update on treatment options for end stage...
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UPDATE ON TREATMENT OPTIONS FOR END STAGE HEART FAILURE
Jerry D. Estep, MD, FACC, FASE
Associate Professor of Clinical Cardiology Houston Methodist Institute of Academic Medicine Section Head of Heart Transplant and Mechanical Circulatory Support, Division of Heart Failure Medical Director, Heart Transplant & LVAD Program
DISCUSSION AIMS
• Provide an update on the following:– Heart transplant volume, survival, and donor and
recipient characteristics – Highlight risk factors for post transplant mortality– Current LVAD outcome and future technology
• Provide an outcome update/end stage HF initiatives at Houston Methodist
ADULT AND PEDIATRIC HEART TRANSPLANTSNUMBER OF TRANSPLANTS BY YEAR AND LOCATION
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
Num
ber o
f tra
nspl
ants
Other
Europe
North America
2015JHLT. 2015 Oct; 34(10): 1244-1254
2015 NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, the presented data may not mirror the changes in the number of heart transplants performed worldwide.
ADULT AND PEDIATRIC HEART TRANSPLANTSAVERAGE CENTER VOLUME(TRANSPLANTS: JANUARY 2009 – JUNE 2014)
4455
116
41
13 5 7 30
10
20
30
40
50
60
0
20
40
60
80
100
120
1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+
% o
f tra
nspl
ants
Num
ber o
f cen
ters
Average number of heart transplants per year
Number of centers Percentage of transplants
2015JHLT. 2015 Oct; 34(10): 1244-1254
2015
(284 centers)
ADULT AND PEDIATRIC HEART TRANSPLANTSRECIPIENT AGE BY YEAR OF TRANSPLANT
0
10
20
30
40
50
60
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Med
ian
reci
pien
t age
(yea
rs)
% o
f tra
nspl
ants
0-9 10-17 18-39 40-59 60-69 70+ Median Age
2015JHLT. 2015 Oct; 34(10): 1244-1254
2015
ADULT AND PEDIATRIC HEART TRANSPLANTSMEDIAN RECIPIENT AGE BY LOCATION
40
45
50
55
60
Med
ian
reci
pien
t age
(yea
rs)
Europe North America Other
0
10
20
30
40
50
60
70
0-9 10-17 18-39 40-59 60-69 70+
% o
f tra
nspl
ants
Recipient Age
1982-1998 (N=57,137)
1999-2008 (N=39,879)
2009-6/2014 (N=22,781)
p < 0.0001
ADULT AND PEDIATRIC HEART TRANSPLANTSRECIPIENT AGE DISTRIBUTION BY ERA
ADULT AND PEDIATRIC HEART TRANSPLANTSMEDIAN DONOR AGE BY LOCATION
20
25
30
35
40
45
50
Med
ian
dono
r age
(yea
rs)
Europe North America Other
ADULT AND PEDIATRIC HEART TRANSPLANTSDONOR AGE DISTRIBUTION BY LOCATION (TRANSPLANTS: JANUARY 2009 – JUNE 2014)
0%
20%
40%
60%
80%
100%
Europe North America Other
% o
f don
ors
0-9 10-17 18-39 40-59 60-69 70+
ADULT AND PEDIATRIC HEART TRANSPLANTSKAPLAN-MEIER SURVIVAL BY AGE GROUP (TRANSPLANTS: JANUARY 1982 – JUNE 2013)
0
25
50
75
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Surv
ival
(%)
Years
Adult (N=100,806)
Pediatric (N=11,384)
Median survival (years): Adult=10.3; Conditional=13.0Pediatric=15.3; Conditional=20.0
STABLE HEART TRANSPLANT RECIPIENT SURVIVAL OVERTIME
Lund L. et al. ISHLT 31st Report-2014 JHLT 2014
CATEGORICAL RISK FACTORS FOR 1 YEAR MORTALITY AFTER HEART TRANSPLANT
Multivariate analysis ISHLT Registry(10, 739 Heart Transplant Recipients 2007-2012)
Lund L. et al. 31st Report JHLT 2014
LVAD BTT IS NOT A BENIGN STRATEGY FOR SOME PATIENTS
ISHLT 2016 Submission
Methods: All adult BTT pts that received a heart transplant from 2008 to 2014 were identified using the United Network for Organ Sharing (UNOS) database. 2008-2012 transplants were used to derive our risk score and 2013 – 2014 to validate it. Univariate and multivariate Cox proportional-hazards models were performed. Risk factors were assigned weightage using linear transformation and risk score was derived. Pts were consolidated into three categories: low-risk, medium-risk and high-risk group.
The derivation cohort had 2,384 pts and the validation had 1,758
HISTORY OF TRANSPLANT AND MECHANICAL SUPPORT AT HOUSTON METHODIST
•1968: One of world’s first heart transplants
•1968: First multi-organ donor—one donor saved the lives of four people
•1985: Texas’ first heart/lung transplant
•2000: Nation’s first implantation of the MicroMed DeBakey-Noon ventricular assist device
•2005: World’s first multi-organ transplant in patient with ventricular assist device
•2006: World’s first patient to undergo chemotherapy while implanted with ventricular assist device
•2009: Performed Heart/Double Lung/Liver transplant- one of only 10 reported cases in the nation
ADVANCED HF EVALUATIONS
Referred Patients (~ 350 patients)
Assessment Made1. End stage heart disease 2. Institutional criteria for LVAD and/or Heart Transplant3. Benefit versus risk assessment
Strategy Decision Recommendation
1. Direct to heart transplant2. BTT LVAD3. DT LVAD
HOUSTON METHODIST TRANSPLANT VOLUME (TOP 10% BASED ON ISHLT 284 CENTER DATA)
36
0
5
10
15
20
25
30
35
40
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015QTR 1-3
Heart Heart-Lung
Privileged and Confidential PI Document
2015 Project Total: 38
HEART: Total UNOS Median Days to Transplant
Privileged and Confidential PI Document
95
72
50
81
5147
0
10
20
30
40
50
60
70
80
90
100
2010 2011 2012 2013 2014 2015QTR 1-3
PRE OUTCOMES
HEART: Medical Urgency for Transplant: Status
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
2012 2013 2014 2015QTR 1-3
SRTRRegion
SRTRNation
1A1B2
TRANSPLANT OUTCOME
Privileged and Confidential PI Document
SRTR Data 2015
*SRTR Release June 2015 (1/1/14 – 12/31/14)
EXTENDED LEFT AXILLARY IABP SUPPORT PERMITS DIRECT BTT
Step 1 - J-guide wire (using fluoroscopy) inserted into the left axillary/subclavian
Access ( N= 101, 50 in publication plus 55)Step 1 - J-guide wire (using fluoroscopy) inserted into the left axillary/subclavian artery to serve as roadmapStep 2 - Direct axillary artery puncture using a micro puncture (VaxcelTM Mini StickTM kit) or standard percutaneous needle Step 3- Place 4F sheath/upgrade to 7.5 Linear IABP
HOUSTON METHODIST OUTCOME
Fall 15 (7/1/12-12/31/14) Spring 16 (1/1/13-6/30/15)HMH Observed 88.89% 91.07%HMH Expected 89.99% 89.57%National 90.64% 90.64%
60%
65%
70%
75%
80%
85%
90%
95%
HMHObservedHMHExpected
PROJECTED
HEART: SRTR 1 Year Patient Survival
HEART TRANSPLANT PROGRAM3 YEAR Patient Survival
34%
22%
19%
12%
7%6%
RCA Contributing Factors
Process
Patient Selection
Immediate PerioperativeCare
TX Procedure
Patient Status at TX
Donor Selection
Process Related Factors: • Policy & Procedure• Communication among • Team members• Equipment
maintenance/ management
• Staffing
15 Total Cases (2010 – 2013)13 Deaths3 Graft Failures (1 death w/ concomitant GF)N = 466 Identified Factors
MINIMALLY INVASIVE HEART TRANSPLANT PROTOCOL
HEART TRANSPLANTATION IN PATIENTS WITH INFILTRATIVE CM
A MULTI-CENTER, INTERNATIONAL REGISTRY OF CARDIAC TRANSPLANTATION AMYLOIDOSIS
Marc Semigran MD, Jerry D. Estep MD Lauren Gilstrap MD, Emily Niehaus BA, Mathew Maurer MD, Ron Witteles MD, Giuseppe Feltrin MD, Mark Zucker MD, David Baran MD, David Seldin MD
Database: Total of 177 patients. 123 patients AL and
44 are listed as TTR subtype
Massachusetts General Hospital, Boston, MAHouston Methodist Hospital, Houston, TXStanford University Medical Center, Stanford, CAUniversity of Padova, Padova, ItalyNewark Beth Israel Medical Center, Newark, NJBoston University Medical Center, Boston, MACedars Sinai Hospital, Los Angeles, CACleveland Clinic, Cleveland, OHUniversity of California San Francisco, San Francisco, CAColumbia Medical Center, New York City, NY
SURVIVAL OF AMYLOID PATIENTS AFTER HEART TRANSPLANTATION
iCCAT ACC Scientific Sessions 2014 and 2015
Heart-Liver
-97 cases of OHT and Liver txp-96,033 liver alone txp-67,852 heart alone txp
U.S. Donor Heart Supply Is Limited
Heart Transplantation remains the most effective treatment for end-stage heart disease, although donor shortage limits its use 1-year survival: ~ 90% Houston Methodist ~ 89% 5-year survival: ~75% Houston Methodist ~ 75% 10-year survival: ~55%
UNOS Website: http://optn.transplant.hrsa.gov and 2015 SRTR Report
PATIENTS MAY NOT QUALIFY FOR CARDIAC TRANSPLANT
General Specific Relative Any condition limiting a
successful transplant outcome
Elevated pulmonary vascular resistance
Active infection
Shock with MOF
Advanced renal or pulmonary disease
Cross-match incompatibility
Active psychiatric disease
Substance abuse/smoking
Age
Peripheral vascular disease
Malignancy
Size/Obesity
Diabetes with end organ damage
LVAD is an option Destination Therapy = Extended Support for Life
Option for patients who may not qualify for cardiac transplantation
INCREASED UTILIZATIONS OF LVADS
Kirklin et al. 6th INTERMACS Annual Report. JHLT 2014;33:555-564
DESTINATION VAD THERAPY AND IMPROVED PATIENT ONE YEAR SURVIVAL ~ 75-80%
Jerry D. Estep, MD JACC Vol. 66. NO 16. 2015
CONTEMPORARY DT LVAD IMPLANTATION CRITERIA
Destination Therapy• LVEF ≤ 25%• Peak VO2 < 14 ml/kg/min (or 50% age/sex
predicted)• And either
• NYHA Class IIIb-IV symptoms despite optimal medical therapy for at least 45 of the prior 60 days, or
• Dependence on IV inotropes for ≥14 days, or• Dependence on IABP for ≥ 7 days
• Not a transplant candidate
ENDURANCE STUDY-HVAD DT
FD Pagani ISHLT 2015
Prospective and randomized trial to compare safety and effectiveness of the HVAD systemto a FDA approved LVAD in End StageHF patients not transplant eligible
ENDURANCE STUDY-HVAD DT
FD Pagani ISHLT 2015
ENDURANCE PATIENT POPULATION
FD Pagani ISHLT 2015
ENDURANCE STUDY:SIMILAR FUNCTIONAL CAPACITY IMPROVEMENT
FD Pagani ISHLT 2015
ENDURANCE STUDY:SIMILAR QUALITY OF LIFE IMPROVEMENT
FD Pagani ISHLT 2015
ENDURANCE :ADVERSE EVENTS
ENDURANCE:BP MANAGEMENT IS KEY
NEW DEVICE/NEW HORIZONS
• Pump rotor is levitated and completely suspended by magnetic forces
• Rotor stays centered in pump housing regardless of its orientation
• Full levitation even at zero speed
CAUTION – Investigational device. Limited by US Federal law to investigationalClinicalTrials.gov Identifier: NCT02224755
US-HM3-04150222
Minimize interactions between the blood and the contacting surfaces
Minimize flow patterns that reduce activation of
blood components
Minimize stasis
Minimize shear stress
HM III EUROPEAN EXPERIENCE
MOMENTUM III CLINICAL STUDY: MOVING AWAY FOR BTT/DT LABELING
CAUTION – Investigational device. Limited by US Federal law to investigationalClinicalTrials.gov Identifier: NCT02224755
US-HM3-04150222
HeartMate III is designed for a broad range of advanced heart failure patients to restore blood flow while improving survival, functional status and quality of life.• Additional details about the
study can be obtained by visiting http://clinicaltrials.gov
• ClinicalTrials.gov Identifier: NCT02224755
Potential Candidate
NYHA Class III with dyspnea
upon mild physical
activity, or NYHA
functional class IV
Adults with BSA >1.2 m2
Inotrope dependent
ORCI <2.2 while
not on Inotropes
LVEF <25%
HEART PROGRAM VOLUME(END ORGAN INTERVENTIONS)
33
45
6457
71 68
91
78 8293
0102030405060708090
100
* Includes heart transplant, multi-organ transplant including a heart allograft , and VAD implants
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
ADVANCED INTERVENTIONS FOR HEART FAILURE
Investigators:
Jenny Blumenthal-Barby, PhD Courtenay Bruce, JD, MA Robert Volk, PhD Jerry Estep, MD Sheryl McCurdy, PhD Charles Minard, PhD
Significant Contributors:
Matthias Loebe, MD, PhDBrian Bruckner, MD
Patient Partners:
• Brenda Mays• Kenneth Mitchell• Mary Yorgensen,
RN
Research Staff:
• Kristin Kostick, PhD
• Estevan Delgado
Specific Aim 1: Develop a patient-centered decision aid for decision-making about advanced heart failure treatment (Completed)Specific Aim 2: Validate –Multicenter Initiative –Houston Methodist, Texas Heart, Cleveland Clinic, Oschner Clinic, Baptist Integris, and Aurora Health.
Lvaddecisionaid.com
ROADMAP AND MEDAMACSPATIENT PERCEPTIONS
1. Estep, JD et al. ROADMAP trial. JACC 2015 2. Garrick, Stewart et al. MEDAMACS. JHLT in press. 09/2015 (online)
ROADMAP
MEDAMACS
Lvaddecisionaid.com
LVADDECISIONAID.COM
Lvaddecisionaid.com
INTERMACS 4+ Profile
-INTERMACS 4+
• Bleeding (GI bleeding) is the most common adverseevent
• Hospital readmissions arecommon for patients thatelect optimal medical management and for those after LVAD placement
• Watchful waiting on OMMis associated with disease progression and increasedseverity of illness for many patients
LVAD DECISION AID
VAD: DESTINATION THERAPY POST OUTCOMES
INTERMACS 2015 Q1 (June 2015) Report: Data June 23, 2006 - March 31,2015
INTERMACS Right heart failure (Episodes per 100 pt months)
VAD PROGRAM
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
HMH INTERMACS
Early (<3 months)Late (>3 months)
INTERMACS 2015 Q1 (June 2015) Report: Data June 23, 2006 - March 31,2015
ECHOCARDIOGRAPHY IS KEY IN THE SELECTION AND MANAGEMENT OF LVAD PATIENTS
PROTOCOLS ARE KEY TO MANAGE LVAD PATIENTS
Are you experiencing shortness of breath and/or leg swelling? (Left and/or right sided heart failure)
Have you noticed the development of dark urine? (Acquired hemolysis and rotor pump thrombosis)
Are you experiencing fatigue? (Heart failure and/or hemolytic anemia and/or acute blood loss anemia and GI bleeding)
Have you experienced darker and/or bloody stools? (GI bleeding secondary to acquired AVMs)
Have you noticed drainage and/or pain around your (LVAD related infection)driveline exit site?
Have you experienced fever and/or chills? (LVAD related infection)
Have you experienced any alarms? If so, what kind? (See Table 4 and 5 for Differential)
Have you had any incidence of trauma to driveline? (Driveline fracture)
Questions Possible Diagnosis
LVAD specific Review of Symptoms and Possible Underlying Diagnosis
TEMPLATES AND PROTOCOLS TO MANAGE LVAD PATIENTS ARE HELPFUL
IMPROVEMENT IN FUNCTIONAL CAPACITY
GOAL IS TO ALSO IMPROVE QUALITY OF LIFE
LONG-TERM OUTCOME DATA IS NEEDED
END STAGE HF TREATMENT OPTION SUMMARY
• Heart transplantation remains the most effect intervention associated based on decades of experience and long-term outcome data.
• A limited donor supply and patient relative/absolute contraindications limit its use.
• Long-term survival and quality-of-life metrics are encouraging with current LVADS (1 year survival ~ 75 to 80%).
• Adverse event (AE) burden with LVADs remains challenging.• Ongoing MOMENTUM HM III Trial will be the next landmark trial that
examines current safety and efficacy • At the local level a multi-disciplinary team with inclusion/exclusion
criteria, protocols and best practice polices and consistent high quality performance initiatives is necessary to offer and achieve the best life saving intervention results
FROM OUR TEAM TO YOURSTHANK YOU !
• Raquel R. Bunge, RN, BSN, CCRC, HF Clinical Trials Manager
• Trang T. Doan, MBA, Operations Manager III• Manuel Rojas, Financial Analyst • Deborah Barr RN, BSN Clinical Research Nurse• Michelle Prystash, RN Clinical Research Nurse• Patricia Moore, RN, MBA Clinical Research Nurse • Colleen Brown, RN, Clinical Research Nurse• Martha L. Jones, CCRP, Regulatory Compliance Specialist
CLINICAL Trial Research Team
LVAD AND TRANSPLANT COORDINATORS
PERFUSION TEAM
HEART FAILURE NURSE PRACTIONERS/PALOREN SEMONES, DANELLE MCLAIN, BRITTANY COLE
QUALITY PERFORMANCECOORDINATORS
Guillermo Torre
MD, PhD
Jerry EstepMD
Arvind BhimarajMD
Barry Trachtenberg
MD
Guha AshrithMD
Myung ParkMD
HF CARDIOLOGY
Scott Scheinin, MD
Brian Bruckner
MD
Erik Suarez
MD
SURGERY
George P NoonMD