Lung Transplantation and Concomitant Cardiac Surgery: Is It

Justified?Reshma Biniwale, M.D.Division of Cardiothoracic Surgery

David Geffen School of Medicine, UCLA

Disclosure Statement

No relevant financial relationships to disclose

I will NOT discuss off label use and/or investigational use of any drugs/devices.

Study Introduction

• To determine whether early and midterm clinical outcomes of patients who undergo concomitant cardiac surgery at the time of lung transplant are equivalent to those who undergo isolated lung transplantation.

• 620 total Lung Transplant patients identified from 2000-2013o 120 CCS patients (Lung Transplant + concomitant

cardiac surgery)o Matched cohort of 120 Controls (isolated Lung

Transplant)o Criteria: Recipient Age, Era, Diagnosis, Type of

procedure

Study Inclusion Algorithm

620 Lung Transplant Procedures

500 Isolated Lung Transplant

Procedures

Matched Based on Recipient Age, Era, Diagnosis, Lung Allocation Score, and Type of Procedure

120 Lung Transplant

Procedures and CCS

120 Isolated Lung Transplant Procedures

Study design and Methods• Exclusion criteria: age<18 years, multivisceral

transplant, decreased LV function, diffuse coronary artery disease, age>70years with concomitant cardiac disease, multiple C/I

• Inclusion criteria: repairable cardiac disease, redo recipient (25/620)

• The Kruskal-Wallis rank test was used for comparisons of continuous variables between groups, while the χ2 test was used for categorical variables. Patient survival was determined using Kaplan-Meier analysis; log-rank analysis was utilized for comparisons.

Study Endpoints

• Primary Endpoint: 5-year patient survival

• Secondary Endpoints1) post-operative clinical outcomes:

primary graft dysfunction Grade III at 72 hours, ICU and hospital length of stay

2) 5-year major adverse cardiac events (MACCE)

Incidence of Concomitant Cardiac Surgery in Lung Transplant Recipients in 4 Years Intervals

2000-2004 2005-2009 2010-20130.0%

5.0%

10.0%

15.0%

20.0%

25.0%

17.1%18.3%

21.7%

Incidence of Concomitant Cardiac Surgery

CCS

Donor DemographicsVariables Control

Group(N=120)

CCS Group(N=120)

P-value

Age (years) 38.0 ± 15.0 32.4 ± 14.6 0.013*

Male Sex 76 (59.4%) 81 (63.3%) 0.662

Body Mass Index (kg/m2) 30.4 ± 13.7 26.2 ± 11.1 0.032*

Diabetes mellitus 11 (9.3%) 5 (4.3%) 0.203

Cytomegalovirus positive

77 (67.5%) 74 (67.3%) 0.966

Smoking History 48 (46.2%) 40 (38.8%) 0.287

Donor PaO2 at 100% FiO2 443.4 ± 105.0 452.3 ± 111.8 0.572

Cause of Death: 0.055

Anoxia 17 (14.3%) 16 (13.7%) -

Cerebrovascular accident

55 (35.3%) 34 (29.1%) -

Central Nervous System Tumor

0 (0%) 1 (0.9%) -

Head Trauma 42 (35.3%) 60 (51.3%) -

Other 5 (4.2%) 6 (5.1%) -

Recipient Demographics

Variables Control Group(N=120)

CCS Group(N=120)

P-value

Age (years) 56.7 ± 10.3 56.6 ± 11.3 0.624

Male Sex 79 (59.8%) 72 (54.6%) 0.350

Body Mass Index (kg/m2)

24.9 ± 4.4 25.3 ± 4.3 0.584

Diabetes mellitus 22 (18.3%) 17 (14.2%) 0.382

Systemic Hypertension 40 (33.6%) 36 (30.0%) 0.549

Cytomegalovirus positive

81 (67.5%) 76 (63.3%) 0.497

6-minute walk test (ft) 418.6 ± 455.7 406.5 ± 334.2 0.546

Diagnosis: 0.025*

Obstructive Lung Disease

31 (25.8%) 24 (20%) -

Restrictive Lung Disease

80 (66.7%) 78 (65%) -

Cystic Fibrosis 7 (5.8%) 5 (4.2%) -

Primary Pulmonary Hypertension

2 (1.7%) 13 (10.8%) -

Lung Allocation Score 49.2 ± 17.4 46.8 ± 14.6 0.610

Wait Time (days) 170.1 ± 229.1 157.5 ± 188.7 0.803

Transplant Characteristics

Variables Control Group

(N=120)

CCS Group(N=120)

P-value

Type of Transplant: 0.826

Single, Right 16 (13.3%) 15 (12.5%) -

Single, Left 19 (15.8%) 16 (13.3%) -

Double 85 (70.8%) 89 (74.2%) -

Gender Mismatch 36 (30.0%) 36 (30.0%) 0.931

Cytomegalovirus Mismatch 51 (44.7%) 50 (45.5%) 0.914

Number performed on Cardiopulmonary Bypass

90 (75%) 113 (94.2%) < 0.001*

Cardiopulmonary Bypass Time (min)

148.2 ± 102.5

193.3 ± 81.0

< 0.001*

Allograft Ischemia Time (min) 303.2 ± 82.7 326.3 ± 81.7

0.030*

Aortic Cross-Clamp Time (min) - 32.8 ± 32.7 -

Transplant Characteristics

Variables CCS Group

(N=120)

Concomitant Cardiac Procedures:

CABG x 1 17 (14.2%)

CABG x 2 4 (3.3%)

CABG x 3 1 (0.8%)

Patent Foramen Ovale Repair 66 (55.0%)

Tricuspid Valve Repair 34 (28.3%)

Mitral Valve Repair 2 (1.7%)

Pulmonic Valve Repair 1 (0.8%)

Aortic Valve Repair 2 (1.7%)

Modified Maze Procedure 16 (13.3%)

Left Atrial Appendage Ligation

6 (5%)

Ascending Aortic Aneurysm Repair

2 (1.7%)

Removal of Right Atrial Mass 1 (0.8%)

Multiple Cardiac Procedures 29 (24.2%)

CABGx1

CABGx2

CABGx3

PFO Repair

TV Repair

MV Repair

PV Repair

AoV Repair

MAZE

LAA Ligation AAA Repair RAM Removal

CCS Group

PFO – patent foramen ovaleTV – tricuspid valve MV – mitral valveAoV – aortic valve PV – pulmonic valveLAA – left atrial appendageAAA – ascending aortic aneurysmRAM – right atrial mass

Perioperative Clinical Outcomes

Variables Control Group

(N=120)

CCS Group(N=120)

P-value

Median Duration of Invasive Mechanical Ventilation (days)

2 (1-3) 2 (1-4) 0.110

Re-exploration for bleeding 10 (8.3%) 17 (12.9%) 0.153

Operative wound revision 2 (1.7%) 2 (1.7%) 1.0

Postoperative ECMO 3 (2.5%) 3 (2.5%) 1.0

PGD Grade III @ 72 hours 11 (9.6%) 10 (9.3%) 0.956

Intensive Care Unit Stay (days)

6.3 ± 7.6 8.1 ± 18.9 0.423

Hospital Length of Stay (days) 21.0 ± 17.2 26.0 ± 34.6 0.276

30-Day or In-Hospital Mortality

5 (4.2%) 1 (0.8%) 0.098

In-Hospital Cardiac Complications:

Atrial Fibrillation 26 (21.7%) 25 (18.9%) 0.875

Myocardial Infarction 0 (0%) 0 (0%) 1.0

Cerebrovascular accident 0 (0%) 0 (0%) 1.0

Major Adverse Cardiac Events up to 5-years Post-transplant

Variables Control Group

(N=120)

CCS Group(N=120)

P-value

Major Adverse Cardiac Events

5 (5.3%) 6 (5.0%) 0.758

Atrial Fibrillation 4 (2.5%) 5 (3.8%) 0.734

Operative wound revision 0 (0%) 1 (0.8%) 0.316

Redo Revascularization 0 (0%) 1 (0.8%) 0.316

Redo Valve Procedure 0 (0%) 0 (0%) 1.0

Congestive Heart Failure 0 (0%) 1 (0.8%) 0.316

Pulmonary Embolism 1 (0.8%) 0 (0%) 0.316

Survival Curves of Lung Transplantation Recipients with and without Concomitant

Cardiac Surgery

50% for CCS

55% for Control

Subgroup Analysis I

Kaplan-Meier Survival by Type of CCS Procedure(CABG vs. Other)

Subgroup Analysis II

Kaplan-Meier Survival by Age of Recipients(Transplants: August 2000 – August 2013)

Subgroup Analysis III

Kaplan-Meier Survival by Age of CCS Recipients(Age < 65 vs. Age ≥ 65)

Limitations

• Single institution, retrospective• Mean follow up 6.6 years• No data on patients evaluated for lung transplant who were

not acceptable candidates• QOL data not analyzed

Conclusions

• Similar early and midterm clinical outcomes can be achieved in patients who undergo concomitant cardiac surgery at the time of lung transplantation as compared to isolated lung transplant recipients

• Offering lung transplantation to a highly selected group of patients who need concomitant cardiac surgery may be justified

• Continued expansion of the recipient pool needs to weighed against a limited supply of donor organs

Acknowledgment

Co-Authors:David Ross, M.D.Amit Iyengar, M.S.Oh Jin Kwon, B.S.Curtis Hunter, M.D.Jamil Aboulhosn, M.D.David Gjertson, Ph.D.Abbas Ardehali, M.D.

Division of Cardiothoracic Surgery:Murray Kwon M.D.Ahmad Khan M.D.Richard J. Shemin M.D.

Division of Pulmonology:Joseph Lynch III, M.D.Rajan Saggar, M.D.David Sayah, M.D.Michael Shino, M.D.Sam Weigt, M.D. John Belperio, M.D.Ariss Derhovanessian, M.D.

Division of Cardiology:Jamil Aboulhosn, M.D.Olcay Aksoy, M.D.Eric Yang, M.D.

Recipient Pre-Operative Right Heart Catherization Values

Variables Control Group(N=120)

CCS Group(N=120)

P-value

Systolic Pulmonary Arterial Pressure

(mmHg)

42.5 ± 16.2 51.0 ± 20.7 0.001*

Diastolic Pulmonary Arterial Pressure

(mmHg)

18.4 ± 8.8 21.9 ± 10.5 0.009*

Mean Pulmonary Arterial Pressure

(mmHg)

30.5 ± 12.5 41.3 ± 16.7 <0.001*

Pulmonary Vascular Resistance (dynes/cm5)

310.8 ± 244.0

498.3 ± 373.3 <0.001*

Cardiac Output (L/min) 5.2 ± 1.2 5.2 ± 1.3 0.975

Cardiac Index (L/min/m2)

2.9 ± 0.7 2.8 ± 0.7 0.451