m2

small size alone should not be a deterrent to CFLVAD implantation. These data should provide care providers reassurance to implant patients with a BSA of <1.5 m 2 if they meet other criteria for VAD support.

PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: CFLVADs are being placed in patients who are smaller

the

than the current size recommendations in the device

INTERMACS investigators, coordinators, and partici-

labeling. In this analysis of the INTERMACS registry,

pating institutions for the data they have provided for

we demonstrate that patients #1.5 m2 supported with

this registry.

CFLVADs have similar survival to larger patients.

ACKNOWLEDGMENTS The

authors

thank

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

Angela Lorts, The Heart Institute, MLC 2003, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229. E-mail: angela.

TRANSLATIONAL OUTLOOK: Further studies are needed to define the inflection point where small patient size adversely impacts survival in patients implanted with a CFLVAD.

[email protected].

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