Impella and Acute Kidney Injury: Implications
on Practice, Decision Making, and Integration
into Protocols
Michael P. Flaherty, M.D., Ph.D.
Director, Cardiac Catheterization Lab
Director, Adult Structural Heart Disease
Director, Research Interventional Cardiology
Heart Institute, Kentuckiana Medical Center
Overview
• Our data → Renal protection with Impella in HR-PCI
with reduced LVEF (≤35%)
• New data → Europe and cVAD
• Risk stratification → should there be an indication
for Impella in patients at high-risk for CKD?
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Objective
Does hemodynamic support from Impella during
HRPCI protect against acute kidney injury when
compared to the same revascularization strategy in
patients without hemodynamic support
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Design
Retrospective, control-matched study (2011-2014): Single-center
catheterization laboratory database
consecutive patients, high-risk cardiac procedures with Impella support with LV systolic
dysfunction
153 patients (Impella support)
38 Excluded
• 22 EP procedures, 9 CP insertions
• 7 either no PCI or EF>35%
115 patients
Elective/Urgent/Emergent PCI
•EF ≤35%.
115 patients
Elective/Urgent/Emergent PCI
•EF ≤35%.
Controls (data query)
Matched
• age, gender
• EF (range 10-35%), acuity of presentation
• Contrast load used
No IABP included
115 patients
Elective/Urgent/Emergent PCI
•EF ≤35%.
Controls (data query)
Matched
• age, gender
• EF (range 10-35%), acuity of presentation
• Contrast load used
No IABP included
115 patientsControls (data query)
Matched
• age, gender
• EF (range 10-35%), acuity of presentation
• Contrast load used
No IABP included
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Primary Outcome Measure
Primary outcome: defined as the development of acute kidney injury
(AKI) periprocedurally from insertion of the Impella 2.5 device/sheath
up to 72h; all Impella inserted pre-PCI
Classification of AKI, AKIN criteria
• stage 1, ≥0.3 mg/dl absolute or 1.5 to 2.0-fold relative increase in
serum creatinine
• stage 2, >2- to 3 fold increase in serum creatinine
• stage 3, >3-fold increase in serum creatinine or serum creatinine >4.0
mg/dl with an acute increase of >0.5 mg/dl).
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Incidence of AKI during high-risk PCI (EF ≤35%)
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Periprocedural Creatinine Levels
1
1.2
1.4
1.6
1.8
2
2.2
0 1 2 3
Impella
ControlsP=0.04
P<0.001
Cre
ati
nin
e(m
g/d
L)
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Postprocedure Day
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
AKI Incidence ≈ Baseline CKD Severity in Unsupported Patients
Impella support *
Ejection fraction (%)
eGFR
Procedural time (min)
Contrast volume (50 ml)
AOR 95% CI p
0.09-0.31
0.12-0.28
0.25-0.83
0.71-1.13
1.28-5.14
< 0.001
<0.001
0.038
0.072
<0.001
0.13
0.16
0.63
0.98
2.14
Independent Predictors
4 620.50
Determined Whether Impella CONTINUED to Protect against AKI in
Supported vs. Unsupported HR PCI Patients (Multivariate logistic regression: controlling for clinical/procedural variables)
Despite >↓EF, >CKD,
the renal protective
effect of Impella
persisted
When controlling for contrast volume,
AKI risk was ~2 fold greater despite
Impella support
Impella CONTINUED
to be independently
associated with a
significant reduction
in AKI
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
<<AKI less likely AKI more likely>>
Summary
• The incidence of post-procedural AKI during high-
risk PCI without Impella 2.5 support is ~28% and
~5% with support; despite severely reduced EF
and baseline CKD.
The incidence of post-procedural AKI is more closely related to the
severity of baseline CKD in controls.
• Patients without Impella support presenting with severe CKD at baseline
(eGFR <30) had the highest incidence of both AKI and AKI-HD (20.5% vs. 2.7%
and 3.6% vs. <1%, respectively; p<0.05)
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
What Now?
AKI in PCI
AKI in all-comers with PCI 7-12%
Protect II: 64% non-surgical, EF-24%, CKD prevalence was 26%
and ~4% developed “acute renal dysfunction” (AKI and HD);
definition of renal failure somewhat loosely defined.
Our CKD prevalence was 50% and AKI incidence (including HD)
was ~5% ( 28% in unsupported pts)
Impella is renal protective
Tsai TT. JACC : Cardiovasc Interventions. 2014;7:1-9
Fox CS. Circulation. 2012;125:497-504
O’Neill WW, et al. Circulation. 2012;126:1717-1727
Acute Kidney Injury (AKI) is a Significant Risk
• High-risk patients face elevated
risk of AKI
Chronic Kidney Disease is a
common co-morbidity
High levels of contrast
Long procedures
• Low Ejection Fraction and baseline
hemodynamic compromise may
result in renal hypoperfusion
• Risk of AKI also exists in patients
with normal kidney function pre-
PCI
Heart Failure,
Advanced Age,
Diabetes, Chronic
Kidney Disease,
Gender, Race
Increased
Contrast
Volume
Hypotension
Risk Factors for AKI1
1. Mehran R, et al., JACC 44(7), 2004
2. Flaherty MP, et al. 2017. Circ Res;120(4):692-700
What Now?
Develop Renal Protection Risk Stratification Strategy
Our patients received ~280 cc contrast
• 2-fold incremental increase in AKI in Impella supported when
controlling for procedural and baseline characteristics
– vs. >6-fold increase in unsupported patients – contrast matters
• When feasible, patients received prehydration, high-dose statins and
non-ionic low osmolar contrast
– Did not seem to protect unsupported patients
Contrast sparing and pre-treatment are STILL less effective than Impella
Mehran: Contrast Nephropathy Risk Score
Mehran R. JACC . 2004;44:1394-99
Renal Protection Risk Stratification Strategy
• 34% - Female 22%
• 51% - DM 18%
• 62% - Previous PCI 86%
• 37% - ACS 25%
• 66% - HTN 85%
• ↑ Lesions treated 3%
• 32% - Smokers 85%
• 47% - CHF 80%
• 50% - CKD 12%
• 17% - LM disease 44%
• 91% - MVD 20%
• ↑ Procedure time (/min) 15%
• 20%, Anemia (/mg/dL) 89%
• 68% - HLD 85%
Univariate analysis14 Predictors for AKI in unsupported
AKI less likely AKI less likelyImpella Impella
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Mehran’s co-variatesage 75 years
female gender
hypertension
hyperlipidemia
diabetes
peripheral vascular disease
previous stroke
chronic kidney disease
Advanced CHF [class III/IV]
anemia
acute coronary syndrome
multivessel disease
Hypotension
IABP use
contrast media type
contrast amount 150 ml
Mehran’s Independent
Predictors for CIN (“cath AKI”)age 75 years
hypotension,
elective use of IABP
CHF (class III-IV)
CKD
anemia
diabetes
contrast volume
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
AKI Incidence ≈ Baseline CKD Severity in Unsupported Patients
Preprocedural variables (Mehran’s CIN Risk Calculator)
Using the baseline characteristics of the Impella supported
patients
• Age 66, male, white (77%)
• 51% DMII
• Hypotension (no)
• IABP (no)
• Hct > 38
• Contrast 200-300 cc
• Cr 1.49 mg/dL
CIN risk score of 14 ~26.1%, if IABP used 57%
Renal Protection Risk Stratification Strategy
Apply the Mehran CIN risk
predicting (or AKI-predicting)
scheme to each of our patients and
compare their predicted risk for AKI
with those that developed AKI.
Absolute RR
- 21%
NNT
- 5 pt
to prevent 1 AKI eventAbsolute RR
- 52%
NNT
- 2 pt
to prevent 1 AKI event
Mehran R. JACC . 2004;44:1394-99
The cVAD Study – Observed AKI in Impella Supported
HRPCI
• N=223 Patients enrolled in
prospective cVAD Study (January
2017 to March 2018)
• Elective or urgent HRPCI, supported
with Impella 2.5 (85) or Impella CP
(138) pre-PCI
• Baseline creatinine, and at least 1
follow-up creatinine within 48-72
hours of PCI, for assessment of AKI
21.4%
6.3%
8.20%
5.10%
Predicted AKI
Rate(Mehran Risk)
Score)
Observed
AKI Rate
All Impella
N=223
Impella 2.5
N=85
Impella CP
N=137
35.0%31.0%
AKI is Lower in HRPCI Patients Supported with Impella
Compared to ECMO
ECMO Impella CP
Predicted AKI Rate(Mehran Risk Score)
p= 0.55
55.0%
12.0%
Incidence of AKI
p= 0.03
ECMO Impella CP
Wiora J and Westenfeld R, et al. Presented at ACURE 2017 and Submitted to EuroInterventions. 2018
N = 28
20.0%
27.0%
AKI is Lower in Normal EF HRPCI Patients Supported with
Impella Compared to Unspupported PCI
No Support Impella
Predicted AKI Rate(Mehran Risk Score)
p= 0.1432.0%
8.0%
Incidence of AKI
p= 0.03
No Support Impella
Westenfeld R et al., ESC 2018
N = 50
Absolute RR
- 24%
NNT
- 4.2 pt
to prevent 1 AKI event
6.7%8.23%
5.79%
All
Impella
Impella
2.5
Impella
CP
cVAD Study5
32.0%
8.0%
27.8%
5.2%
Summary of AKI Data with Impella Unloading
p= 0.001
No Support Impella
2.5
55.0%
12.0%
p= 0.03
ECMO Impella
CP
Flaherty et al.1 Westenfeld et al.3,5
p= 0.001
No Support Impella
CP
Westenfeld et al.2
N=115 N=115 N=25 N=25 N=11 N=17 N=223 N=85 N=138
1. Flaherty MP, et al. Circ Res. 20:692-700 2017
2. Westenfeld R et al., ESC 2018
3. Westenfeld R et al., ACURE 2017
4. Wiora J, et al. Submitted to EuroInterventions.TCT 2018
5. Unpublished cVAD Study data, 2018
Renal Protection Risk Stratification Strategy
Our baseline Creatinine
1.26 mg/dL control
1.29 mg/dL Impella
Predictors for CIN
-age 75 years
-Hypotension,
-CHF (class III-IV)
-Anemia
-Diabetes
-Likelihood of high
contrast volume
-Consider use of
IABP
CKD III-V
Renal Protection
Risk Score 14-26% risk of AKI
Our pt had a risk score 14
and a 1 yr, Mortality risk of 14%
Reduce mortality, morbidity and costs
Cath PCI registry-based study of ~1 million pts • AKI associated with
– 10% in-hospital mortality
– AMI rates of 4%
– Major bleeding 6%
• AKI-HD associated with
– 34% in-hospital mortality
– AMI rates of 8%
– Major bleeding 16%
LOS significantly lower in Impella arm (3.5 vs 5.7 days)
We can better predict which pts will benefit from AKI risk reduction and, in the process, improve in-hospital AMI, mortality and bleeding rates and decrease LOS.
Renal Protection Risk Stratification Strategy
Tsai TT. JACC : Cardiovasc Interventions. 2014;7:1-9
Fox CS. Circulation. 2012;125:497-504
Flaherty MP, et al. 2017. Circ Res;120(4):692-700
Risk stratification
• Apply the Mehran CIN risk predicting (or AKI-predicting) scheme to each of
our patients and compare their predicted risk for AKI with those that
developed AKI.
Determine the level of protection against AKI observed with Impella.
Can we then support the use of Impella as renal protection in these patients
at high risk for AKI?
Mortality
• Is there a true AKI risk reduction associated with the use of Impella during
high contrast requiring or lengthy PCI? Does this translate into a mortality
benefit and a reduction in LOS and would this improve overall cost-
effectiveness?
Renal Protection Risk Stratification Strategy
Thank You
2626
IMPELLA® DEVICE INDICATION & SAFETY INFO.INDICATIONS FOR USE
High-Risk PCI
The Impella 2.5®, Impella CP® and Impella CP® with SmartAssist™ Systems are temporary (≤ 6 hours) ventricular support devices indicated for use during
high-risk percutaneous coronary interventions (PCI) performed in elective or urgent, hemodynamically stable patients with severe coronary artery disease, when a
heart team, including a cardiac surgeon, has determined high-risk PCI is the appropriate therapeutic option. Use of the Impella 2.5, Impella CP, and Impella CP with
SmartAssist Systems in these patients may prevent hemodynamic instability, which can result from repeat episodes of reversible myocardial ischemia that occur
during planned temporary coronary occlusions and may reduce peri- and post-procedural adverse events.
Cardiogenic Shock
The Impella 2.5®, Impella CP®, Impella CP® with SmartAssist™, Impella 5.0® and Impella LD® Catheters, in conjunction with the Automated Impella® Controller
(collectively, "Impella® System Therapy"), are temporary ventricular support devices intended for short term use (≤ 4 days for the Impella 2.5, Impella CP, and the
Impella CP with SmartAssist, and ≤ 6 days for the Impella 5.0, and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately
(< 48 hours) following acute myocardial infarction or open heart surgery or in the setting of cardiomyopathy, including peripartum cardiomyopathy, or myocarditis as a
result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures (including volume loading and use
of pressors and inotropes, with or without IABP). The intent of Impella System Therapy is to reduce ventricular work and to provide the circulatory support necessary
to allow heart recovery and early assessment of residual myocardial function.
Important Risk Information for Impella devices
CONTRAINDICATIONS
The Impella 2.5, Impella CP, Impella CP with SmartAssist, Impella 5.0 and Impella LD are contraindicated for use with patients experiencing any of the following
conditions: Mural thrombus in the left ventricle; Presence of a mechanical aortic valve or heart constrictive device; Aortic valve stenosis/calcification (equivalent to an
orifice area of 0.6 cm2 or less); Moderate to severe aortic insufficiency (echocardiographic assessment graded as ≥ +2); Severe peripheral arterial disease precluding
placement of the Impella System; Significant right heart failure*; Combined cardiorespiratory failure*; Presence of an Atrial or Ventricular Septal Defect (including
post-infarct VSD)*; Left ventricular rupture*; Cardiac tamponade*
* This condition is a contraindication for the cardiogenic shock indication only.
POTENTIAL ADVERSE EVENTS
Acute renal dysfunction, Aortic valve injury, Bleeding, Cardiogenic shock, Cerebral vascular accident/Stroke, Death, Hemolysis, Limb ischemia, Myocardial infarction,
Renal failure, Thrombocytopenia and Vascular injury
In addition to the risks above, there are other WARNINGS and PRECAUTIONS associated with Impella devices.
Visit http://www.abiomed.com/important-safety-information to learn more.
IMP-408