Gastrointestinal Bleeding: Diagnosis and Management
Strategies
Paolo C. Colombo, M.D., F.A.C.C.Sudhir Choudhrie Professor of Cardiology
Director, Center for Advanced Cardiac Care: Heart Failure, MCS & Transplant
Division of CardiologyColumbia University Medical Center
Presenter Disclosure Information
Paolo Colombo, MD
The following relationships exist related to this presentation:
Research Grant: Abbott Consultant: Abbott (no honoraria)
Morgan / Brewer JHLT 2012 Axelrad/Yuzefpolskaya JHLT 2018
GIB does NOT kill CF-LVAD recepients
Goldstein / Slaghter JACC-HF 2013
Most common cause of morbidity and hospital readmission
Incidence is 25%
Blood product requirement (sensitization) - BTT
Reduced QOL
The scope of the problem
Risk factors for GIB in CF-LVADs
Older age Female gender Ischemic cardiomyopathy Prior h/o GIB Right ventricular
dysfunction Destination therapy Low Pulsatility Index Dual-antiplatelet therapy Elevated INR
CF-LVADs
Joy et al AJC 2016
GIB is greater in the era of CF-LVADs than in the era of pulsatile-flow LVADs
GI bleed in LVAD patients is more common than similarly anticoagulated controls with valvular replacement
Schrode /Sauer CGH 2014
10,000 rpmADAMTS13
+
Hematologic factors
Antithrombotic therapy
+Acquires vW deficiency:
Anatomic factors
Angiodysplasia
Pathogenesis of GIB during CF-LVAD support
all pts, all CF-LVADs Less with:
Lower speed HM3
Ischemia / low pulsatility Inflammation
Altered angiogenesis (angiodysplasia)
45-65% of GIB
http://www.gastrointestinalatlas.com/english/hereditary_hemorrhagic_telangi.html
Tabit / Liao Circulation 2016 & JHLT 2018
TNF-alpha is a central regulator of altered angiogenesis in CF-LVADs
1) Is a focal or diffuse GI processand 2) is it a systemic process?
+ TGF- + HIF-1
Kang / Bartoli Circ Res 2017
Angiodysplasia is a diffuse process in the GI track of CF-LVADs
Humans LVAD; N=4 Control; N=4Cows LVAD; N=2 Control; N=4Sheeps LVAD; N=3 Control; N=3
Autopsy samples mid-jejunum(not AVM sites)
Patel / Jorde JACC-HF 2017
Angiodysplasia is a systemic process in HF and LVAD
Antithrombotic therapy
+Acquired vW deficiency
=GIB
1st Hit 2nd Hit
Anticoagulation
What shall we do with warfarin? Try to continue
Nassif / Gage Circ Heart Fail 2016Scilla
Cariddi
ASA
Probably safe to stop
What shall we do with warfarin? Probably safe to stop
PREVENT II TRIALPREVENTion of Non-Surgical Bleeding by Management of
HeartMate II Patients without Antiplatelet Therapy
Sieg/Jennings Pharmacotherapy 2017
Houston BA JHLT 2017
Vasoconstriction Increase platelet function Decrease angiogenesis
LVAD since 2004
Sieg/Jennings Pharmacotherapy 2017
Wever-Pinzon / Bader Circ Heart Fail 2013
Attenuated pulsatility (low PI, high speed) contributes to GIB
Muthiah / Hayward JHLT 2016
1. Will decrease CF-LVAD speed reduce GIB? Probably (less avWd, more pulsatility)2. Should we decrease the speed? NO
(PREVENT recommendations speed >9000 rpm)
0.152.00
c
0.20
2000
time [s]
rotor speed [rpm]
HM3 Artificial Pulse
What the hemocompatiblity properties of all the drugs we are using in CF-LVAds?
Sildenafil (platelet dysfunction) Digoxin (anti-angiogenesis / HIF-1) BBs (carvedilol vs. metoprolol) Statins (anti-angiogenesis at high dose) SSRIs (platelet dysfunction)
Large clinical trials MOMENTUM 3 / ENDURANCEMulticenter RCT focusing on medical therapy (eg PREVENT II)
BleedingClotting
Mehra M EHJ 2017
The scope of the problem
http://www.gastrointestinalatlas.com/english/hereditary_hemorrhagic_telangi.html
CUMC HF/GI TeamMelana Yuzefpolskaya, MD
Jordan Axelrad, MD
Tamas Gonda, MD
Alberto Pinsino, MDDew Thanataveerat, MPHPauline Trinh, MPH
CUMC Experience: Predictors of GIBin 428 CF-LVAD recipients
LVAD patients without GIB (n=341; 79.7%)
LVAD patients with GIB (n=87; 20.3%)
p-value
Age at LVAD implantation
55.3 +/- 13.6 62 +/- 11.5
CUMC Experience: Index GIBTotal (n=87)
Median days from LVAD to GIB 55Bleeding Presentation
UGIB (melena, hematemesis, coffee-ground emesis)LGIB (hematochezia)Occult (hemepositive stool, iron deficiency anemia)
30 (34.5%)19 (21.8%)38 (43.7%)
Baseline medications prior to GIBAnticoagulationAntiplatelet therapy
None Aspirin 81mgAspirin 81mg with Dipyridamole
Proton pump inhibitor
87 (100%)
4 (4.6%)77 (88.5%)
6 (6.9%)63 (71.3%)
Median laboratory values at GIBINR Hemoglobin Change in hemoglobin Platelets
2.27.32.4213
Product requirements Packed red blood cells
Median number of pRBCVitamin KFresh frozen plasma
72 (82.8%)3
9 (10.3%)16 (18.4%)
Median LOS (days) 12
CUMC Experience: Endoscopic and therapeutic yields by GIB presentation
UGIB (n=27, 34.5%)
Number Diagnostic Yield
Therapeutic Yield
EGD 26 11 (42.3%) 6 (23.1%)Colonoscopy 16 2 (12.5%) 0Enteroscopy 4 4 (100%) 3 (75%)Capsule 7 5 (71.4%) -Total 53 22 (41.5%) 9 (19.6%)
Axelrad / Yuzefpolskaya JHLT 2018
CUMC Experience: Endoscopic and therapeutic yields by GIB presentation
LGIB (n=13, 21.8%)
Number Diagnostic Yield
Therapeutic Yield
EGD 8 1 (12.5%) 0Colonoscopy 15 9 (60%) 3 (20%)Enteroscopy 0 0 0Capsule 0 0 -Total 23 10 (43.5%) 3 (13%)
Axelrad / Yuzefpolskaya JHLT 2018
CUMC Experience: Endoscopic and therapeutic yields by GIB presentation
OGIB (n=36, 43.7%)
Number Diagnostic Yield
Therapeutic Yield
EGD 36 13 (36.1%) 8 (22.2%)Colonoscopy 25 3 (12%) 3 (12%)Enteroscopy 3 1 (33.3%) 1 (33.3%)Capsule 7 0 -Total 71 15 (21.1%) 12 (18.8%)
Axelrad / Yuzefpolskaya JHLT 2018
CUMC Experience: Endoscopic evaluation
Total locations identified: 49
Esophagus: 0
Stomach: 19/49(38.8%)
Duodenum: 9/49(18.4%)
Jejunum/Ileum: 7/49 (14.3%)
Colon: 14/49 (28.6%)
Axelrad / Yuzefpolskaya JHLT 2018
Chart1
AVM
Erosion/friable mucosa
Other
PUD
Diverticular
Lesions
Erosions27%
Hemorrhoid2%
21
12
4
5
3
Sheet1
Lesions
AVM21
Erosion/friable mucosa12
Other4
PUD5
Diverticular3
CUMC Experience: Endoscopic evaluationTotal (n=87)
Endoscopic evaluation 79 (90.8%)Endoscopic diagnosis 44/79 (50.6%)Endoscopic intervention 23/79 (29.1%)Rebleed within 6 months 43 (49.4%)
Total n= 79 to endoscopyProcedure # Diagnostic
YieldEndoscopic Intervention
EGD 70 25 (35.7%) 14 (20%)Colonoscopy 56 14 (25%) 6 (10.7%)Enteroscopy 7 5 (71.4%) 4 (57.1%)Capsule 14 5 (35.7%) -Total 147 49 (33.3%) 24 (16.3%)
Average 1.9 procedures per patient
Multiple lesions (26, 59.1%)
Axelrad / Yuzefpolskaya JHLT 2018
Predictors of recurrent GIBLVAD patients with one GIB
(n=44)
LVAD patients with recurrent
GIB (n=43)
Hazards Ratio p-value
Product requirements Packed red blood cells
Median number Vitamin KFresh frozen plasma
33 (75%)2 (0.5-4.0)3 (6.8%)8 (18.2%)
39 (90.7%)3 (2-7)6 (14%)
8 (18.6%)
2.51 [0.9, 7.05]1.05 [1.01, 1.09]2.24 [0.92, 5.47]1.22 [0.56, 2.63]
0.08010.00730.07520.6202
Endoscopic evaluation of index GIB
Source identified Location
None Upper GI tractLower GI tractUpper and lower GI tract
Type of lesionAVMErosionsOther
Intervention performed
18 (40.9%)
26 (59.1%)10 (22.7%)
8 (18.2%)0
936
9 (20.5%)
26 (60.5%)
17 (39.5%)20 (46.5%)
4 (9.3%)2 (4.7%)
1296
14 (53.8%)
1.75 [0.95, 3.24]
Reference2.82 [1.44, 5.52]
0.7 [0.24, 2.1]1.08 [0.25, 4.78]
Reference1.64 [0.68, 3.96]0.51 [0.18, 1.48]
1.92 [1.01, 3.66]
0.0747
0.00250.52630.9147
0.27130.21150.0480
Risk for re-bleed: Endoscopic intervention
Log rank p=0.0441
Dakik HK/Wild DM Dig Dis Sci2016 (Duke):
78 pts (30%) had 158 GIBs
Only risk factor for re-bleeding were:
Detection of a bleeding source (P=0.003)
Intervention during the index examination (p=0.013)
Axelrad / Yuzefpolskaya JHLT 2018
Endoscopic therapy seems to mainly identify patients at the highest risk for recurrent GIB, representing a marker for more extensive disease, and does not address the root cause of this problem.
Overcoming Futility?
A single, treatable source of bleeding is rarely identified in LVAD recipients
Endoscopic therapy does not appear to reduce the incidence of recurrent GIB
Management guidelines are significantly limited
Proposed AlgorithmUPPER GIBMelena, coffee-ground emesis, hematemesis
LOWER GIBHematochezia
OCCULT GIBHemepositive brown stool, iron deficiency
anemia
Push Enteroscopy Colonoscopy Initial medical management
Additional endoscopic evaluation in cases of: Hemodynamic instability despite administration of blood
products Persistent GIB despite withholding or after resumption of
lower-dose antithrombotic treatment Age-appropriate colon cancer screening
Case- 60yo M, Conventional management
6/17 7/6/17 7/7/17 7/8/17 7/9/17 7/11/17 7/14/17 7/16/17
ICMHMII LVADimplanted as DT
Developed MelenaAdmitted
GI called
Hgb 1.5 units below baselineAC HeldPPI gtt initiatedTransfused 2 units pRBCNPO
EGD performed without source
Hgb continues to decreaseTransfused 4 units pRBCPreps for colonoscopyNPO
Colonoscopyperformedwithout source
Capsuleendoscopyperformed
Preps for capsuleNPOMelena resolves
Capsule read with nonbleeding jejunal AVMsNPONo further melena
Push enteroscopy Performed with APC of nonbleeding jejunal AVMs
AC restartedDischarged
LOS: 11 days, pRBC: 6 units
Case- 60yo M, management per new algorithm
6/17 7/6/17 7/7/17 7/8/17 7/10/17
ICMHMII LVADimplanted as DT
Developed MelenaAdmitted
GI called Push enteroscopy Performed with APC of oozing jejunal AVMs
Hgb stabilizesMelena resolves
AC restartedDischarged
LOS: 5 days, pRBC: 2 units
Potential Benefits
Conventional management 87 initial admissions and 147 endoscopies: $2,230,609
Proposed algorithm Projected 66 endoscopies, a reduction by nearly 45% Assuming that each reduction in endoscopic procedure would
translate into one less day spent in the hospital, the overall estimated cost would be $1,449,414, representing a 35% savings
Axelrad / Yuzefpolskaya JHLT 2018
Conclusions
GIB is frequent 25%, but does not impact survival
Pathogenesis: Hematologic (antithrombotic therapy and vWF deficiency) + structural abnormalities (AVMs)
Medical management: Stop ASA, continue AC, ACEI and Octreotide (Thalidomide)
Endoscopic management: low diagnostic and therapeutic yield
We propose an algorithm that may significantly reduce the number of low-yield endoscopies, LOS and costs -Prospective Results (ISHLT 2018)
Thank you!
Gastrointestinal Bleeding: Diagnosis and Management StrategiesSlide Number 2Slide Number 3The scope of the problemRisk factors for GIB in CF-LVADsSlide Number 6Slide Number 7Slide Number 8Slide Number 9Slide Number 10AnticoagulationSlide Number 12Slide Number 13Slide Number 14Slide Number 15Slide Number 16Slide Number 17The scope of the problemCUMC HF/GI TeamCUMC Experience: Predictors of GIBin 428 CF-LVAD recipientsCUMC Experience: Index GIBCUMC Experience: Endoscopic and therapeutic yields by GIB presentationCUMC Experience: Endoscopic and therapeutic yields by GIB presentationCUMC Experience: Endoscopic and therapeutic yields by GIB presentationCUMC Experience: Endoscopic evaluationCUMC Experience: Endoscopic evaluationPredictors of recurrent GIBRisk for re-bleed: Endoscopic interventionOvercoming Futility? Proposed AlgorithmCase- 60yo M, Conventional managementPotential BenefitsConclusionsSlide Number 34
