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

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

Patients 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.

Patients 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.

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

CHF: Shared Decision Making

Routine “Annual Heart Failure Review” with a scheduled clinic visit Event-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

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 Transplants

Average 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 Transplants

Diagnosis 2014 JHLT. 2014 Oct; 33(10): 996-1008 For some retransplants diagnosis other than retransplant was reported, so the total percentage of retransplants may be greater.

Adult Heart Transplants

Diagnosis by Location and Era Europe 2014 North America Other 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) 2014 JHLT. 2014 Oct; 33(10): 996-1008 * LVAD, RVAD, TAH, ECMO

Adult Heart Transplants

% of Patients Bridged with Mechanical Circulatory Support* by Year and Device Type 2014 JHLT. 2014 Oct; 33(10): 996-1008 * LVAD, RVAD, TAH, ECMO

Adult Heart Transplants

Recipient BMI Distribution by Location (Transplants: January 2006 – June 2013) 2014 JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart Transplants

Recipient Diabetes Mellitus Distribution by Location (Transplants: January 2006 – June 2013) 2014 JHLT. 2014 Oct; 33(10): 996-1008

Adult Heart Transplants

Recipient Cigarette History by Location (Transplants: January 2006 – June 2013) 2014 JHLT. 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 Transplants

Cumulative Morbidity Rates in Survivors within 1, 5 and 10 Years Post Transplant (Follow-ups: January 1995 – June 2013) Outcome Hypertension* Renal Dysfunction

Abnormal Creatinine ≤ 2.5 mg/dl Creatinine > 2.5 mg/dl Chronic Dialysis Renal Transplant

Hyperlipidemia* Diabetes* Cardiac Allograft Vasculopathy Within 1 Year Total N with known response 71.8% (N = 28,163) 25.8% (N = 31,118)

17.7% 6.3% 1.5% 0.3%

59.8% (N = 29,413) Within 5 Years 91.7% Total N with known response (N = 13,023) 51.7% (N = 15,769)

33.1% 14.6% 2.9% 1.1%

87.6% (N = 14,372) Within 10 Years Total N with known response 68.1%

38.5% 20.0% 6.0% 3.6%

(N = 5,428) 24.8% 7.8% (N = 31,120) (N = 28,259) 37.5% 30.1% (N = 15,458) (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 Transplants

Kaplan-Meier Survival by Treatment for Rejection Within 1 st (1 Year Follow-ups: January 2005 – June 2011) Conditional on survival to 1 year 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). 2014 JHLT. 2014 Oct; 33(10): 996-1008

Heart Transplant: Survival

(Transplants: January 1982 – June 2012) 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

Adult Heart Transplants

Cause of Death (Deaths: January 1994 – June 2013) CAUSE OF DEATH Cardiac Allograft Vasculopathy Acute Rejection Lymphoma 0-30 Days (N = 5,609) 81 (1.4%) 256 (4.6%) 3 (0.1%) 31 Days – 1 Year (N = 4,800) 176 (3.7%) 457 (9.5%) 57 (1.2%) >1 Year – 3 Years (N = 3,511) 423 (12.0%) 357 (10.2%) 84 (2.4%) Malignancy, Other CMV 2 (0.0%) 3 (0.1%) 117 (2.4%) 51 (1.1%) 424 (12.1%) 17 (0.5%) Infection, Non-CMV Graft Failure Technical Other 713 (12.7%) 2,186 (39.0%) 827 (17.2%) 411 (7.3%) 330 (5.9%) 1,470 (30.6%) 74 (1.5%) 340 (7.1%) Multiple Organ Failure Renal Failure Pulmonary Cerebrovascular Total Deaths (N) 1,010 (18.0%) 746 (15.5%) 30 (0.5%) 167 (3.0%) 417 (7.4%) 6,363 48 (1.0%) 186 (3.9%) 251 (5.2%) 5,481 432 (12.3%) 914 (26.0%) 24 (0.7%) 288 (8.2%) 213 (6.1%) 53 (1.5%) 142 (4.0%) 140 (4.0%) 4,222 >3 Years – 5 Years (N = 3,085) 427 (13.8%) >5 Years – 10 Years (N = 7,717) 1,055 (13.7%) >10 Years – 15 Years (N = 5,186) 706 (13.6%) >15 Years (N = 2,959) 345 (11.7%) 149 (4.8%) 104 (3.4%) 26 (0.8%) 245 (7.9%) 191 (6.2%) 149 (1.9%) 286 (3.7%) 89 (1.2%) 627 (8.1%) 531 (6.9%) 47 (0.9%) 154 (3.0%) 67 (1.3%) 355 (6.8%) 429 (8.3%) 18 (0.6%) 75 (2.5%) 592 (19.2%) 1,633 (21.2%) 1,090 (21.0%) 6 (0.2%) 7 (0.1%) 3 (0.1%) 311 (10.1%) 695 (22.5%) 813 (10.5%) 1,406 (18.2%) 538 (10.4%) 885 (17.1%) 568 (19.2%) 0 333 (11.3%) 487 (16.5%) 40 (1.4%) 247 (8.3%) 272 (9.2%) 94 (3.0%) 143 (4.6%) 102 (3.3%) 3,781 438 (5.7%) 335 (4.3%) 348 (4.5%) 9,534 433 (8.3%) 221 (4.3%) 258 (5.0%) 6,679 291 (9.8%) 137 (4.6%) 146 (4.9%) 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