Heart Transplant:Still the Most Cost Effective and Durable Treatment for

Advanced Heart Failure

Arsalan Shirwany, MD

Stern Cardiovascular Foundation

Baptist Transplant & Mechanical Circulatory Support Center

Clinical Assistant Professor of Medicine

University of Tennessee Health Science Center, Memphis

No relevant financial relationships to disclose

Congestive Heart Failure

• CHF Not one disease entity, rather a syndrome

Many disease processes, sometimes present concurrently

• Inability of heart to meet metabolic demands at normal filling pressure

Increasing prevalence High morbidity and mortality High cost Prognosis worse than most malignancies

CHF: Incidence and Prevalence

• NHLBI Study 5.7 million 2012 prevalence

870,000 new cases annually

• Framingham Data 1 in 5 above 40 will develop HF

• NCHS and NHLBI One in 9 deaths has HF listed on death certificate

~285,000 deaths annually from 1995 to 2011

~50% of patients diagnosed with HF will die within 5 years

Projected US prevalence of HF from 2012 to 2030 is shown for different races.

Heidenreich P A et al. Circ Heart Fail. 2013;6:606-619

Copyright © American Heart Association, Inc. All rights reserved.

CHF: Healthcare Use

• 2000 through 2010: ~1,000,000 hospital discharges

• 2010: 1,800,100 physician office visits

• 2010: 676,000 ER visits

• 2012 HF cost: $30.7 billion

• Projected to increase to $69.7 billion by 2030

The projected increase in direct and indirect costs attributable to HF from 2012 to 2030 is displayed.

Heidenreich P A et al. Circ Heart Fail. 2013;6:606-619

Copyright © American Heart Association, Inc. All rights reserved.

CHF: NYHA Classification

Class Functional Capacity: How patients feel during physical activity

IPatients with cardiac disease but resulting in no limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea or anginal pain.

IIPatients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea or anginal pain.

IIIPatients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain.

IV

Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest.  If any physical activity is undertaken, discomfort increases.

CHF: ACC/AHA Stages

• Stage A: At high risk for HF but without HF symptoms or structual HD

• Stage B: Structural heart disease but no signs or symptoms of HF

• Stage C: Structural heart disease with prior or current symptoms of HF

• Stage D: Refractory HF requiring specialized intervention

Routine    “Annual Heart Failure Review” with a scheduled clinic visitEvent-driven “milestones” that should prompt reassessment    Increased symptom burden and/or decreased quality of life    Significant decrease in functional capacity        Loss of ADLs        Falls

        Transition in living situation (independent to assisted or LTC)

    Worsening HF: hospitalization, particularly if recurrent

    Serial increases of maintenance diuretic dose

    Symptomatic hypotension, azotemia, or refractory fluid retention

        Circulatory-renal limitations to ACEI/ARB

        Decrease or discontinuation of β-blockers because of hypotension

    First or recurrent ICD shock for VT/VF    Initiation of intravenous inotropic support    Consideration of renal replacement therapy

Circulation: 2012;1251928-1952

CHF: Shared Decision Making

Circulation: 2012;1251928-1952

Transplantation

• Offers symptom relief and improves survival

• Long term survival Improved with

donor selection harvest techniques Immunosuppression Management of risk factors and comorbidities

Transplant: Centers

JHLT. 2014 Oct; 33(10): 975-984

Transplant: Centers

Adult and Pediatric Heart TransplantsAverage Center Volume (Transplants: January 2006 – June 2013)

JHLT. 2014 Oct; 33(10): 996-1008

Trends in heart transplantations, 1975 to 2013.

Mozaffarian D et al. Circulation. 2015;131:e29-e322

Copyright © American Heart Association, Inc. All rights reserved.

Adult Heart TransplantsDiagnosis

2014 For some retransplants diagnosis other than retransplant was reported, so the total percentage of retransplants may be greater.

JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart Transplants Diagnosis by Location and Era

Europe North America Other2014 For some retransplants diagnosis other than retransplant is

reported, so the total percentage of retransplants may be greater.

JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart Transplants % of Patients Bridged with Mechanical Circulatory Support*

(Transplants: January 2000 – December 2012)

* LVAD, RVAD, TAH, ECMO2014JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart Transplants % of Patients Bridged with Mechanical Circulatory Support* by Year

and Device Type

* LVAD, RVAD, TAH, ECMO2014JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart TransplantsRecipient BMI Distribution by Location

(Transplants: January 2006 – June 2013)

2014JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart TransplantsRecipient Diabetes Mellitus Distribution by Location

(Transplants: January 2006 – June 2013)

2014JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart TransplantsRecipient Cigarette History by Location

(Transplants: January 2006 – June 2013)

2014JHLT. 2014 Oct; 33(10): 996-1008

Transplant: Work-Up

• Cardiac: LV/RV Function

Functional Capacity

Hemodynamics

Transplant Work-Up

• Medical Pulmonary status

Renal function

Hematology

Oncology

Infectious Disease

GI

Hepatology

Endocrine

• Psycho-social

• Physical/Dietary/Pharmacy

UNOS Status Criteria

• Status 1 A PA catheter with High Dose Inotropic support

LVAD 30 days post implant- use at discretion, Device Malfunction

IABP, BiVAD present, ECMO

• Status 1 B Home on inotropic support

LVAD (other than 30 days)

Angina- uncontrolled

• Status 2 – out of hospital

• Status 7 - Inactive

Cardiac Transplantation

• Pre

Standard medical care Repeat RHC Functional assessment

Cardiac Transplantation

• Post- Hospital

Standard ICU post op care Medical therapy

Immunosuppression Comorbid conditions Recovery and Rehab Surveillance biopsy

Cardiac Transplantation

• Long term Immunosuppression

Corticosteroids CNI Anti-Proliferative mTOR inhibitors

Comorbid conditions HTN DM Hyperlipidemia

Infection Prophylaxis

Adult Heart TransplantsCumulative Morbidity Rates in Survivors within 1, 5 and 10 Years Post

Transplant (Follow-ups: January 1995 – June 2013)

OutcomeWithin 1 Year

Total N with known

response

Within 5 Years

Total N with known

response

Within 10 Years

Total N with

known response

Hypertension* 71.8% (N = 28,163) 91.7% (N = 13,023) -  

Renal Dysfunction 25.8% (N = 31,118) 51.7% (N = 15,769) 68.1% (N = 5,428)

Abnormal Creatinine ≤ 2.5 mg/dl 17.7%   33.1%   38.5%  

Creatinine > 2.5 mg/dl 6.3%   14.6%   20.0%  

Chronic Dialysis 1.5%   2.9%   6.0%  

Renal Transplant 0.3%   1.1%   3.6%  

Hyperlipidemia* 59.8% (N = 29,413) 87.6% (N = 14,372) -  

Diabetes* 24.8% (N = 31,120) 37.5% (N = 15,458) -  

Cardiac Allograft Vasculopathy 7.8% (N = 28,259) 30.1% (N = 11,511) 49.7% (N = 3,146)

* Data are not available 10 years post transplant

JHLT. 2014 Oct; 33(10): 996-1008

Cardiac Transplantation

• Long term complications Rejection

Cardiac allograft vasculopathy (CAV)

Infections

Chronic Renal insufficiency

Malignancy

Adult Heart Transplants % of Recipients Experiencing Treated Rejection Between

Transplant Discharge and 1-Year Follow-Up by Year

Treated rejection = Recipient was reported to (1) have at least one acute rejection episode that was treated with an anti-rejection agent; or (2) have been hospitalized for rejection.

Adult Heart TransplantsKaplan-Meier Survival by Treatment for Rejection Within 1st Year

(1 Year Follow-ups: January 2005 – June 2011) Conditional on survival to 1 year

All pair-wise comparisons were significant at p < 0.0001 except No rejection vs. Untreated rejection (p = 0.8528)

Treated rejection = Recipient was reported to (1) have at least one acute rejection episode that was treated with an anti-rejection agent; or (2) have been hospitalized for rejection.No rejection = Recipient had (i) no acute rejection episodes and (ii) was reported either as not hospitalized for rejection or did not receive anti-rejection agents.

Heart Transplant: Survival(Transplants: January 1982 – June 2012)

All pair-wise comparisons were significant at p < 0.0001 except 2002-2005 vs. 2006-6/2012 (p = 0.9863).

2014JHLT. 2014 Oct; 33(10): 996-1008

All pair-wise comparisons were significant at p < 0.001 except 1992-2001 vs. 2006-6/2012 (p=0.3066) and 2002-2005 vs. 2006-6/2012 (p=0.0804).

JHLT. 2014 Oct; 33(10): 996-1008

Heart Transplant: Survival(Transplants: January 1982 – June 2012)

Adult Heart TransplantsCause of Death (Deaths: January 1994 – June 2013)

CAUSE OF DEATH 0-30 Days (N = 5,609)

31 Days – 1 Year

(N = 4,800)

>1 Year – 3 Years

(N = 3,511)

>3 Years – 5 Years

(N = 3,085)

>5 Years –10 Years

(N = 7,717)

>10 Years – 15 Years (N = 5,186)

>15 Years (N = 2,959)

Cardiac Allograft Vasculopathy 81 (1.4%) 176 (3.7%) 423 (12.0%) 427 (13.8%) 1,055 (13.7%) 706 (13.6%) 345 (11.7%)

Acute Rejection 256 (4.6%) 457 (9.5%) 357 (10.2%) 149 (4.8%) 149 (1.9%) 47 (0.9%) 18 (0.6%)

Lymphoma 3 (0.1%) 57 (1.2%) 84 (2.4%) 104 (3.4%) 286 (3.7%) 154 (3.0%) 75 (2.5%)

Malignancy, Other 2 (0.0%) 117 (2.4%) 424 (12.1%) 592 (19.2%) 1,633 (21.2%) 1,090 (21.0%) 568 (19.2%)

CMV 3 (0.1%) 51 (1.1%) 17 (0.5%) 6 (0.2%) 7 (0.1%) 3 (0.1%) 0

Infection, Non-CMV 713 (12.7%) 1,470 (30.6%) 432 (12.3%) 311 (10.1%) 813 (10.5%) 538 (10.4%) 333 (11.3%)

Graft Failure 2,186 (39.0%) 827 (17.2%) 914 (26.0%) 695 (22.5%) 1,406 (18.2%) 885 (17.1%) 487 (16.5%)

Technical 411 (7.3%) 74 (1.5%) 24 (0.7%) 26 (0.8%) 89 (1.2%) 67 (1.3%) 40 (1.4%)

Other 330 (5.9%) 340 (7.1%) 288 (8.2%) 245 (7.9%) 627 (8.1%) 355 (6.8%) 247 (8.3%)

Multiple Organ Failure 1,010 (18.0%) 746 (15.5%) 213 (6.1%) 191 (6.2%) 531 (6.9%) 429 (8.3%) 272 (9.2%)

Renal Failure 30 (0.5%) 48 (1.0%) 53 (1.5%) 94 (3.0%) 438 (5.7%) 433 (8.3%) 291 (9.8%)

Pulmonary 167 (3.0%) 186 (3.9%) 142 (4.0%) 143 (4.6%) 335 (4.3%) 221 (4.3%) 137 (4.6%)

Cerebrovascular 417 (7.4%) 251 (5.2%) 140 (4.0%) 102 (3.3%) 348 (4.5%) 258 (5.0%) 146 (4.9%)

Total Deaths (N) 6,363 5,481 4,222 3,781 9,534 6,679 3,874

Percentages represent % of deaths in the respective time period. Total number of deaths includes deaths with unknown causes.

JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart Transplants Relative Incidence of Leading Causes of Death

(Deaths: January 1994 – June 2012)

Transplant: Cost-effective?

• Expensive Work-up

Surgery

Follow-up Medications Surveillance testing

Labs Diagnostic imaging Cath, biopsy Complications

• Difficult to estimate

Decision-analytic model diagram for treatment of end-stage heart failure.

Long E F et al. Circ Heart Fail. 2014;7:470-478

Model-projected survival during 5 years.

Long E F et al. Circ Heart Fail. 2014;7:470-478

Copyright © American Heart Association, Inc. All rights reserved.

Cost-effectiveness of end-stage heart failure therapy options.

Long E F et al. Circ Heart Fail. 2014;7:470-478

Copyright © American Heart Association, Inc. All rights reserved.

Transplant: Summary

• Advance Heart Failure Affects ~10% of patients with CHF

Associated with high mortality- more than 50% at one year, close to 80% at two years

• Cardiac Transplant Offers symptom relief

Much longer survival: life expectancy of 8.5 yrs vs 1.1 yr

Average cost ~$97000 per Quality adjusted life year