Outcomes of mechanical circulatory support in HIV infected patients from the INTERMACS registry

1
Outcomes of mechanical circulatory support in HIV
infected patients from the INTERMACS registry

• Salpy V. Pamboukian MD MSPH
• Intermacs Annual Meeting
• May 15-16th, 2015

2
Background and Purpose

• There is limited published data on the outcomes
  of HIV infected patients requiring mechanical
  circulatory support (MCS)
• Prevalence of 1.2 million cases in the U.S. (CDC,
  2011)
• With cART therapy, HIV has been converted into a
  chronic disease
• High prevalence of cardiac risk factors ? smoking
  60-70
• 6.5 of HIV-related mortality is related to CV
  disease (1)
• Prevalence of LV dysfunction was 18 in one large
  echo series (2)
• The purpose of our study was to analyze outcomes
  in HIV infected patients with MCS enrolled in the
  INTERMACS registry

1. Causes of death in HIV-1-infected patients
treated with antiretroviral therapy, 19962006
collaborative analysis of 13 HIV cohort
studies Clin Infect Dis, 50 (2010), pp. 13871396
2. Mondy KE et al. Clin Infect Dis
20115237886.
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Methods

• INTERMACS enrolled 14,039 primary prospective
  patients between June 23, 2006 and March 31,
  2015, of these 28 were identified with a
  pre-implant HIV positive status. Three patients
  with pulsatile flow devices were excluded from
  further analysis.
• Baseline characteristics (age, race, gender,
  device strategy, patient profile, time since
  cardiac diagnosis, and etiology) were compared
  for patients receiving continuous flow LVADs with
  HIV (n25) and without HIV (n12,351). P-values
  were calculated using Fishers exact test or the
  Wilcoxon rank sum test.
• The difference in survival on a device for
  patients receiving continuous flow LVADs with HIV
  (n25) and without HIV (12,351) was analyzed
  using Kaplan-Meier survival curves using time to
  death as the event and censoring at transplant or
  ventricular recovery (device removed or turned
  off). The p-value was calculated using the
  log-rank test.
• Competing outcome methodology was used to
  estimate the time related percentage of patients
  receiving continuous flow LVADs with HIV that
  would be alive on a device, deceased, transplant,
  and recovered.
• Adverse event rates and infection rates by
  location were calculated by totaling the number
  of specific events observed in an early period (3
  months post implant or earlier) and late period
  (after 3 months post implant).

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Distribution of Pre-implant HIV Status for
Primary Prospective Patients by Device Type, Flow
Type
Cohort Selection
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Patients Characteristics by HIV Status
Pre-Implant Characteristics Pre-Implant Characteristics Pre-Implant Characteristics   HIV (n25) No HIV (n 12,351) p-value
AGE, median (IQR) AGE, median (IQR) 52 (41-60) 59 (50-66) 0.02
RACE
African American African American 14 (56.0) 2847 (23.1) 0.0005
White 10 (40.0) 8473 (68.6)
Other/Undisclosed Other/Undisclosed Other/Undisclosed 1 (4.0) 1031 (8.3)
GENDER 1.00
Female 5 (20.0) 2627 (21.3)
Male 20 (80.0) 9721 (78.7)
Unspecified Unspecified 0 (0.0) 3 ( 0.02)
DEVICE STRATEGY DEVICE STRATEGY 0.02
Bridge to Transplant - Listed (BTT) Bridge to Transplant - Listed (BTT) Bridge to Transplant - Listed (BTT) Bridge to Transplant - Listed (BTT) 4 (16.7) 3398 (27.5)
Bridge to Candidacy (BTC) Bridge to Candidacy (BTC) Bridge to Candidacy (BTC) 3 (16.7) 4062(32.9)
Destination Therapy (DT) Destination Therapy (DT) Destination Therapy (DT) 18 (61.1) 4800(38.9)
Bridge to Recovery (BTR) Bridge to Recovery (BTR) Bridge to Recovery (BTR) 0 (0.0) 49(0.4)
Other 0(0.0) 42(0.3)
PATIENT PROFILE PATIENT PROFILE 0.52
1 Critical Cardio Shock 1 Critical Cardio Shock 1 Critical Cardio Shock 3 ( 13.0) 1727 (14.1)
2 Progressive Decline 2 Progressive Decline 2 Progressive Decline 6 (26.1)) 4578 (37.4)
3 Stable but Inotrope dependent 3 Stable but Inotrope dependent 3 Stable but Inotrope dependent 3 Stable but Inotrope dependent 7 (30.4) 3686 (30.1)
4 Resting Symptoms 4 Resting Symptoms 4 Resting Symptoms 5 (21.7) 1700 (13.9)
5 Exertion intolerant 5 Exertion intolerant 5 Exertion intolerant 2 (8.7) 334(2.7)
6 Exertion limited 6 Exertion limited 0(0.0) 142(1.2)
7 Advanced NYHA Class 3 7 Advanced NYHA Class 3 7 Advanced NYHA Class 3 0(0.0) 78 (0.6)
Missing/Unknown Missing/Unknown Missing/Unknown   2 106  
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Patients Characteristics by HIV Status
(Continued)
Pre-Implant Characteristics Pre-Implant Characteristics Pre-Implant Characteristics Pre-Implant Characteristics             HIV (n25) No HIV  
Pre-Implant Characteristics Pre-Implant Characteristics Pre-Implant Characteristics Pre-Implant Characteristics             HIV (n25) (n 12,351) p-value
IMPLANT DATE IMPLANT DATE                 0.94
2006 0 (0.0) 1 ( 0.0)
2007 0 (0.0) 0 (0.0)
2008 0 (0.0) 440 (3.6)
2009 1 ( 4.0) 827 ( 9.1)
2010 3 (12.0) 1527 (16.8)
2011 2 (11.1) 1789 (19.7)
2012 6 (33.3) 2164 (23.7)
2013 6 (33.3) 2564 (25.9)
2014 6 (24.0) 2493(20.2)
2015 1(4.0) 549(4.4)
PRIMARY DIAGNOSIS PRIMARY DIAGNOSIS PRIMARY DIAGNOSIS 0.34
Non-Ischemic Heart Disease Non-Ischemic Heart Disease Non-Ischemic Heart Disease Non-Ischemic Heart Disease 16 (64.0) 6194 (50.1)
Ischemic Heart Disease Ischemic Heart Disease Ischemic Heart Disease 8(32.0) 5763 (46.7)
Other 1(4.0) 394(3.2)
FOLLOW-UP TIME (months), median (IRQ) FOLLOW-UP TIME (months), median (IRQ) FOLLOW-UP TIME (months), median (IRQ) FOLLOW-UP TIME (months), median (IRQ) FOLLOW-UP TIME (months), median (IRQ)           13 (6-18) 10 (4-22) 0.87
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Selected Pre-Implant Conditions by HIV Status
Concerns no HIV     HIV      
  N Yes N Yes p-value
History of Smoking 6926 2072 29.92 19 10 52.60 0.03
Currently Smoking 6926 302 4.40 19 3 15.80 0.02
Severe Depression 6926 188 2.70 19 1 5.30 0.5
Other Major Psychiatric Diagnosis 6926 121 1.70 19 1 5.30 0.27
Other Co-Morbidity 6926 529 7.60 19 3 15.80 0.18
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Causes of Death of HIV Infected Patients
Time Supported (months) Implant Year Primary Cause of Death Discharge Status Primary Cause of Death Other Specify Primary Cause of Death Cancer Other Specify Specify Support
0.1 2012 Circulatory Other, Specify Died during the implant hospitalization Cardio-pulmonary arrest    
0.6 2012 Multisystem Organ Failure (MSOF) Died during the implant hospitalization      
3.2 2012 Withdrawal of Support, specify Died during the implant hospitalization     withdrawal of ventilator and LVAD
12.0 2010 Other Cancer Discharged alive with a device in place   Acute myeloblastic leukemia  
12.3 2013 Multisystem Organ Failure (MSOF) Discharged alive with a device in place      
17.1 2011 Multisystem Organ Failure (MSOF) Discharged alive with a device in place      
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Comparison of HIV Infected Patients Died vs
Alive (as of 03/31/2015)
Pre - Implant Characteristic Pre - Implant Characteristic Pre - Implant Characteristic Died(n6) Alive(n19) p
AGE, median (IQR) AGE, median (IQR) AGE, median (IQR) 59 (49-62) 49 (37-54) 0.2
RACE RACE RACE 0.75
African American 4(66.7) 10 (52.6)
White 2(33.3) 8(42.1)
Other, Unknown, Undisclosed 0(0.0) 1(5.3)
GENDER GENDER GENDER 0.81
Female 1 (16.7) 4 (21.1)
Male 5 (83.3) 15 (78.9)
DEVICE STRATEGY DEVICE STRATEGY DEVICE STRATEGY 0.22
Bridge to Transplant - Listed 4 (21.1)
Bridge to Candidacy 0 (0.0) 3 (15.8)
Destination Therapy 6 (100) 12( 63.2)
PATIENT PROFILE PATIENT PROFILE PATIENT PROFILE 0.65
1 Critical Cardio Shock 3 (17.6)
2 Progressive Decline 2 (33.3) 4 (23.5)
3 Stable but Inotrope dependent 2 (33.3) 5 (29.4)
4 Resting Symptoms 2 (33.3) 3 (17.6)
5 Exertion Intolerant 5 Exertion Intolerant 5 Exertion Intolerant 5 Exertion Intolerant 2 (11.8)
Unknown/Missing Unknown/Missing Unknown/Missing Unknown/Missing 2 (. )
TIME SINCE FIRST CARDIAC DIAGNOSIS TIME SINCE FIRST CARDIAC DIAGNOSIS TIME SINCE FIRST CARDIAC DIAGNOSIS TIME SINCE FIRST CARDIAC DIAGNOSIS 0.84
1 month - 1 year 1 (16.7) 4 (16.7)
1 -2 Years 1 (5.3)
gt 2 years 5 (83.3) 13 (68.4)
Unknown Unknown Unknown 1 (5.3)
IMPLANT DATE IMPLANT DATE IMPLANT DATE 0.4
2009 1 ( 5.3)
2010 1 (16.7) 2 (10.5)
2011 1 (16.7) 1( 5.3)
2012 3 (50.0) 3 (15.8)
2013 1 (16.7) 5 (26.3)
2014 2014 2014 6 (31.6)
2015 2015 2015 1 (5.3)
PRIMARY DIAGNOSIS PRIMARY DIAGNOSIS PRIMARY DIAGNOSIS 0.84
Ischemic Heart Disease Ischemic Heart Disease 2 (33.3) 6 (31.6)
Non-Ischemic Heart Disease Non-Ischemic Heart Disease 4 (66.7) 12 (63.2)
  Other Other   1 ( 5.3)  
FOLLOW-UP TIME (months), median (IRQ) 7.6 (.59-12.3) 15.6 (7.9-23.9) FOLLOW-UP TIME (months), median (IRQ) 7.6 (.59-12.3) 15.6 (7.9-23.9) FOLLOW-UP TIME (months), median (IRQ) 7.6 (.59-12.3) 15.6 (7.9-23.9) FOLLOW-UP TIME (months), median (IRQ) 7.6 (.59-12.3) 15.6 (7.9-23.9) FOLLOW-UP TIME (months), median (IRQ) 7.6 (.59-12.3) 15.6 (7.9-23.9) .08
p-values fishers exact test, or wilcoxon rank sum p-values fishers exact test, or wilcoxon rank sum p-values fishers exact test, or wilcoxon rank sum p-values fishers exact test, or wilcoxon rank sum p-values fishers exact test, or wilcoxon rank sum
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Adverse Event Rates
Adverse Event Type   Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months)   Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months)
Adverse Event Type HIV HIV no HIV no HIV Rate Ratio Rate Ratio HIV HIV no HIV no HIV Rate Ratio Rate Ratio
Adverse Event Type Events (N) Rate Events (N) Rate Rate Ratio Rate Ratio Events (N) Rate Events (N) Rate Rate Ratio Rate Ratio
Arterial Non-CNS Thromboembolism 132 0.4 70 0.0
Bleeding 4 5.8 5861 17.4 0.3 16 4.9 5503 3.3 1.5
Cardiac Arrhythmia 9 13.1 3677 10.9 1.2 5 1.5 1740 1.0 1.5
Device Malfunction 3 4.4 899 2.7 1.6 5 1.5 2478 1.5 1.0
Hemolysis 226 0.7 659 0.4
Hepatic Dysfunction 436 1.3 349 0.21
Hypertension 154 0.5 355 0.2
Infection 13 19.0 5012 14.9 1.3 28 8.6 6574 4.0 2.2
Myocardial Infarction 42 0.12 47 0.03
Neurological Dysfunction 2 2.9 1344 4.0 0.7 10 3.1 2056 1.2 2.5
Other Serious Adverse Event 7 10.2 4260 12.6 0.8 12 3.7 3198 1.9
Pericardial Drainage 3 4.4 574 1.7 2.6 25 0.0
Psychiatric Episode 3 4.4 799 2.4 1.8 1 0.31 523 0.31 1.0
Rehospitalization 15 21.9 7206 21.4 1.0 66 20.3 26625 16.0 1.3
Renal Dysfunction 1 1.5 1235 3.7 0.4 3 0.9 774 0.5 2.0
Respiratory Failure 6 8.8 2375 7.0 1.2 4 1.2 826 0.5 2.5
Right Heart Failure 207 0.6 577 0.3
Venous Thromboembolism 544 1.6 108 0.07
Wound Dehiscence         171 0.5               51 0.03      
Rates are reported per 100 patient months Rates are reported per 100 patient months Rates are reported per 100 patient months
Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months
Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months
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Infection Rates by Location
Infection Location   Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months) Early Period (lt3 months)   Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months) Late Period (gt3 months)
Infection Location HIV HIV no HIV no HIV Rate Ratio Rate Ratio HIV HIV no HIV no HIV Rate Ratio Rate Ratio
Infection Location Events (N) Rate Events (N) Rate Rate Ratio Rate Ratio Events (N) Rate Events (N) Rate Rate Ratio Rate Ratio
GI 1 7.9 2 3.6 2.2 1 3.1
Line Sepsis 1 7.9 1 0.3
Other Specify 1 7.9 1 3.1 2 0.7 4.5
Positive Blood Cultures 1 7.9 2 3.6 2.2 5 15.4 3 1.0 15.0
Pulmonary 2 15.7 1 1.8 8.8 3 9.2 1 0.3 27.0
Pump/Related - Drive Line 1 7.9 3 9.2 6 2.0 4.5
Urinary Tract   2 15.7   1 1.8   8.8     3 9.2   1 0.3   27.0  
Rates are reported per 100 patient months Rates are reported per 100 patient months Rates are reported per 100 patient months
Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months Early Follow-up HIV 68.5 patient months, no HIV 33725.11 patient months
Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months Late Follow-up HIV325.3 patient months, no HIV 166137 patient months
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(No Transcript)
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Kaplan Meier Survival Estimates
Months after Device Implant no HIV HIV
1 95 92
3 91 92
6 87 88
12 81 88
24 70 68
36 59 68
48 48 68
60 41 .
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Competing Outcomes HIV Patients
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Competing Outcomes - No HIV Patients
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Limitations

• Information on CD4 counts, viral loads, drug
  regimens is lacking
• These patients were likely highly selected and
  may not be generalizable

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Inferences

• Although they were younger, HIV infected patients
  were implanted as destination therapy more
  frequently
• identified as having contraindications to
  transplantation, immunosuppression
• Analysis (25 HIV patients, June 2006 - June 2015)
  indicated similar survival in HIV infected
  patients after MCS
• After implantation, infectious complications were
  more frequent in HIV infected patients