The
n e w e ng l a n d j o u r na l
INR after Implantation
3 No confirmed pump thrombosis Confirmed pump thrombosis
1 0
0
2
4
6
8
10
12
Months after Implantation
INR after Implantation
March 1, 2011, and After
Randall C. Starling, M.D., M.P.H. Eugene H. Blackstone, M.D. Nicholas G. Smedira, M.D.
3 Confirmed pump thrombosis 2
0
Cleveland Clinic Cleveland, OH [email protected]
No confirmed pump thrombosis
1
0
2
4
m e dic i n e
changing, but we agree that it should be monitored and reported. Goldstein et al. summarize the key findings reported in our article and noted, as we have, that pump thrombosis is a complex, multifactorial condition. Our ongoing investigation to identify key factors contributing to pump thrombosis will include the important variables they have identified. We agree that routine monitoring of LDH after LVAD implantation is a valuable clinical biomarker to identify pump thrombosis.
Before March 1, 2011
2
of
6
8
10
Since publication of their article, the authors report no further potential conflict of interest.
12
Months after Implantation
1. Kirklin JK, Naftel DC, Kormos RL, et al. Interagency Regis-
try 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.
Figure 1. Measurements of the International Normalized Ratio (INR) after HeartMate II Implantation at the Cleveland Clinic before and after March 2011.
DOI: 10.1056/NEJMc1401768
Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis To the Editor: Implantation of a left ventricular assist device (LVAD) remains a standard of care for patients with advanced heart failure who may derive a survival benefit with enhanced quality of life. An increased incidence of pump thrombosis has been reported, with urgent consideration of bailout cardiac transplantation, device exchange, or high-risk thrombolytic therapy. An important observation has been reported in two recent articles: Starling et al. (Jan. 2 issue)1 summarize the rate of device thrombosis among 837 patients across three implantation centers, and Kirklin et al.2 describe data reported to the Interagency Registry for Mechanically Assisted Circulatory Support on the rate of device thrombosis among 6910 patients. Both articles identified a temporal shift in the rate of LVAD thrombosis marked by an increase in this event rate beginning in 2011, without a specific cause or unifying mechanism. The development of hemolysis, with an abrupt and sustained increase in serum lactate dehydro1466
n engl j med 370;15
genase levels, is uniformly an associated antecedent event, but causal factors linking these observations and best treatment options for pump thrombosis — which occur in both axial-flow and centrifugal-flow LVADs — are lacking.3 The Mechanical Circulatory Support Program at the University of Pennsylvania has extensive, ongoing experience with implantation of continuousflow devices, including the HeartMate II LVAD. From November 1, 2005, through October 17, 2013, a total of 163 HeartMate II LVADs were implanted. A temporal change with an increased occurrence of confirmed LVAD thrombosis was identified after an internal analysis and formal discussion with the manufacturer. A collaboration formed in October 2013 with the Cleveland Clinic, Washington University, and Duke University Medical Center has confirmed our initial analysis, and we now report the fully analyzed and integrated composite data on 1058 device implants in 989 patients (Fig. 1). The data across
nejm.org
april 10, 2014
The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF GEORGIA on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
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
The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF GEORGIA on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
1467
n e w e ng l a n d j o u r na l
INR after Implantation
3 No confirmed pump thrombosis Confirmed pump thrombosis
1 0
0
2
4
6
8
10
12
Months after Implantation
INR after Implantation
March 1, 2011, and After
Randall C. Starling, M.D., M.P.H. Eugene H. Blackstone, M.D. Nicholas G. Smedira, M.D.
3 Confirmed pump thrombosis 2
0
Cleveland Clinic Cleveland, OH [email protected]
No confirmed pump thrombosis
1
0
2
4
m e dic i n e
changing, but we agree that it should be monitored and reported. Goldstein et al. summarize the key findings reported in our article and noted, as we have, that pump thrombosis is a complex, multifactorial condition. Our ongoing investigation to identify key factors contributing to pump thrombosis will include the important variables they have identified. We agree that routine monitoring of LDH after LVAD implantation is a valuable clinical biomarker to identify pump thrombosis.
Before March 1, 2011
2
of
6
8
10
Since publication of their article, the authors report no further potential conflict of interest.
12
Months after Implantation
1. Kirklin JK, Naftel DC, Kormos RL, et al. Interagency Regis-
try 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.
Figure 1. Measurements of the International Normalized Ratio (INR) after HeartMate II Implantation at the Cleveland Clinic before and after March 2011.
DOI: 10.1056/NEJMc1401768
Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis To the Editor: Implantation of a left ventricular assist device (LVAD) remains a standard of care for patients with advanced heart failure who may derive a survival benefit with enhanced quality of life. An increased incidence of pump thrombosis has been reported, with urgent consideration of bailout cardiac transplantation, device exchange, or high-risk thrombolytic therapy. An important observation has been reported in two recent articles: Starling et al. (Jan. 2 issue)1 summarize the rate of device thrombosis among 837 patients across three implantation centers, and Kirklin et al.2 describe data reported to the Interagency Registry for Mechanically Assisted Circulatory Support on the rate of device thrombosis among 6910 patients. Both articles identified a temporal shift in the rate of LVAD thrombosis marked by an increase in this event rate beginning in 2011, without a specific cause or unifying mechanism. The development of hemolysis, with an abrupt and sustained increase in serum lactate dehydro1466
n engl j med 370;15
genase levels, is uniformly an associated antecedent event, but causal factors linking these observations and best treatment options for pump thrombosis — which occur in both axial-flow and centrifugal-flow LVADs — are lacking.3 The Mechanical Circulatory Support Program at the University of Pennsylvania has extensive, ongoing experience with implantation of continuousflow devices, including the HeartMate II LVAD. From November 1, 2005, through October 17, 2013, a total of 163 HeartMate II LVADs were implanted. A temporal change with an increased occurrence of confirmed LVAD thrombosis was identified after an internal analysis and formal discussion with the manufacturer. A collaboration formed in October 2013 with the Cleveland Clinic, Washington University, and Duke University Medical Center has confirmed our initial analysis, and we now report the fully analyzed and integrated composite data on 1058 device implants in 989 patients (Fig. 1). The data across
nejm.org
april 10, 2014
The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF GEORGIA on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
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
The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF GEORGIA on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
1467
