Temporary Devices as Bridge to More Permanent

MCSJ. Eduardo Rame

University of Pennsylvania16 May 2015

Synthesis and Overview

1. Cardiogenic Shock and Consideration for EARLY Extracorporeal Support

2. Case Presentation: Recovery on HMII LVAD after Resussitation with Percutaneous LVAD, ECMO in postpartum shock

3. TCS as a Bridge to Durable Mechanical Suppot: Data from the Interagency Registry for Mechanical Circulatory Support (INTERMACS)

The transition to durable mechanical circulatory support is The transition to durable mechanical circulatory support is difficult, with challenges post-cardiotomy to right ventricular difficult, with challenges post-cardiotomy to right ventricular adaptation to left sided support. The presence of cardiogenic adaptation to left sided support. The presence of cardiogenic shock is known to present additional and sometimes shock is known to present additional and sometimes prohibitive risk. The use of Temporary Circulatory Support prohibitive risk. The use of Temporary Circulatory Support (TCS) devices can mitigate the risk of this transition. (TCS) devices can mitigate the risk of this transition.

Cardiogenic Shock: A Spectrum of Perfusion

• Spectrum: Low cardiac output state with organ hypoperfusion, but with systolic blood pressure >90 mmHg in response to inotropes without the use of an IABP

• Spectrum: Profound hypoperfusion with cardiac index <1.8 l/min/m2 with mean blood pressure <65 mmHg and unresponsive to inotropes—catecholamine refractory.

End-Organ Dysfunction: Pathogenesis

• Cellular and tissue-level hypoxia– Trans-organ gradient (MAP – CVP) of perfusion– Factor of an elevated CVP – congested organs

are not well perfused even with MAPs> 60 mm – Metabolic Shift to Glucose under hypoxic

conditions is adaptive but once liver failure with failed gluconeogenesis - Energetic Failure

– Remember the RV: needs preload, reduced afterload, but a good MAP to maintain function

– Failing RV Glucose dependent and PERFUSION Dependent

Systemic Systemic Venous Venous CongestionCongestion

Systemic Systemic Venous Venous CongestionCongestion

Neurohumoral and Systemic Inflammatory

Activation

Neurohumoral and Systemic Inflammatory

Activation

Multi-System (Brain, Renal, Liver…) Organs Failing

Multi-System (Brain, Renal, Liver…) Organs Failing

Right Right Ventricular Ventricular Dysfunction Dysfunction

Right Right Ventricular Ventricular Dysfunction Dysfunction

Prognostication and Risk: Non-Invasive Model

(N=1217, SHOCK Trial and Registry)57% 30 day Mortality

Variable Estimate SE Odds ratio P value

Age 0.047 .006 1.27 per 5-y increase <.001

Anoxic brain damage 3.069 .799 21.52 .0001

End-organ hypoperfusion 1.425 .333 4.16 <.001

Shock on admission 0.654 .179 1.92 .0003

Prior CABG 0.694 .235 2.00 .0032

Noninferior MI⁎ 0.327 .137 1.39 .0172Sleeper, et al. AHJ 2010

Prognostication and Risk: Invasive Model with PAC

(N=857, SHOCK Trial and Registry)57% 30 day Mortality

Variable Estimate SE Odds ratio P value

Stroke work, g/m†,‡ −.0358 .0069 0.84 per 5 units <.001

LVEF <28%† 0.7880 .1924 2.20 <.001

Age, y .0413 .0072 1.23 per 5 yr <.001

Anoxic brain damage 2.4902 .8168 12.1 .002

End-organ hypoperfusion 1.3667 .3889 3.92 <.001

Sleeper, et al. AHJ 2010

Percutaneous Mechanical Support Options

Temporary Circulatory Support (TCS) includes IABP, Impella Family, Tandem Heart, and ECMO

CASE Presentation: Peripartum Cardiomyopathy in Cardiogenic

Shock

• 19 y/o Female Presented 3 weeks after a well-tolerated C-Section with fulminant cardiogenic shock (12/5/2012)– Asysolic Arrest – Severe Cardiomyopathy– Depressed mentation– Metabolic Acidosis

• Failed Impella with Hypotension and ongoing multi-organ system failure (30 Levophed, 10 Epi, 300 Neo, 0,08 Vasopressin, Milrinone)– ATN (Gross Hemolysis in Urine)– Acute Liver Injury with Necrosis– Pulmonary Edema

ECMO : 12/6• 12/06/2012 Placed on VA ECMO in the OR with 5.5 L/min flow• A HeartPort Swan suction catheter was advanced into the PA

which provided an additional 600 mL of flow and drainage leading to a total flow of 6.2 liters at 4700 rpm.

CVP was approximately 18-20The patient began to diurese in OR and the acidosis began to be corrected with ECMO in the OR.

• All drips were removed except for milrinone and 2 of epinephrine

• Over the next week -- She improved from all end-organ perspectives except renal ( Serum creatinine rose to 7 requiring CRRT) – Neurologically intact– Pulmonary edema resolved but could not be extubated -- ?

Pneumonia/pneumonitis– Echocardiogram : LVEF < 10% with evidence of Non-Compaction– WBC persistently in the 50,000 – no fevers but persistently tachycardic

12/13/2012: HM II Implant

• There was heavy trabeculation of the apex and this was excised aggressively.

• Pataient was easily weaned from cardiopulmonary bypass to LVAD support and RV function was normal. Flows were approximately 4.2 liters on 8600 rpm with the CVP in the single digits.

• Clinical Improvement Post-implant was marked– Renal Function Recovered (2 week CRRT)– She did require Tracheostomy for a slower vent wean

(deconditioned/recovery from Pneumonia)– LVEF Improved [ Results of Myocardial Core – mild

Lymphocytic Carditis without Necrosis/Fibrosis consistent with Peripartum CM]

Outcomes after Ventricular Assist Device Support in Patients Bridged with Temporary Circulatory Support: Analysis from INTERMACS

S Shreenivas1, K Hudock2, S Myers3 A Acker4, P Atluri4, M Acker4, El-Banayosy

A5, FD Pagani6, P Bonde7, Francisco Arabia, JK Kirklin5, JE Rame1

Hypothesis: The Use of TCS as a bridge to permanent MCS can allow patients with end-organ dysfunction due to cardiogenic shock to have satisfactory outcomes after VAD therapy.

Comparison of Baseline Characteristics

Demographics No TCS TCS P-value

Age (yrs) 55.81 55.06 0.12

Male 77.6% 82.2% 0.30

White 66.2% 70.8% < 0.0001

BSA (m2) 2.07 2.06 0.27

Tobacco use 9.5% 17% < 0.0001

Diabetes 39.3% 36.5% 0.11

CAD 6.3% 12.3% <0.0001

CVA 8.1% 7.8% 0.76

PVD 6% 5.1% 0.28

Inotropes 93% 89.4% 0.0002

Comparison of Baseline Hemodynamics Pre-LVAD ImplantHemodynamics No TCS TCS P-valueHeartrate (bpm) 89.26 91.14 0.0027

Systolic BP (mmHg)

103.65 100.83 <0.0001

Diastolic BP (mmHg)

64.47 61.62 <0.0001

LVEF (< 20%) 71.8% 73.2% 0.40RVEF (severe) 21.4% 23.9% 0.22

LVEDD 6.91 6.79 0.02Mod/Severe MR 61.4% 59% 0.19Mod/Severe TR 48.3% 45.6% 0.15Cardiac Index 2.08 2.18 0.0023

Wedge Pressure 23.78 24.85 0.02PVR (wood units) 2.83 2.65 0.14

Comparison of Pre-Implant End-Organ Indices

Co-morbidities No TCS TCS P-value

Ventilator 2.2% 15% <0.0001

Hemodialysis 0.9% 3.2% <0.0001

BUN 29.68 31.57 0.01

Cr 1.42 1.49 0.01

Ascites 6.6% 8.8% 0.03

Total Bilirubin 1.26 1.70 <0.0001

AST 48.60 103.08 <0.0001

ALT 57.08 109.21 <0.0001

Adult Primary Continuous Flow LVADs for Patient Profile Levels 1,2,3, n=3354

% Survival Stratified By TCS

Months post implant

Event: Death (censored at transplant and recovery)

% S

urvi

val

Grp 2 & 3: TCS, n=1363Deaths=291

INTERMACS: March 2009 – March 2012: temporary support

Grp 1: No TCS, n= 1991Deaths=348

p (unadjusted) = .002p (adjusted for risk factors) = 0.16

Figure 3

% Survival Mths Grp1 (n) Grp2 (n) 1 96% (1845) 94% (1238) 3 92% (1571) 88% (1023) 6 88% (1200) 84% (786) 12 82% (695) 77% (439) 24 72% (176) 67% (115) 36 59% (7) 51% (6)

Timing of TCS Relative to LVAD Implantation

Which Therapy?

Or Is it Time for ECMO ?

Platform of TCS and Post-LVAD Survival

Adult Primary Continuous Flow Bi-VADs for Patient Profile Levels 1,2,3, n=111

% Survival Stratified By TCS

Months post implant

Event: Death (censored at transplant and recovery)

% S

urvi

val

Grp 2 & 3: TCS, n=73Deaths=26

INTERMACS: March 2009 – March 2012: temporary support

Grp 1: No TCS, n= 38Deaths=19

p (unadjusted) = .18P (adjusted) = 0.06

% Survival Mths No TCS (n) TCS (n) 1 68% (27) 94% (57) 3 60% (23) 88% (47) 6 51% (18) 84% (41) 12 45% (12) 77% (33) 24 51% (7) 67% (10) 36 51% (1) 51% (1)

Adult Primary Total Artificial Hearts (TAH)for Patient Profile Levels 1,2,3, n=71

% Survival Stratified By TCS

Months post implant

Event: Death (censored at transplant and recovery)

% S

urvi

val

Grp 2 & 3: TCS, n = 42

INTERMACS: March 2009 – March 2012: temporary support

Grp 1: No TCS, n=29

p (unadjusted) = .57

% Survival Mths No TCS (n) TCS (n) 1 94% (29) 84% (32) 3 94% (20) 84% (19) 6 77% (8) 84% (8) 12 77% (5) 84% (2) 24 77% (1) --- (1) 36 77% (1) --- (1)

Summary and Future Direction

• Cardiogenic Shock in patients with and without advanced heart failure carries a poor prognosis

• TCS strategies are deployed to abrogate the cascade of hypoperfusion , inflammation, and cell/tissue/organ death that is present

• Long Term MCS platforms such as LVADs, BiVADs, and TAHs can deliver acceptable survival in patients who are bridged with TCS devices

• Research in identifying mechanisms of injury and protective strategies to improve end-organ function after resussitation is long overdue

• Future work describing if reasonable end-organ functional indexes (neurocognitive, renal) and functional capacity can be achieved with TCS as a bridge to long term MCS would be of interest

Acknowledgements

• Satya Shreenivas• David Naftel• Susan Myers• Frank Pagani• Jim Kirklin• Francisco Arabia• Aly El-Banayosi• Alexandra Acker• Michael Acker• Pavan Atluri

• Pascal LePrince

Percutaneous LVADImpella 2.5, CP, 5.0

Tandem Heart15 - 17 F arterial sheath, 22 F venous sheath

Transseptal Puncture

Response to IABC: Reversal of Hypoperfusion

Ramanathan, AHJ 2011

Baseline Hemodynamics in CRH

Hemodynamic Response in CRH

30 day* and 1 Year Survival Improved if CRH Achieved

Multivariate Adjustment: CRH persists as a predictor of survival

VA ECMO RISK(CO Support and Central Venous Decongestion)

A. Systemic Inflammatory SyndromeB. Acute Kidney Injury (with or without A)C. Pulmonary Edema and Lung Injury (ECMO LUNG) –

less likely with antegrade flow from central surgical cannulation

D. Lack of Mechanical Unloading of the LV (increased Preload and Afterload)

E. Lower Limb IschemiaF. CVA – ischemic and hemorrhagicG. Blood Trauma – May limit time to RecoveryH. Bleeding