Palliatieve zorg bij hartfalen Dr. G. Ziere klinisch geriater klinisch epidemioloog Symptomen Vermoeidheid Pijn Angst Gebrek aan energie Depressiviteit Dyspnoe Slaperigheid Verlies van eetlust Misselijkheid Cognitieve beperkingen Etiologie 1 • Complex en nog niet volledig begrepen • Meeste patiënten tonen toename van dyspnoe met episodes van ‘volume overload’ – Niet direct gerelateerd aan wiggedruk of cardiac output – Meer systemische effecten met gegeneralizeerde myopathie. • Overlap met comorbiditeit • Symptomen significant versterkt door depressie en door gevoel van controleverlies Het renine-angiotensine-aldosteron systeem Etiologie 2 • Veranderingen in RAAS en andere hormonale systemen – Resulteren in katabole toestand • Activatie van proinflammatoire cytokines – insuline resistentie, cachexie en anorexie • Dragen weer bij aan de katabole toestand ! • Spierveranderingen bij HF zijn vergelijkbaar met afwijkingen gezien bij “sarcopenia of aging” Goodlin, J Am Coll Cardiol 2009;54(5): 386-‐396. Biomarkers for Risk Prediction in Acute Decompensated Heart Failure Curr Heart Fail Rep (2014) 11:246–259 TNF superfamily • TNF is member of a large group of structurally and functionally related cytokines. – At present, the TNFSF comprises over 20 different ligands that mediate their cellular response through more than 30 receptors constituting the TNFRSF. ! • While the TNFSF ligands are normally predominantly expressed by cells in the immune system, the TNFRSF is expressed by a wide variety of cells. – several of these molecules are expressed in cardiomyocytes, fibroblasts, endothelial cells, and vascular smooth muscle cells (SMC) ! • • TNF/TNF Receptor Superfamily Signaling Mediate their effects through two principal classes of cytoplasmic adaptor proteins: – TNFR-‐associated factors (TRAFs) (E.G promoting atherosclerosis) – “death domain” (DD) molecules, ultimately causing caspase activation and apoptosis • TNF-‐related apoptosis-‐inducing ligand (TRAIL) Proposed model for the effects of the OPG/RANKL/RANK axis in HF. Activated T cells may stimulate the receptor RANK of (1) cardiomyocytes or (2) fibroblasts present in myocardial tissue. Production of OPG, binding membrane-‐bound or soluble RANKL and thereby binding to RANK. (3) OPG may interact with TRAIL and protect cardiomyocytes from TRAIL-‐induced cell death. (4) Activated T-‐cells also produce IL-‐17 that can stimulate the production of OPG/RANKL/RANK in fibroblasts and in turn stimulate neighboring fibroblast comprising (5) an autocrine/paracrine loop. (6) Upon stimulation with RANKL, both cardiomyocytes and fibroblasts may produce MMPs (matrix metallo proteinases) that may regulate collagen degradation. Disruption of this collagen network may lead to myocyte slippage, ventricular dilation, and progressive contractile dysfunction Designing new treatment strategies in HF ? • However, these mediators may mediate both adaptive and maladaptive effects on the myocardium. ! • TNFα has been shown to be protective in models of cardiac injury through their ability to activate NF-‐κB, a transcription factor regulating not only inflammation, but also the expression of antiapoptotic and cytoprotective genes. ! • Thus, while too much TNF may be harmful, too little TNF also may have adverse effects. Neurohormonale activatie • Huidige therapie, • Gericht op symptoom-controle • Verlenging van levensduur ! • Door blokkade van de neurohormonale activatie • En controle van vochtretentie. Medicamenteus • • • • Diuretica ACE remmer of Angiotensine receptor blocker (ARB) ß-blocker Mineralocorticoid receptor antagonist (spironolacton, eplerenone) • Digoxine • Ivabradine ! • Vermijden: – NSAID’s, diltiazem, verapamil, of andere kortwerkende dihydropyridine calcium antagonisen; lithium; corticosteroiden Overige interventies 1 • CPAP bij slaap apnoe en Cheynes-Stokes – gunstig effect op neurohormonale activatie • Nachtelijk O2 • Erythropoetine • Lisdiuretica – neurohormonale activatie! • Opiaten – ventilatie respons, vasodilatatie, – subjectieve dyspnoe afname, analgesie – Morfine(metabolieten), Fentanyl • Antidepressiva – SSRI’s (hypoNa, vochtretentie) TCA’s, – methylfenidaat? (AF) • Benzodiazepines ? Overige Interventies 2 • Educatie: – vocht, zout, R/ intake • • • • • • Reductie overgewicht Vocht , zoutbeperking Jaarlijkse (griep) vaccinatie Stoppen met roken (alcohol beperken) Voldoende rust! Bewegen, wandelen! Nieuwe technieken • Pacemakers • Resynchronization therapy • ICD – implantable cardioverter defibrillator • Harttransplantatie • LV assist devices • Stamceltransplantatie The Medication Appropriateness Index 1. 2. 3. 4. 5. 6. 7. Is there an indication for the drug? Is the medication effective for the condition? Is the dosage correct? Are the directions correct? Are the directions practical? Are there clinically significant drug-drug interactions? Are there clinically significant drug-disease/condition interactions? 8. Is there unnecessary duplication with other drugs? 9. Is the duration of therapy acceptable? 10. Is this drug the least expensive alternative compared with others of equal usefulness? Hanlon et al. J Clin Epidemiol 1992;45(10):1045-‐51. Reconsidering Medication Appropriateness for Patients Late in Life Behandeling hangt af van ▪ Evidence bij ouderen ▪ Biologische leeftijd ▪ Time until benefit van de therapie ▪ Ernst van de bijwerkingen Holmes HM, et al. Arch. Int Med 2006;166(6):605-9. Therapiekeuze: In relatie tot time until benefit, behandel- en zorgdoel Holmes et al. Arch Int Med 2006;166:605-9. Baat tijd en NNT voor pravastatine bij 70-82 jarigen •2 jaar (cardiovasculaire events) •3 jaar secundaire preventie CVA •NNT: cardiale events placebogroep:12,2% pravastatine: 10,1% verschil: 2,1% NNT: 48 Tailored or personalized prescribing Holmes et al. Arch. Int. Med. 2006;166:605-9. Palliatieve zorg Palliatieve zorg bij hartfalen • • • • Ernstig hartfalen heeft een zeer slechte prognose op korte termijn. I.t.t. andere vormen van palliatieve zorg: Én actief blijven behandelen én actief palliatieve zorg blijven geven. 4 aandachtsgebieden – zorg voor lichamelijke, psychische, sociale en spirituele factoren. [WHO 2004] ! • Een palliatief zorgteam kan bestaan uit: – een zorgcoördinator, huisarts, cardioloog, hartfalenverpleegkundige/ praktijkondersteuner, palliatiespecialist, psycholoog/psychotherapeut, fysiotherapeut, diëtist, en geestelijke. ! • De behandeling van de eindfase van hartfalen dient een integraal onderdeel te vormen van hartfalen zorgprogramma‟s [Metra 2007, Goodlin 2004, McKinley 2004]. Multidisciplinaire richtlijn Hartfalen 2010 Optimale behandeling van hartfalen • Ook in de terminale fase een cruciaal onderdeel van de palliatie. • Smalle marge tussen overvulling en ondervulling, kenmerkend voor de eindfase van hartfalen • Vaak keuze van zeer hoge diureticadoseringen – (eventueel combinaties van verschillende diuretica) – Ondervulling met somnolentie door cerebrale hypoperfusie heeft de voorkeur boven dyspneu door overvulling van de longen. Multidisciplinaire richtlijn Hartfalen 2010 Internationale Richtlijnen • ESC Guideline 2012 Acute and chronic HF • Gap of evidence: End-‐of-‐life care – What is the optimum palliative care package? – When should palliative care be started? ! • ACCF/AHA guideline for the management of HF 2013: • Recommendation for Hospital Discharge: – Consideration palliative care or hospice care in selected patients. ACCF/AHA guideline for the management of heart failure. Circulation2013;128(16): 1810-‐1852. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure Eur Heart J 2012;33(14): 1787-‐1847 Aanbeveling RL HF 2010 • Patiënten met ernstig hartfalen en met name als verwacht kan worden dat ze op korte termijn zullen overlijden komen in aanmerking voor gestructureerde palliatieve zorg waarbij ook symptomen van angst en depressie bij de behandeling worden betrokken – bewijsniveau 4 All cause mortality HF Crude mortality per 1000 patient years Men : 137 ( 95% CI 133 – 140 ) Women: 135 ( 95% CI 131 – 139 ) Martinez-‐Selles, M., et al. (2012). Eur J Heart Fail 14(5): 473-‐479. HF from geriatric perspective • First year – mortality after hospitalization can reach 60% in older patients ! • Age distribution among people who died from HF 30 – 40 years old 0,13% 40 – 50 years old 0,67% 50 – 60 years old 5,65% 60 – 70 years old 15,05% 70 – 80 years old 22,04% 80 – 90 years old 48,79% 90 – 100 years old 7,66% HFrEf an HFpEF: The EF is not the only difference Hamaguchi, S., et al. (2012). Circ J 76(7): 1662-‐1669. Hamaguchi, S., et al. (2012). Circ J 76(7): 1662-‐1669. Typisch beloop hartfalen Goodlin, J Am Coll Cardiol 2009;54(5): 386-‐396. Wanneer starten met palliatieve zorg? Dying of lung cancer or cardiac failure: • prospectieve interview studie ! • Patiënten met hartfalen hadden een onvoorspelbaarder ziekte beloop dan het meer lineaire patroon bij patiënten met longkanker. ! • Ze waren ook slechter op de hoogte van hun situatie en prognose en werden minder betrokken bij beleidsbeslissingen. BMJ 2002;325:929 Outline comparison of experience of patients • Lung cancer • Cardiac failure • Gradual decline punctuated by episodes of acute deterioration; sudden, usually unexpected death with no distinct terminal phase • Cancer trajectory with clearer terminal phase; able to plan for death • Initially feel well but told you are ill • Feel ill but told you are well • Good understanding of diagnosis and prognosis • Little understanding of diagnosis and prognosis • "I know it won't get better, but I hope it won't get any worse" • "How long have I got?" • Relatives anxious • Relatives isolated and exhausted • Swinging between hope and despair • Daily grind of hopelessness Outline comparison of experience of patients • Lung cancer • Cardiac failure • Lung cancer takes over life and becomes overriding concern • Much comorbidity to cope with; heart often not seen as main issue • Treatment calendar dominates life, more contact with services and professionals • Shrinking social world dominates life, little contact with health and social services • Feel better on treatment: work of balancing and monitoring in the community • Less access to benefits with uncertain prognosis • Feel worse on treatment: coping with side effects • Financial benefits accessible • Specialist services often available in the community • Specialist services rarely available in the community • Care prioritised early as "cancer" and later as "terminally ill" • Less priority as a "chronic disease" and less priority later as uncertain if yet "terminally ill" Doctors' perceptions of palliative care for heart failure: focus group study • Dokters herkennen en ondersteunen de ontwikkeling van palliatieve zorg. ! • Belemmeringen: – De organisatie van de gezondheidszorg – Het onvoorspelbare beloop van hartfalen – Wat is de rol van de dokter? BMJ 2002;325:581-585 Het beloop van de aandoening • De onzekere prognose leidt tot moeizame overwegingen “wanneer het slechte nieuws te brengen” ! • Het "therapeutisch en anti-therapeutisch" nut van prognosticatie. ! • De grootste zorg bij cardiologen was dat “de verkeerde dingen zeggen” zou leiden tot verlies van vertrouwen in hun dokter, terwijl huisartsen het moeilijk vonden als patiënten de strijd te vroeg zouden opgeven. Voorbeelden • “But even when you're at the very end and it's the last few weeks, you still don't know whether they're going to just die suddenly now or whether over the next few weeks they're just going to gradually drift away. So that does make it more difficult in trying to prepare them and their relatives for what's actually going to happen. (Cardiologist) ! • It's very difficult, you can't really say who's going to recover . . . you know sometimes they respond and sometimes they don't. So it's this sort of roller coaster type of thing and it's very difficult to give a prognosis other than "well it's his heart, it is serious you know." (General practitioner)” Criteria voor palliatie bij ernstig hartfalen • Patiëntkenmerken : • > 1 episode van exacerbatie/6 maanden ondanks optimale therapie • frequente of continue intraveneuze medicatie • cardiale cachexie • terminaal hartfalen 1e lijns richtlijn Palliatieve zorg, Eizenga 2006 SUPPORT Study to Understand Preferences for Outcomes and Risks of Treatments • Ernstige symptomen in de laatste drie dagen bij patiënten met hartfalen: ! • Dyspnoe in 65%, ernstige pijn bij 42%. • Bij 40% nog belangrijke therapeutische interventies in die 3 dagen. ! • Wekt suggestie dat artsen de naderende dood niet hadden opgemerkt. Levenson et al. J. Am. Geriatr. Soc. 2000; 48(5suppl):S101-9 Dying trajectories in heart failure. What this study adds: ! No typical dying trajectory in heart failure was identified, and only a minority of patients conform to the theoretical trajectory underpinning current service developments. Gott, M., et al. (2007). Palliat Med 21(2): 95-‐99. Prognostication • Numerous clinical scoring systems: – NYHA classification – Biochemical markers (BNP) – HF Survival Score (HFSS)—employed in the selection of patients for cardiac transplantation, and the – Seattle HF Score (http://depts.washington.edu/ shfm/) http://depts.washington.edu/shfm/ Man 85 jr Met LVAD Wie krijgen palliatieve zorg? • Retrospective analysis 2006 – 2011 for HF patients referred to Palliative Care consultation • N = 132 ≈ 10% of patients with end-‐stage HF • Mean age = 76 (67 – 82) • Based on Seattle HF Model predicted mean live expectancy was 2.8 years, and real survival in study was 0.06 year! • Median survival 21 days Personal communication P. Sobanski ; EUGMS 2014, Rotterdam Symptoms in outpatients ( NYHA II, III ) after hospitalization for HF Evangelista, L. S., et al. (2014). J Palliat Med 17(1): 75-‐79. Impact of palliative care on symptom intensity in heart failure Evangelista, L. S., et al. (2014). J Palliat Med 17(1): 75-‐79. Effect ICD Frohlich, G. M., et al. (2013). Heart 99(16): 1158-‐1165. The relation between PC and cardiological treatment • Medicare and Medicaid in the US have stipulated that centres implantinng VADs as a destination therapy include a PC specialist as a member of the cardio-‐team, due to the fact that durable mechanical support might significantly alter EoL trajectory http://www.cms.gov/medicare-‐coverage-‐database/details/nca-‐ proposed-‐decision-‐memo.aspx?NCAId=268 End-of-life trajectory and deactivating left ventricular assist device (LVAD) in destination therapy (DT). Rady M Y , and Verheijde J L J Intensive Care Med 2012;29:3-‐12 Conclusie • Neurohumorale activatie is meer dan RAAS alleen. ! • Palliatieve zorg bij hartfalen wordt onderkend. ! • In tegenstelling tot gangbare vormen van palliatieve zorg moet men bij terminaal hartfalen én actief blijven behandelen én actief palliatieve zorg blijven geven. ! • Door onvoorspelbaar beloop is prognosticatie lastig ! • Overweeg multidisciplinaire consultatie bij "mechanische" interventies. 54