A patient with decompensated HF Professor Michel KOMAJDA University Pierre & Marie Curie Pitie Salpetriere Hospital Department of Cardiology Paris (France)
Declaration Of Interest 2010 Speaker : Servier, Menarini, Sanofi, Boehringer Ingelheim, Astra Zeneca, Glaxo Smithkline Consultant / Trial Committee member : Servier, Johnson & Johnson, Nile Therapeutics, Sanofi, Bristol Myers-Squibb
Case description Mr D. 69 years is referred to the emergency unit of your hospital for severe dyspnoea. Symptoms worsened progressively the week before admission. Hx: Dilated cardiomyopathy discovered 6 years ago. Most recent evaluation 1 year ago: NYHA II.. ECG : sinus rhythm 85 bpm. QRS duration:90msec Echo doppler: diffuse hypokinesia.lvef=23%. LVEDD = 69mm. Treatment: furosemide 40mg od/ Ramipril 5mg od/ carvedilol l 12.5 mg bid.
Recent Hx: Clinical Case Since he felt tired, he stopped all his medications four days ago and had several diners in gastronomic restaurants (French cuisine!!) Physical examination: Weight: 76kgs (+4) Height: 168 cms HR = 85 bpm Rhythm regular. BP: 105/70 mm Hg Bilateral diffuse pulmonary crackles. S3 gallop. Bilateral l foot and ankle edema.
Clinical Case ECG: sinus rhythm 100 bpm QRS = 90msec X ray: CTR = 0.60. Diffuse bilateral pulmonary edema Biology : Na + = 138meq/l. K + = 3.9 meq/l. S creatinine = 139 μm/l. Sa O 2 = 91%
Clinical Case What are the therapeutic options?
A. Salt restriction B. IV Loop Diuretics C. Resume previous treatments D. Add new medications E. Consider other procedures
What do ESC guidelines say?
Symptomatic heart failure + reduced ejection fraction Detect major Co-morbidities and Precipitating Factors Non-cardiovascular Anemia Pulmonary disease Renal dysfunction Thyroid dysfunction Diabetes Cardiovascular Ischemia/CAD Hypertension Valvular dysfunction Diastolic dysfunction Atrial fibrillation Ventricular dysrhythmia Bradycardia Yes Diuretic + ACE inhibitor (or ARB) Titrate t to clinical i l stability Betablocker Persisting signs and symptoms? ADD aldosterone antagonist t OR ARB No Yes Persisting symptoms? No QRS duration > 120 msec? LV ejection fraction < 35%? Yes No Yes No Consider: CRT or CRT-D Consider: digoxin, hydralazine/nitrate LVAD, transplantation Consider ICD No further treatment
ESC guidelines 2008 Weight monitoring : In case of sudden unenexpectedweight gain > 2 kgs in 3 days, patients may adjust their diuretic dose and should alert the health care team. Class I Level of evidence C Sodium intake: Sodium restriction is recommended in symptomatic HF and excessive intake of Na + should be avoided Class IIa Level of evidence C
Diuretics: ESC Guidelines 2008 Are recommended in HF patients with signs or symptoms of congestion. Class I, Level B In general, loop diuretics are required in moderate to severe HF. If the effect is not achievable despite rapid uptitration, continuous furosemide infusion can be considered.
ESC Guidelines 2008 ACE Inhibitors: Unless contra indicated or not tolerated, ACE-I should be used in all patients with symptomatic HF and LVEF<40 %. Class I, Level A
ACE-inhibitor trials in heart failure / LV- dysfunction - mortality Randomized large (>1000 patients), long-term (1 year) trials ACE-inhibitor vs placebo 12 763 patients in 4 trials SAVE, AIRE, TRACE SOLVD 0.74 0.87 Total 0.80 0.5 Better 0.75 1.0 ACE-inhibitor Worse Flather et al Lancet 2000
Beta Blockers: ESC Guidelines 2008 Unless contra indicated or not tolerated, abb should be used in all patients with symptomatic HF and LVEF< 40 %. Class I Level A. Patients should be clinically stable. Cautious initiation is possible in a recently decompensated patient provided that patient has improved with other treatments, is not dependent on an IV inotrope and can be observed in hospital >24 hours after initiation.
Survival 1.0 0.9 0.8 US Carvedilol Programme Carvedilol n=696 Placebo n=398 Survival 100 90 80 COPERNICUS Carvedilol 0.7 0.6 0.5 Risk reduction=65% p<0.001 0 50 100 150 200 250 300 350 400 Packer et al (1996) Days 70 Placebo Risk reduction=35% 60 0 0 p=0.00013 3 6 9 12 15 18 21 Packer et al (2001) Months Survival 1.0 0.8 0.6 0 CIBIS-II Risk reduction=34% p<0.0001 Bisoprolol Placebo Time after inclusion (days) 0 200 400 600 800 Mortality (%) 20 15 10 5 0 MERIT-HF CIBIS-II II Investigators (1999) The MERIT-HF Study Group (1999) p=0.0062 Months of follow-up 0 3 6 9 12 15 18 21 Placebo Metoprolol CR Risk reduction=34%
Angiotensin Receptor Blockers (ARBs) (1) Patients who should get an ARB LVEF 40% and either: As an alternative in patients with mild to severe symptoms (NYHA functional class II IV) who are intolerant of an ACEI. (I level B) Or in patients with persistent symptoms (NYHA functional class II IV) despite treatment with an ACE-I and beta-blocker.(i blocker.(i level A) /
CHARM-Added: Added: Primary outcome CV death or CHF hospitalisation (% of patients) 50 538 (42.3%) Placebo 40 483 (37.9%) 30 Candesartan 20 10 HR 0.85 (95% CI 0.75-0.96), p=0.011 Adjusted HR 0.85, p=0.010 0 Number at risk: 0 1 2 3 3.5 years Candesartan 1276 1176 1063 948 457 Placebo 1272 1136 1013 906 422
ESC guidelines on CHF 2005 Aldosterone receptor antagonist: Is recommended in addition to ACE-inhibition and beta-blockade blockade in heart failure after myocardial infarction with left ventricular systolic dysfunction and signs of heart failure to reduce mortality and morbidity (level of evidence B, class I).
Effect of Eplerenone in Post-MI LVD & HF: EPHESUS Total Mortality CV Mortality/CV Hospitalization Cumulativ ve Incidence e (%) 20 10 0 0 6 RR=0.85 (95% CI, 0.75-0.96) P=0.008 12 18 24 30 36 Cumulativ ve Incidence e (%) 40 30 20 10 0 0 6 RR=0.87 (95% CI, 0.79-0.95) P=0.002 12 18 24 30 36 Months Since Randomization Months Since Randomization Placebo (N=3313) Eplerenone (N=3319) Pitt B, et al. N Engl J Med. 2003;348:1309-1321
Inclusion Criteria Inclusion > 55 years of age NYHA functional class II Ejection fraction < 30% (or, if between 31% and 35%, QRS >130 msec) Treated with the recommended or maximally tolerated dose of ACE inhibitor (or an ARB or both) and a beta-blocker (unless contraindicated). Within 6 months of hospitalization for a cardiovascular reason [or, if no such hospitalization, BNP > 250 pg/ml or NT-pro-BNP >500 pg/ml (males) or 750 pg/ml (females) ] Exclusion Serum potassium > 5.0 mmol/l egfr < 30 ml/min/1.73 m 2 Need for a potassium-sparing p diuretic Any other significant comorbid condition
Study Design and Sample Size 25 mg Eplerenone 50 mg qd Screen 25 mg 1 3 Months Month Randomization Placebo 50 mg qd Follow-up Primary endpoint: CV death or hospitalization for HF
Primary Endpoint Cardiovascular Death or Hospitalization for HF 50 40 HR [95% CI] = 063[0 0.63 [0.54, 0.74] P < 0.0001 0001 Placebo 356 (25.9%) Prima ary Endpoint Cumulative K-M rat te 30 20 10 Eplerenone 249 (18.3%) 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
Mortality From Any Cause 40 30 HR [95% CI] 0.76 = [0.62, 0.93] P = 0.0081 Placebo 213 (15.5) No.at risk 20 -M Rate (%) 10 -Cause Mortality: All Cumulative K 0 0 1 2 3 Years from Randomization Placebo 1373 947 587 242 Eplerenone 1364 972 625 269 Eplerenone 171 (12.5) *Unadjusted HR, 0.78; 0.64, 0.95; p=0.01
Heart Failure Hospitalization ization: e (%) ure Hospitali ative K M Rat Heart Fail Cumula 40 30 20 10 HR [95% CI] = 058[0 0.58 [0.47, 070]P<00001 0.70] 0.0001 Placebo 253 (18.4%) Eplerenone 164 (12.0%) 0 0 1 2 3 No. at Risk Years from Randomization Placebo 1373 848 512 199 Eplerenone 1364 925 562 232 *Unadjusted HR, 0.61; 0.50, 0.75; p <0.0001
ACE-I Aldosterone Antagonists ARBs Contra-indications K + > 5 meq/l + + + Creatinine > 220 µ M/l + + + Reduce 50% K + > 5.5 Creatinine i > 265 µ M/l Creatinine > 220 µ M/l Stop K + > 6 Creatinine > 310 µ M/l + + + + + As ACE-I + + As ACE-I +
Study design Screening 7 to 30 days Ivabradine 5 mg bid Matching gp placebo, bid Ivabradine 7.5/5/2.5 mg bid according to HR and tolerability D0 D14 D28 M4 Every 4 months 3.5 years Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81.
Inclusion criteria 18 years Class II to IV NYHA heart failure Ischaemic/non-ischaemic aetiology LV systolic dysfunction (EF 35%) Heart rate 70 bpm Sinus rhythm Documented hospital admission for worsening heart failure 12 months Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81.
Primary composite endpoint Cumulative frequency (%) 40 30 Ivabradine n=793 (14.5%PY) Placebo n=937 (17.7%PY) Ivabradine Placebo HR = 0.82 [95% CI 0.75-0.90] p<0.0001-18% 20 10 0 0 6 12 18 24 30 Months
Hospitalization for heart failure Cumulative frequency (%) 30 Ivabradine Placebo Ivabradine n=514 (9.4%PY) Placebo n=672 (12.7% PY) HR = 0.74 [95% CI 0.66-0.83] p < 0.0001 20-26% 10 0 0 6 12 18 24 30 Months
ESC Guidelines 2008 ICD therapy in primary prevention is recommended to reduce mortality in patients with left ventricular dysfunction after a prior myocardial infarction at least 40 days post MI (class I level A) / non ischaemic cardiomyopathy (class I level B) and with LVEF < 35 %, in NYHA class II/III, under optimal therapy, and with a reasonable expectation of survival and good functional status for >1 year.
SCD-HeFT 2521 pts with CHF class II-III III and LVEF<35% Randomized to placebo, amiodarone or single-lead, lead, shock-only only ICD Bardy et al NEJM, 2005
لكم شكرا شكا جزيال زال