correspondence
70 40
Devices with Confirmed Pump Thrombosis (%)
65
Devices with Confirmed Pump Thrombosis (%)
60 55 50 45 40
35 30 25
Before March 2011
15 10 5 0
35
March 2011 and after
20
0
20
12
18
24
30
23 —
12 —
Months since Implantation
30 25
6
No. at Risk Before March 2011 March 2011 and after
79 84
56 47
56 —
56 —
15 10 5 0 2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
Year of Implantation
Figure 1. Percentage of Devices with Confirmed Pump Thrombosis at 3 Months after HeartMate II Implantation. The data shown are based on 1058 devices implanted in 989 patients at four institutions. In the larger figure and the inset, the parametric estimates (solid lines) with corresponding 95% confidence intervals (dashed lines) are shown. The inset shows the occurrence of confirmed pump thrombosis among patients who received the HeartMate II at the University of Pennsylvania, stratified according to whether the date of implantation was before March 1, 2011, or on or after that date. Each symbol represents an event, with I bars indicating 95% confidence intervals.
four individual large referral centers for LVAD implantation show that since 2011 there has been an increased occurrence of pump thrombosis within the first 6 months after transplantation. The mechanisms behind this change in the occurrence and natural history of pump thrombosis remain unknown. J. Eduardo Rame, M.D. Pavan Atluri, M.D. Michael A. Acker, M.D. Hospital of the University of Pennsylvania Philadelphia, PA [email protected]
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. 1. Starling RC, Moazami N, Silvestry SC, et al. Unexpected
abrupt increase in left ventricular assist device thrombosis. N Engl J Med 2014;370:33-40. 2. Kirklin JK, Naftel DC, Kormos RL, et al. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device. J Heart Lung Transplant 2014;33:12-22. 3. Najjar SS, Slaughter MS, Pagani FD, et al. An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial. J Heart Lung Transplant 2014;33:23-34. DOI: 10.1056/NEJMc1402425
A Different Perspective on Thrombosis and the HeartMate II To the Editor: Concern regarding pump throm- been heightened after two recent articles docubosis in patients who have received the Heart- mented an increased incidence of pump thromMate II left ventricular assist device (LVAD) has bosis beginning in 2011.1,2 Although causality
n engl j med 370;15 nejm.org april 10, 2014
1467
The New England Journal of Medicine Downloaded from nejm.org at NEW YORK MEDICAL COLLEGE on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
The
n e w e ng l a n d j o u r na l
Devices with Confirmed Pump Thrombosis (%)
1 Yr
10 8 6 4 2 3 Mo
John M. Stulak, M.D.
20 04 20 05 20 06 20 07 20 08 20 09 20 10 20 11 20 12 20 13
0
Mayo Clinic College of Medicine Rochester, MN
Year of Implantation
[email protected]
Simon Maltais, M.D., Ph.D.
Figure 1. Percentage of Devices with Confirmed Pump Thrombosis at Institutions in the Mechanical Circulatory Support Research Network at 3 Months and 1 Year after HeartMate II Implantation. Aggregate data are from the Mayo Clinic in Rochester, Minnesota, the University of Michigan, and the Vanderbilt Heart and Vascular Institute. After a peak in the incidence of pump thrombosis in 2012, a significant decrease was observed in 2013.
Vanderbilt Heart and Vascular Institute Nashville, TN Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. 1. Starling RC, Moazami N, Silvestry SC, et al. Unexpected
cannot be fully ascertained with the current reported data, it is interesting to note that the issue of pump thrombosis arose after reports of a lower thromboembolic risk associated with the HeartMate II LVAD and adoption of less intense anticoagulation strategies (international normalized ratio, 1.5 to 2.0) beginning in 2009,3 including the safe nonuse of perioperative intravenous heparin as an anticoagulation bridge.4 We performed an individual-center and aggregate analysis of confirmed pump thrombosis (as defined by recent studies1,2) involving 516 patients who received the HeartMate II at the three institutions in the Mechanical Circulatory Support Research Network (254 at the University of Michigan, 205 at the Mayo Clinic in Rochester, Minnesota, and 57 at the Vanderbilt Heart and Vascular Institute). Our findings confirm a significant increase in the rate of pump thrombosis among patients who received the HeartMate II LVAD, with a peak in 2012, similar to that reported by the investigators at the Interagency Registry for Mechanically Assisted Circulatory Support. However, in 2013, we observed a different trajectory, with a subsequent decrease back to prior reported postmarketing levels5
1468
n engl j med 370;15
m e dic i n e
(Fig. 1). Although recent findings of increased pump thrombosis (beginning in 2011) may be temporally related to past reports on the relative safety of lower anticoagulation strategies (beginning in 2009), the issue of pump thrombosis is complex and undoubtedly multifactorial in nature. The disparate observations described herein underscore the complexity of this issue and the need for more granular analyses from collaborative efforts.
14 12
of
abrupt increase in left ventricular assist device thrombosis. N Engl J Med 2014;370:33-40. 2. Kirklin JK, Naftel DC, Kormos RL, et al. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device. J Heart Lung Transplant 2014;33:12-22. 3. Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant 2010;29:Suppl: S1-S39. 4. Slaughter MS, Naka Y, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant 2010;29:616-24. 5. Starling RC, Naka Y, Boyle AJ, et al. Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol 2011;57:1890-8. DOI: 10.1056/NEJMc1402278 Copyright © 2014 Massachusetts Medical Society.
instrUCtiOns FOr letters tO the editOr
Letters to the Editor are considered for publication, subject to editing and abridgment, provided they do not contain material that has been submitted or published elsewhere. Please note the following: • Letters in reference to a Journal article must not exceed 175 words (excluding references) and must be received within 3 weeks after publication of the article. • Letters not related to a Journal article must not exceed 400 words. • A letter can have no more than five references and one figure or table. • A letter can be signed by no more than three authors.
nejm.org
april 10, 2014
The New England Journal of Medicine Downloaded from nejm.org at NEW YORK MEDICAL COLLEGE on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
70 40
Devices with Confirmed Pump Thrombosis (%)
65
Devices with Confirmed Pump Thrombosis (%)
60 55 50 45 40
35 30 25
Before March 2011
15 10 5 0
35
March 2011 and after
20
0
20
12
18
24
30
23 —
12 —
Months since Implantation
30 25
6
No. at Risk Before March 2011 March 2011 and after
79 84
56 47
56 —
56 —
15 10 5 0 2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
Year of Implantation
Figure 1. Percentage of Devices with Confirmed Pump Thrombosis at 3 Months after HeartMate II Implantation. The data shown are based on 1058 devices implanted in 989 patients at four institutions. In the larger figure and the inset, the parametric estimates (solid lines) with corresponding 95% confidence intervals (dashed lines) are shown. The inset shows the occurrence of confirmed pump thrombosis among patients who received the HeartMate II at the University of Pennsylvania, stratified according to whether the date of implantation was before March 1, 2011, or on or after that date. Each symbol represents an event, with I bars indicating 95% confidence intervals.
four individual large referral centers for LVAD implantation show that since 2011 there has been an increased occurrence of pump thrombosis within the first 6 months after transplantation. The mechanisms behind this change in the occurrence and natural history of pump thrombosis remain unknown. J. Eduardo Rame, M.D. Pavan Atluri, M.D. Michael A. Acker, M.D. Hospital of the University of Pennsylvania Philadelphia, PA [email protected]
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. 1. Starling RC, Moazami N, Silvestry SC, et al. Unexpected
abrupt increase in left ventricular assist device thrombosis. N Engl J Med 2014;370:33-40. 2. Kirklin JK, Naftel DC, Kormos RL, et al. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device. J Heart Lung Transplant 2014;33:12-22. 3. Najjar SS, Slaughter MS, Pagani FD, et al. An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial. J Heart Lung Transplant 2014;33:23-34. DOI: 10.1056/NEJMc1402425
A Different Perspective on Thrombosis and the HeartMate II To the Editor: Concern regarding pump throm- been heightened after two recent articles docubosis in patients who have received the Heart- mented an increased incidence of pump thromMate II left ventricular assist device (LVAD) has bosis beginning in 2011.1,2 Although causality
n engl j med 370;15 nejm.org april 10, 2014
1467
The New England Journal of Medicine Downloaded from nejm.org at NEW YORK MEDICAL COLLEGE on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
The
n e w e ng l a n d j o u r na l
Devices with Confirmed Pump Thrombosis (%)
1 Yr
10 8 6 4 2 3 Mo
John M. Stulak, M.D.
20 04 20 05 20 06 20 07 20 08 20 09 20 10 20 11 20 12 20 13
0
Mayo Clinic College of Medicine Rochester, MN
Year of Implantation
[email protected]
Simon Maltais, M.D., Ph.D.
Figure 1. Percentage of Devices with Confirmed Pump Thrombosis at Institutions in the Mechanical Circulatory Support Research Network at 3 Months and 1 Year after HeartMate II Implantation. Aggregate data are from the Mayo Clinic in Rochester, Minnesota, the University of Michigan, and the Vanderbilt Heart and Vascular Institute. After a peak in the incidence of pump thrombosis in 2012, a significant decrease was observed in 2013.
Vanderbilt Heart and Vascular Institute Nashville, TN Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. 1. Starling RC, Moazami N, Silvestry SC, et al. Unexpected
cannot be fully ascertained with the current reported data, it is interesting to note that the issue of pump thrombosis arose after reports of a lower thromboembolic risk associated with the HeartMate II LVAD and adoption of less intense anticoagulation strategies (international normalized ratio, 1.5 to 2.0) beginning in 2009,3 including the safe nonuse of perioperative intravenous heparin as an anticoagulation bridge.4 We performed an individual-center and aggregate analysis of confirmed pump thrombosis (as defined by recent studies1,2) involving 516 patients who received the HeartMate II at the three institutions in the Mechanical Circulatory Support Research Network (254 at the University of Michigan, 205 at the Mayo Clinic in Rochester, Minnesota, and 57 at the Vanderbilt Heart and Vascular Institute). Our findings confirm a significant increase in the rate of pump thrombosis among patients who received the HeartMate II LVAD, with a peak in 2012, similar to that reported by the investigators at the Interagency Registry for Mechanically Assisted Circulatory Support. However, in 2013, we observed a different trajectory, with a subsequent decrease back to prior reported postmarketing levels5
1468
n engl j med 370;15
m e dic i n e
(Fig. 1). Although recent findings of increased pump thrombosis (beginning in 2011) may be temporally related to past reports on the relative safety of lower anticoagulation strategies (beginning in 2009), the issue of pump thrombosis is complex and undoubtedly multifactorial in nature. The disparate observations described herein underscore the complexity of this issue and the need for more granular analyses from collaborative efforts.
14 12
of
abrupt increase in left ventricular assist device thrombosis. N Engl J Med 2014;370:33-40. 2. Kirklin JK, Naftel DC, Kormos RL, et al. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device. J Heart Lung Transplant 2014;33:12-22. 3. Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant 2010;29:Suppl: S1-S39. 4. Slaughter MS, Naka Y, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant 2010;29:616-24. 5. Starling RC, Naka Y, Boyle AJ, et al. Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol 2011;57:1890-8. DOI: 10.1056/NEJMc1402278 Copyright © 2014 Massachusetts Medical Society.
instrUCtiOns FOr letters tO the editOr
Letters to the Editor are considered for publication, subject to editing and abridgment, provided they do not contain material that has been submitted or published elsewhere. Please note the following: • Letters in reference to a Journal article must not exceed 175 words (excluding references) and must be received within 3 weeks after publication of the article. • Letters not related to a Journal article must not exceed 400 words. • A letter can have no more than five references and one figure or table. • A letter can be signed by no more than three authors.
nejm.org
april 10, 2014
The New England Journal of Medicine Downloaded from nejm.org at NEW YORK MEDICAL COLLEGE on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
