Heart Failure Update Michael Fu Professor, Överläkare
Update in Diagnosis Update in Pharmacological Treatment Update in Device Therapy Heart Failure in the Elderly Put Guidelines into Clinical Practice
Update in Diagnosis
The very essence of cardiovascular medicine is the recognition of early heart failure Sir Thomas Lewis 1933
Definition of heart failure Symptom typical of HF + Signs typical of HF + Objective evidence of a structural or functional abnormalty of the heart at rest (cardiomegaly, 3rd heart sound, murmurs, abnormalty on echo, raised natriuretic peptide)
BNP Brain Natriuretic Peptide B type Natriuretic Peptide
BNP/NTpro BNP Ett fönster för hjärtas hemodynamik
Skillnad mellan BNP och NTpro BNP BNP NT-proBNP Aminosyror 32 76 MV 3500 8500 Biologiskt aktiv ja nej Halveringstid (min) 20 60-120 Analysmetod Bedside Ja Ja Central-Lab Nej Ja Känslighet Ngt mer vid lindrig hjärtsvikt Eliminering Neutral peptidase Njur
Så länge BNP resp NTpro BNP analyseras korrekt! BNP Likvärdig NTpro-BNP
Evidence
Dokainish et al: Circulation 2004, 109(20): 2432-
Systolisk svikt Diastolisk svikt LVEF BNP NTpro BNP
ESC guideline 2008 Clinical examination, ECG, Chest X-ray Natriuretic peptides BNP <100 NTpro BNP <400 BNP 100-400 NTpro BNP 400-2000 BNP >400 NTpro BNP >2000 CHF unlikely CHF uncertain CHF likely
Update in Pharmacological Treatment
ESC guideline 2008 Objectives of treatment of chronic heart failure Prognosis Life quality Morbidity Prevention
Farmaka vid hjärtsvikt Βeta-adrenerga receptor blokerare (Beta-blokerare) ACE hämmare Aldosteron receptor antagonist Angiotensin receptor blokerare (AT1 blokerare) Digitalis Diuretika Antikoagulation Vasodilaterare Antiarytmika Inotropa Kalcium kanal blokerare Statin ASA
Evidence based step by step medications Class II Class III Class IV ß blocker ACE inhibitor ß blocker ACE inhibitor ARB ß blocker ACE inhibitor ARB Spironolacton
Symptomatic CHF ACEI+BB Yes Persisting symptoms & sign NO ARB or Aldosterone antagonist Persisting symptoms Yes NO LVEF<35% Yes QRS>120 ms CRT/CRT-D Yes ICD
Symptomatic CHF ACEI+BB ACEI intolerance ARB VILKA?
Mortality Survival Event-free Survival CV Death or HF Hosp 1.0 Val-HeFT.5 CHARM-Alternative Placebo Valsartan 320mg Placebo Candesartan 32 mg.6.3 Cohn et al: NEJM 2001 VALIANT Valsartan 320 mg 27 mos Captopril 150 mg 0 1.0 Granger et al: Lancet 2003 ELITE-2 Losartan 50 mg 42 mos Captopril 150 mg 0 Pfeffer et al. NEJM 2003 Pitt B et al: Lancet 2000 0 36 mos 23 mos
Comparison of Low-Dose Versus High-Dose Losartan Treatment on Morbidity and Mortality in Angiotensin-Converting-Enzyme-Inhibitor- Intolerant Patients with Heart Failure and Reduced Left Ventricular Ejection Fraction: Results of the HEAAL* Study Marvin A. Konstam, James D. Neaton, Kenneth Dickstein, Helmut Drexler, Michel Komajda, Felipe A. Martinez, Gunter A.J. Riegger, Ronald D. Smith, William Malbecq, Soneil Guptha, Philip A. Poole- Wilson for the HEAAL investigators Lancet 2009; 374: 1840 48
Dedication
% of Patients with First Event Percentage of patients with first event Death or Hospitalization for HF 50 Losartan 50 mg Losartan 150 mg 40 HR 0.90 (0.82, 0.99) Hazard ratio: 0.90, p=0.027 P=0.027 30 20 Note! Losartan 150 mg 10 0 Losartan 50 mg 0 1 2 3 4 5 Number of patients at risk Losartan 150 mg 1646 1421 1422 1275 1277 1126 644 1683 1492 Years 1343 1205 1684 1493 1344 1205 711 Konstam MA et al, Lancet 2009; 374: 1840 48 711
ARB Indication no. 1 Vid ACE inhibitor intolerance Candesartan (Atacand) Valsartan (Diovan) Losartan * endast 150 mg
Symptomatic CHF ACEI+BB Yes Persisting symptoms & sign NO ARB or Aldosterone antagonist VILKEN?
As add-on ARB or Aldosteron antagonist?
ARB Indication no. 2 Add-on treatment (on top of ACEI)
Behandling med ARB Kandesartan Valsartan Startdos (mg) 4-8 x 1 20 x 2 Måldos (mg) 32 x 1 160 x 2 Måldos eftersträvas. Dosdubblering varje till varannan vecka. Kontroll av s-kreatinin och s-kalium. 51
CHARM Programme
CHARM-Added Primary outcome, CV death or CHF hospitalisation % 50 40 Placebo 538 (42.3%) 483 (37.9%) 30 Candesartan 20 10 Number at risk 0 HR 0.85 (95% CI 0.75-0.96), p=0.011 Adjusted HR 0.85, p=0.010 0 1 2 3 3.5 years Candesartan 1276 1176 1063 948 457 Placebo 1272 1136 1013 906 422 McMurray et al, Lancet 2003
Aldosteron antagonist
Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms EMPHASIS-HF* Faiez Zannad, M.D., Ph.D., John J.V. McMurray, M.D., Henry Krum, M.B., PhD., Dirk J. van Veldhuisen, M.D.,Ph.D., Karl Swedberg, M.D., Ph.D, Harry Shi, M.S., John Vincent, M.B., PhD., Stuart J Pocock, Ph.D. and Bertram Pitt, M.D. for the EMPHASIS-HF Study Group ClinicalTrials.gov, NCT00232180 * Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure
1.00 0.90 0.80 0.70 0.60 0.50 0.40 Mineralocorticoid Receptor Antagonists (MRAs) in Heart Failure Survival 30% RR, P < 0.001 Spironolactone 0 6 12 18 24 30 36 Months HYPOTHESIS: 20 0 0 6 Total Mortality 15% RR, P=0.008 Placebo 12 18 Months Eplerenone Eplerenone, added to evidence-based therapy, is 10 associated with improved clinical outcomes in patients Placebo with systolic heart failure and mild symptoms 24 30 36 RALES (LVSD, CHF severe symptoms) Pitt B, Zannad F, Remme WJ, et al. N Engl J Med. 1999 EPHESUS (LVSD + HF after MI) Pitt B, Remme W, Zannad F, et al. N Engl J Med. 2003
Study Design and Sample Size 25 mg Eplerenone 50 mg qd 25 mg Placebo 50 mg qd Screen Randomization 1 Month 3 Months Follow-up Primary endpoint: CV death or hospitalization for HF Zannad et al N Engl Med 2011;364:11-21
Primary Endpoint: Cumulative K-M Rate (%) Primary Endpoint Cardiovascular Death or Hospitalization for HF 50 40 30 20 HR [95% CI] = 0.63 [0.54, 0.74] P < 0.0001 Placebo 356 (25.9) Eplerenone 249 (18.3) RRR; 37% ARR; 7,6% 10 0 0 1 2 3 No. at Risk Years from Randomization Placebo 1373 848 512 199 Eplerenone 1364 925 562 232 *Unadjusted HR 0.66; 0.56, 0.78; p<0.0001 Zannad et al N Engl Med 2011;364:11
All-Cause Mortality: Cumulative K-M Rate (%) Mortality From Any Cause 40 30 HR [95% CI] = 0.76 [0.62, 0.93] P = 0.0081 Placebo 213 (15.5) RRR;24% ARR; 3% 20 Eplerenone 171 (12.5) 10 0 0 1 2 3 No. at Risk Years from Randomization Placebo 1373 947 587 242 Eplerenone 1364 972 625 269 *Unadjusted HR, 0.78; 0.64, 0.95; p=0.01 Zannad et al N Engl Med 2011;364:11
As add-on ARB or Spironolakton? Spironolakton
Evidence based step by step medications Class II Class III Class IV ß blocker ACE inhibitor Spironolacton ß blocker ACE inhibitor ARB Spironolacton ß blocker ACE inhibitor ARB Spironolacton
Ivabradine
Update in Device treatment
CRT 1) EF < 35% 2) Bredd på QRS komplex > 120 ms och 3) Funktionklass III-IV 4) Optimal läkemedelsbehandling
ICD Sekundär Prevention 1. Hjärtsviktspatienter med överlevt hjärtstopp Primär Prevention 2. LVEF < 35% efter hjärtinfarkt (> 40 dagar efter hjärtinfarkt) samt icke-ischemisk hjärtsvikt 3. NYHA klass II-III 4. Optimal läkemedelsbehandling föreligger 5. Förväntad överlevnad med god livskvalitet > 1 år
PCI /CABG vid instabil koronarsjukdom med samtidig nedsättning av vänster kammares funktion.
Hjärtsvikt hos de äldre Var vi står? Vad vi gör?
CHF in the elderly - A Global Challenge
Desto högre risk Marparten >65 år 10% 8% 10 % 6% 4% 2% 0% 2 % 50 år 70 år Ju äldre,
Hjärtsvikt ett växande problem! 1) Medelåldern i befolkningen ökar 2) Antalet individer som överlever efter hjärtinfarkt ökar Till priset av utveckling av latent och symptomgivande hjärtsvikt! 3) Antalet hjärtsvikt patienter som överlever ökar
Sverige - Väldens äldsta befolkning 2006 1,5 milj >65 år Ca 500,000 >80 år Ca 70,000 >90 år 2020 2 milj >65 år Kostnad för sjukvård+ äldreomsorgen 150-160 miljader/år
Ett tillstånd med många ansikten
Höga ålder siffran Föråldrande process som bara fortsätter! Strukturellt & funktionellt
Och Mycket studier finns Hos de yngre Få studier finns Hos de äldre
Evidens baserad och rekommenderad svikt behandling Systolisk hjärtsvikt hos yngre
Hjärtsvikt hos äldre Behandlingar är ofta tyckande (empirisk) Systolisk Hjärtsvikt med bevarad systolisk funktion (HFNEF)
HFNEF Hjärtsvikt med bevarad EF Hjärtsvikt symptom LVEF > 50% och Normalstor VK Diastolisk dysfunktion HFNEF med DD (diastolisk dysfunktion)
Beta blockerare Hos äldre hjärtsvikt
Post hoc analys!
Death from cardiovascular causes % 20 <65 years % 20 65 years 15 10 5 Placebo p=0.024 Metoprolol CR/XL 15 10 5 Placebo p=0.0002 Metoprolol CR/XL 0 Risk reduction = 33% 0 3 6 9 12 15 18 Months of follow-up MERIT-HF 0 Risk reduction = 41% 0 3 6 9 12 15 18 Months of follow-up Deedwania P et al, Eur Heart J 2004;25:1300-9
Death from worsening heart failure % 6 5 4 3 2 1 0 <65 years Risk reduction = 8% 0 3 6 9 12 15 18 Months of follow-up MERIT-HF Metoprolol CR/XL Placebo ns % 6 5 4 3 2 1 0 65 years 0 3 6 9 12 15 18 Months of follow-up Placebo p=0.0005 Metoprolol CR/XL Risk reduction = 61% Deedwania P et al, Eur Heart J 2004;25:1300-9
Prospective study! The ONLY one!
Nebivolol in the elderly Flather et al., EHJ 2005
Effect of Beta blocker in the elderly?
RAAS Blockade in elderly population with CHF
Meta analys! For systolic CHF in the elderly
Prospective study! The ONLY one!
No benefit in long-term mortality and morbidity but effect after 1 year Cleland et al., Eur Heart J 2006
Effect of RAAS blockade in the elderly?
Effect of BB, ACEI, ARB Effect of aldosteron antagonist Effect of PCI/CABG Effect of CRT/ICD Usefulness of NTpro BNP?
Target dose Highest tolerable dose Which is better
Target dose Young = Highest tolerable dose Target dose Old = Highest tolerable dose
What shall we do?
CHF in the elderly