OUTCOMES OF LUNG

TRANSPLANTATION IN PAH

VIJIL RAHULAN, MD, FCCP (USA), AB (PULMONARY/CCM)

CHIEF, TRANSPLANT PULMONOLOGY
KIMS HEART & LUNG TRANSPLANT INSTITUTE, HYDERABAD
Outline

 Challenges of Organ Transplantation for PAH

 Lung Transplant vs Heart-Lung Transplant
 Deploying ECMO in the setting of PAH
 Outcome data on transplantation in PAH
Place of Lung Transplantation in PAH Management
RV STRAIN Increased Risk of Sudden
PREDICTS Cardiac Death in PAH
OUTCOMES IN •
•
Arrhythmias
Non arrhythmic causes
PAH - Left Main Compression sm
-Pulm Art Dissection & Rupture
-Hemoptysis
-Syncopy
-cardiac arrest
REVEAL Registry
Updated PAH Risk Score
2015 ESC/ERS Guidelines
Risk Assessment in PAH
Lung Transplantation in PAH

 Lung transplant is a viable option in PAH to improve life expectancy and quality
of life
 Double lung transplant is preferred
• Improved outcomes when compared to single lung transplant recipients
• Risk of recurrence of PAH after single lung transplant
 Some patients require heart-lung transplantation when they have severe RV
failure or anatomical abnormalities
Lung Transplantation in PAH: Numbers

 January 2004-June 2015 ISHLT Registry had 32,237 lung transplant recipients
• 897 of them were IPAH and 276 PH-not IPAH (3.6% of lung transplants)
 January 2004-June 2015 ISHLT Registry had 812 combined heart-lung
transplant recipients
• 222 IPAH (27.3% of combined heart-lung transplant recipients)
 Thus, 4.1% of all lung or heart-lung transplant recipients have pulmonary
hypertension as primary diagnosis

2016
 Challenges of Organ Transplantation in PAH: Allocation

Lung Transplants Over Time Heart-Lung Transplants Over Time

4500 300

4000
250
Bilateral
3500
Single Lung
3000 200

2500 15
2000 0

1500 10
0
1000 50
500
0
0

2016
2015 LAS Revision

 Revision to LAS was made on February 19, 2015

• Now used Cardiac Index and CVP in algorithm
‒Previous collected but not used
• Total Bilirubin was added to algorithm
• Adjusted 6MWD cut offs for impact on score
 Adult Lung Transplants
Kaplan-Meier Survival by Major Diagnosis
(Transplants: January 1992 – June 2017)
100 A1ATD (N=3,257) CF (N=9,428)
COPD (N=19,159) IIP (N=15,574)

75 Median survival (years):

A1ATD: 7.1; CF: 9.9; COPD: 6.0;
Survival (%)

IIP: 5.2; ILD-not IIP: 6.7; IPAH: 7.0

50

25
All pairwise comparisons were significant
at p < 0.05 except A1ATD vs. ILD-non IIP,
A1ATD vs. IPAH, COPD vs. ILD-non IIP, and
ILD-non IIP vs. IPAH.

0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Years
2019 1, 3, 5, 10 YR SURVIVAL RATES
JHLT. 2019 Oct; 38(10): 1015-1066 74.3%, 64.2%, 56.1%, 41.4%
Type of Organ Transplant: Single vs Double
 Conte JV et al. Ann Thorac Surg. 2001
 15 PAH lung transplant recipients at Johns Hopkins
Type of Organ Transplant: Single vs Double

 Consensus became that double lung transplantation was preferred to single

• Risk of recurrence of PAH
• Better long term outcomes
Type of Organ Transplant: SLT vs DLT vs HLT

 Toyoda et al. Ann Thorac Surg. 2008

 59 PAH patients undergoing transplant at Pittsburgh
Contemporary
Double

Single
HLT Historical
Type of Organ Transplant: Lung vs Heart-Lung

 De Perrot et al. J Thorac Cardiovasc Surg. 2012

 79 patients with Pulmonary Hypertension in Toronto
Type of Organ Transplant: Lung vs Heart-Lung

 Historical Studies demonstrated survival benefit of double lung transplant over

combined heart-lung transplant
 Not seen in more contemporary studies
 Kaplan-Meier Survival for IPAH by Organ Type -January 1990-June 2014
Heart-Lung Lung Transplant
100

75
Survival (%)

50

25

0 0 1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 20

11

Years
2016
USE OF ECMO IN TRANSPLANTATION
IN PAH

• BRIDGING
• INTRA OP
• POST OP
ECMO CONFIGURATIONS
BRIDGING STRATEGY
ProtekDuo ECMO
Entered back into
body via pulmonary
artery

Passes
through
oxygenator

Venous
blood comes
out of Right
Atrium
Extracorporeal Membrane Oxygenation: ProtekDuo

 Pro:
• Can mobilize in patients with RV failure
• More physiologic circulation
• Acts as RV Assist Device
 Con:
• High rates of hemolysis
• Can flip into RV if cannula is too short
• Very complex placement
Other Bridging Techniques

 Novalung – pumpless ECMO, not approved by FDA

 Atrial Septostomy
• Creation of inter-atrial right-to-left shunt
 Transcatheter Potts Shunt
• Connect the left pulmonary artery to the descending aorta

Corris & Degano Eur Respir Rev. 2014

Ann Cardiothorac Surg 2020;9(1):29-41 |
PERIOPERATIVE ISSUES OF PAH PTS
UNDERGOING TRANSPLANTATION

• PGD - Reperfusion Injury

• ↓PVR & Hyperdynamic RV →Pulmonary hyperperfusion
• PostOp LV Dysfn ( preload & Afterload related )

100
Survival (%)

75
50
25
0 Years
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
EXPERIENCE DATA FROM HIGH VOLUME
CENTERS
 POST OP DATA

RECEPIENT DATA
 The Journal of Thoracic and Cardiovascular Surgery . March 2018

Results: Between January 2006 and September 2016, 1111 LTx were performed in our institution. ECLS was used in 71 adults with
the intention to bridge to LTx; of these, 11 (16%) were bridged to retransplantation.
The median duration of ECLS before LTx was 10 days (range, 0-95). We used a single dual-lumen venous cannula in 23 patients
(32%). Nine of 13 patients (69%) with pulmonary hypertension were bridged by central pulmonary artery to left atrium Novalung.

Twenty-five patients (35%) were extubated while on ECLS and 26 patients (37%) were mobilized. Sixty-three patients (89%)
survived to LTx. Survival by intention to treat was 66% (1 year), 58% (3 years) and 48% (5 years).
Survival was significantly shorter in patients undergoing ECLS bridge to retransplantation compared with first LTx (median survival,
15 months (95% CI, 0-31) versus 60 months (95% CI, 37-83); P ¼ .041).

Conclusions: In our center experience, ECLS bridge to first lung transplant leads to good short-term and long-term outcomes in
carefully selected patients. In contrast, our data suggest that ECLS as a bridge to retransplantation should be used with caution. (J
Thorac Cardiovasc Surg 2018;155:1316-28)
BRIDGING DEVICES
AMBULATION
 OUR EXPERIENCE..

Summary of Demographic and anthropometric parameters (N=132)

Demographic and anthropometric parameters Summary

Presenting Diagnosis N = 132
ILD 87 (65.91%)
Bronchiectasis 13 (9.85%)
Primary pulmonary hypertension (PPH) 9 (6.82%)
Congenital Heart Disease (CHD) 6 (4.55%)
COPD 7 (5.30%)
Cystic fibrosis 3 (2.27%)
Others 7 (5.30%)

Transplant type
Bilateral LUNG Transplant 102 (77.3%)
Bilateral LUNG Transplant, CABG 4 (3%)
HEART AND LUNG Transplant 19 (14.39%)
SINGLE LUNG Transplant 7 (5.30%)
Figure 1: Kaplan-Meier survival analysis depicting cumulative survival

N = 132
PAH (N=9) N (%)
Age (Mean) 33.21
Gender N (%)  
Male 2 (22%)
Female 7 (88%)

Summary of the type of transplantation and intra-operative and post-operative findings. (N= 9)
Surgical data Summary
Transplant type
Bilateral Lung transplant 1
Heart & Lung Transplant 8
Single Lung Transplant 0
Intra-operative ECMO 1
Intra-operative CPB (ON pump) 8
Intra-operative CPB Time (hours) N = 8 4.24
Intra-operative ECMO Time (hours) (N=1) 3.40
Ischemia Time (hours ((N=9) 4.21
Post-operative ECMO 2
Tracheostomy 1
Days on Ventilator (Mean) 4.67
Days in ICU (Mean) 16.69
Days in Hospital (Mean) 24.31
Postoperative renal support 3
Table 3: Descriptive analysis of postoperative complications in the study population (N=9)

Postoperative complications Number

Primary Graft Dysfunction (PGD) grade 3 2
Acute Cellular Rejection – A3 1

Table 4: Summary of Mortality and its causes in the study population (N=9)

Mortality Number
30-day mortality 2
Causes of Mortality (N = 9)  
GNB sepsis 1
Severe PGD 1
Life can be exciting all over again !!!
PPH Pt from Pune – who underwent Heart-Lung Transplant
Successful Bridging with ECMO
Summary
 Outcomes of Transplantation for PAH improving over time
 Lung Transplant vs Heart-Lung Transplant
• Prefer double lung transplant
• Selected patients undergo combined Heart-Lung Transplant
 Deploying ECMO in the setting of PAH
• VA ECMO is means of choice
• ProtekDuo is conceptually ideal, more experience needed
 Early referral and recipient optimization key to transplant outcomes
THANK YOU!
Questions?
Cardiac MRI
Accurate assessment of chamber
size, function, shunts
Cannot replace RHC
RVEDV can enhance risk
assessment
Useful when CHD is suspected
Second line imaging for difficult
cases

Lewis RA, et al. Am J Resp Crit Care Med Feb 2020

Who gets Transplanted ?
- Is a candidate for transplantation
- Referred early enough to have complete evaluation and follow progress /
decline
- Class III even at beginning of treatment
- Highest death rate on transplant waiting list are patients in Class III / Vi dispute
full treatment
- No significant multisystem dysfunction
- Post transplant mortality is significantly higher IF performed in setting of Right
heart failure, Renal dysfunction or Hepatic dysfunction
Who gets Transplanted ?
- NYHA class III or VI functional status
- <50% expected 2-3 year survival
- Intact functional status – 6MWT
- Failing PO/IV therapies
- Cardiac Index <2.2 [<2.0]
- RAP > 15
- Gross RV Dysfunction despite therapy
Which Transplant is the Optimal choice?
- Single Lung Transplant
- Effectively abandoned for Lungs with sustained pHTN (PA pressures > 50-60%
systemic)
- Significantly worse early outcomes
- Pulmonary Edema / Hypoxia
- Ventilation / Perfusion mismatch
- Graft Dysfunction
- Need for additional and prolonged mechanical support
- Still utilized with medically ‘’controlled’’ pHTN in otherwise symptomatic /
Functionally limited patient
Which Transplant is the Optimal choice?
- Double Lung Transplant
- Gold Standard
- Most common surgical treatment option
- Lower incidence of early graft dysfunction
- Mid and Long term remodeling and recovery of RV Function, Improved post Op
PA pressures
- Early outcomes very dependent on actual and recovered function of RV
- Improved short, Mid and Long Term survival
- Markedly lower post Op DAD
- Possible lower / delayed onset of BOS
- Globally improved pulmonary vascular resistance
- Sustained improvement of RV EF
Which Transplant is the Optimal choice?
- Heart-Lung Transplant
- Solves problem of ‘’too sick for transplant’’ or fear of unrecoverable RV Function
- Immediate RV normalization
- Improved airway ischemia, shorter ischemic time
- Matched cardiopulmonary relationship
- Lower long term survival
- Justice in terms of organ allocation and distribution ?. Delay in obtaining all
organs
Which Transplant is the Optimal choice?
- Heart-Lung Transplant
- Congenital heart disease
- Pulmonary hypertension
- Unresponsive or failing in setting of appropriate medical management

--- Paradigm Shift

• Not a candidate for Mechanical bridging

• Failing in setting of Mechanical support
So….
- Should the indications of Heart-Lung Transplant change to :
- Congenital Heart Disease with pHTN
- RV Dysfunction or failure that :
- Cannot be managed with mechanical support
- Unsuccessfully managed with mechanical support
- Should the treatment paradigm change from
- Treat the failing organ to RESCUE and RESUSCITATE the failing organ
Transitional or Rescue Therapy for
significant, symptomatic pHTN pending
transplant
Pre-Transplant Pulmonary support with
RV Recovery and Remodeling
Evidence that pre-emptive Mechanical
support improves post Transplant
outcomes
Conclusion :
- Transplantation while complicated, expensive and limited, remains the gold
standard for end stage pHTN
- Double Lung transplantation is the primary means of surgical treatment
- Heart-Lung transplant continues to have an important role n treatment
- Mechanical means of support will substantially change the use of heart-lung
transplant and likely improve the short and medium term survival.