VAD or heart transplantation after age 65

VAD or heart transplantation after age 65 Dr. Phyllis Billia MD PhD FRCPC Medical Director Mechanical Circulatory Support Program Peter Munk Cardiac Centre May 11th 2019 Disclosure Slide  Grants/research support: CIHR, Medicine by Design, PMCC Innovation Fund, NSERC-CIHR  Consulting fees: n/a  Speaker fees: n/a  I will NOT discuss off-label uses of drugs Objectives  Review the evidence for advanced HF therapies in older patients  Outcomes with heart transplant in the older population  Outcomes with LVAD  Heart transplant versus LVAD Age-adjusted leading cause of death, US 2009 National Vital Statistics Reports 2011 Naylor et al, ICES 1999 Senni et al, Circ 1998 Lee et al, Circulation 2009 Costanzo MR et al, AHJ 2008 Heidenreich PA et al, Circulation. 2011 Courtesy of Dr. HJ Ross. 50 000 Advanced HF ~ 200 transplants 75 VADs 500,000 with HF diagnosis Advanced therapies Experimental Rx Cardiac replacement Tailored therapy IV Vasodilators IV diuretics Optimization of oral therapy Referral for CRT/ICD Aldosterone antagonist ACEi /ARB, Beta blocker Diet, exercise prescription Risk factor control Chronic Disease Management Konstam, Circulation. 2012 Over the next 20 years: • Prevalence will increase by 25% • Annual direct medical costs will increase $77.7 billion (2008 dollars) Prognostic Markers  General  Age, diabetes, sex, weight (BMI), etiology of HF, comorbidities (COPD, cirrhosis)  Laboratory markers  Na, creatinine (and eGFR), urea, BUN,  Hgb, % lymphocytes,  uric acid  Low HDL  Insulin resistance  Urine  Abluminuria  NGAL - neutrophil gelatinase associated lipocalin  Biomarkers  BNP, NT pro BNP, troponin, CRP, cystatin C, GDF-15 (growth differentiation factor), serum cortisol, TNF, ET, NE, midregional-pro-adrenomedullin (MR-proADM), pro-apoptotic protein apoptosis-stimulating fragment (FAS)  Medication  Intolerance to ACEI, diuretic dose  FC IV  Especially if sustained > 90 days  6 minute walk  Cardiopulmonary markers  Peak VO2, % predicted, VE/VCO2, AT, workload, systolic BP < 130, HR recovery  Clinical Exam markers  BP (admission and discharge), heart rate, JVP, +S3, cachexia  Depression  Obstructive sleep apnea  Echo parameters  EF, chamber size (LV, LA, RA), sphericity,  RNA  RVEF, LVEF  Recurrent hospitalizations  ECG  IVCD  Hemodynamic markers  PA pressures, CO, CI, MVO2  Endomyocardial biopsies  Microarrays transcriptomic biomarkers  Marital status World population pyramids Canada’s Aging Population – The baby boomers 0 5 10 15 20 25 1921 1931 1941 1951 1961 1971 1981 1991 1998 2016 2021 2026 2031 2036 2041 Age: 65 yrs and over % of population >65 yrs old Aging population  US/Canada Statistics  The proportion of the population that is >65 years of age will double in the next 20 years.  Need to understand outcomes in this patient population  It used to be that transplants would only be done patients <50 years of age  Some centers viewed advanced age as a contraindication to consideration of advanced therapies and namely transplantation HF in the real world: Age 75 years Female 52% Hypertension 72% Diabetes 44% Atrial fibrillation 31% COPD 31% Chronic kidney disease 30% What the “average” HFrEF patient looks like Gheorghiade , 2005 Therapeutic Approach to Patients With HFrEF CCS HF guidelines The spectrum of HF ACC/AHA Disease Trajectory NYHA Stage A High risk, no symptoms Stage B Structural disease No symptoms Class I No symptoms INTERMACS Stage C Symptomatic Stage D Refractory symptoms Very advanced HF Class II Limited with activity Class III Limited with less than ordinary activity Class IV Severely limited any activity worsens symptoms Risk of hospitalization for AHF 1 2 3 456 Dilemmas of Transplantation vs LVAD Transplantation  ‘Selective’ patient selection  Not readily available  Limited donor pool  Consequences of immunosuppression LVAD  Driveline exit site  Adverse events  Batteries  Durability of device Transplant (VAD) workup  CPET testing (Class 1B)  RHC (Class 1C) +/- vasodilator challenge  Co-morbidities  Age, BMI <35, cancer, DM, CKD, PVD, tobacco use, substance abuse (?cannabis), psychosocial, frailty  “Carefully selected patients >70 years of age may be considered for cardiac transplantation. For centers considering these patients, the use of an alternate-type program (i.e., use of older donors) may be pursued (Class IIb, Level of Evidence: C).” ISHLT 2016 – listing criteria 10-year update Positives in patients ≥ 70 y.o.  More mature and compliant  less likely to derive a driveline injury (less active)  More accepting of inherent lifestyle limitations presented by LVAD support  Appreciative of the improved quality of life  Have supportive adult children willing to assist in care  Financial stability Precautions in patients ≥ 70 y.o.  Poor eye sight  Decreased manual dexterity  Older care givers  Higher rate of co-morbidities Transplant in older patients Goldstein et al. JHLT.2012 31:679-685 UNOS data – Jan 1998 to June 2010 Defining 2 age groups: 60-69; >70 11,307 patients >60 y.o. (including 445 >70 y.o.) Age distribution of heart transplant recipients Age distribution of heart transplant recipients Cooper et al JHLT 2016 UNOS data – Jan 1987 to June 2014 Defining 2 age groups: 60-69; >70 50,432 patients (including 715 >70 y.o.) UNOS registry Cooper et al JHLT 2016 Goldstein et al. JHLT.2012 31:679-685 Median survival for age > 70 8.5 years UNOS OHT Survival 2005-2013 Age > 70 versus < 70 George. Ann Thorac Surg 2013 ISHLT registry - 30d mortality 64,354 heart transplants, 1988-2013 Estimated effect of donor (A) and recipient (B) age on 30-d mortality Univariant logistic regression model Bergenfledt et al JHLT 2019 Post-transplant survival stratified by age – 10 year follow-up Post-transplant survival stratified by age Conditional post-transplant survival stratified by age Wever-Pinzon et al, JHLT 2017 52,995 recipients – ISHLT registry 1995-2011 Wever-Pinzon et al, JHLT 2017 ISHLT registry captures 65% of all heart transplants performed world-wide Confirmation that age >70 at the time of transplant is associated with increased risk of death Interestingly, at 3 and 5 years post-transplant, fewer patients had different strategies of IS Risk of cause-specific mortality Another way to look at the data Kaplan-Meier survival curves of post-transplant mortality for donor-recipient age 64,354 heart transplants, 1988 – 2013 ISHLT registry Recipient age associated with longer term mortality Older donor age was associated with higher mortality at all f/u time points Bergenfledt et al JHLT 2019 LVAD in older patients Important things to consider Patient Characteristics  Age  Size  Blood type  Hemodynamic stability  Associated illnesses Center Specific Data  Wait times  Adverse events From 2008-2017 – 18,539 patients with LVADs 20% females LVAD implantation – INTERMACs data Kormos et al., JHLT 2019 Based on Intermacs Profile Kirklin et al., JHLT 2011 Age 60 to 70 Hazard ratio for death: 1.78 (p < 0.0001) Age - independent risk factor for DT-LVAD DT-VAD in older patients Nair and Gongora Exp. Rev. Cardiol. 2018 2016 2013 2011 2015 Kim et al J. Card Failure 2016 MCS Research Network - 1149 CF LVADS Thrombosis Stroke SurvivalBleeding Age distribution of LVAD recipients % of older patients getting LVAD Survival post-LVAD Kim et al J. Card Failure 2016  Advanced age as a dichotomized variable around age 70 is not a significant independent predictor of survival  When age is set as a continuous variable – predicts mortality with a 20% increase risk of death/10 years of life.  Known that age is a strong predictor of GIB – age >65 associated with a 20-fold increased risk  GIB is associated with increase risk for thromboembolic events  The most significant independent predictor of survival was creatinine  There is a 2-fold higher risk of death for every 0.1 mg/dL increase in creatinine Kirklin et al., JHLT 2013 Age as an independent risk factor for death among LVAD recipients Freedom from adverse events after LVAD stratified by age Community experience Adamsom et al., JACC 2011 No significant differences in survival, LOS, functional status improvement or adverse events (55 patients). Pre-operative risk factors for outcomes Boyle et al 2014  Retrospective  Patients with HMII as part of DT or BTT clinical trials  2005 – 2010  1,302 patients (956 patients included in the analysis)  2 years follow-up Effects of Gender and Age Boyle et al, JACC 2014 Older age, and its associated risk of GIB has been well documented. This analysis showed older patients were at a higher risk of: • bleeding events • female gender • anemia before surgery • risk of stroke (females) LVAD vs Transplant LVAD vs OHT Abstract - Melnitchouk et al., JHLT 2011 Single centre – Columbia • 19 LVAD vs 28 OHT • LVAD patients were older (72yo vs 68 yo) • 1year survival similar • LVAD group had a longer ICU and total length of stay Survival: HeartMate II vs Transplant 42 Months 0 6 12 18 24 30 36 Survival (%) 0 10 20 30 40 50 60 70 80 90 100 Age < 70 (N=122) Age >=70 (N=74) 81±4% 70±5% 56±6% 79±5% 70±6% 56±7% p=0.959 Adamson et al., 2011; unpublished INTERMACs – Cumulative incidence post-VAD mortality post-VAD transplantation post-VAD recovery Aleksova et al, unpublished data 2019 Complications post-VAD Adverse event type Cause-specific HR for age of 70 or above [95% CI] P-value GI bleeding 1.200 [1.089, 1.322] <0.001 Infection 0.962 [0.886, 1.044] 0.35 Stroke 0.858 [0.741, 0.992] 0.039 Pump-related thrombosis 1.247 [0.408, 3.813] 0.70 Pump exchange 0.683 [0.562, 0.830] <0.001 Right heart failure 0.690 [0.532, 0.894] 0.005 Pump exchange Right heart failure Aleksova et al, unpublished data 2019 Things to consider  Older patient population is growing.  Heart failure is an epidemic associated with a need to consider advanced therapies in older patients.  Heart transplantation is resource limited.  Age does affect outcomes post-transplant (median survival 8.5 years, age >70 y.o.)  DT-LVAD numbers are growing  LVAD outcomes is affected by age but patients >70 y.o. do well BUT we have VAD-related complications to consider Conclusions “Aging” does not equate to being frail nor does youth guarantee good health. “Chronologic Age” cannot be a strict discriminator for patients that need advanced therapies. The decision regarding “older patients “ should be made with careful consideration. It is still unknown whether age-based treatment policies in primary/secondary care reflect prejudices against older people. Questions?