1 / 57

Congestive Heart Failure

Congestive Heart Failure. Dr Bernard Silke, MD, DSc, FRCP, Cardiovascular Physician, St. James’ Hospital, Dublin 8. Congestive Heart Failure Changing population trends. Clinical Scenario. JB is 75 and is a retired publican. First presented 12 yr ago with MI.

deacon-wong
Download Presentation

Congestive Heart Failure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Congestive Heart Failure Dr Bernard Silke, MD, DSc, FRCP, Cardiovascular Physician, St. James’ Hospital, Dublin 8.

  2. Congestive Heart FailureChanging population trends

  3. Clinical Scenario JB is 75 and is a retired publican. First presented 12 yr ago with MI. • A strong family Hx of CVS disease. Father died at age 40 with Stroke. Mother had angina. • Subsequent LVF 5 yr ago with hospitalization. Echo dilated / asymmetrical contraction / dysynergy. • Ejection Fraction 35%. Effort Dyspnoea • What are the therapeutic options?

  4. Congestive Heart FailureIncidence and age Eur Heart J 1999: 20; 421-428.

  5. Congestive Heart FailureChanging population trends • < 5% of population • CHF in 1.5% (25-75 yr) • LV Systolic function abnormality in 1% • Clinical CHF - 1% • Suspect CHF - 1%

  6. Congestive Heart FailureChanging population trends • MI deaths peaked 1985 Rate 215 / 100,000 • Between 1985 - 1995 mortality rates decrease by 33% (215.3 - 144.2) • Numbers of very elderly predicted to increase by 30% and 57% over next two decades

  7. Heart FailureDefinition • Heart unable to meet peripheral blood flow requirements without a rise in filling volume • Contraction energy is reduced • Stroke volume incompletely expelled • Chamber volume increases

  8. Heart FailureNatural history 0 100 Rest symptoms Pump Failure No symptoms No deaths Morbidity Mortality 100 0 Time from onset

  9. Heart FailureTherapeutic goals Normal A I Stroke Volume A + V V CHF D Ventricular Filling Pressure

  10. Heart FailureEjection Fraction • Ejection Fraction - % of EDV ejected each beat • Normal 50 - 75% • Impaired function < 40% • Symptomatic < 30% • If EDV 100 ml • Stroke volume 65 ml • CHF < 40 ml

  11. Heart FailureTherapeutic implications • Volume overload • Diuretics • Elevated impedance • Vasodilators • Decreased contractility • Inotropes

  12. Heart FailureClinical goals • Patient oedema free • Ambulant • Avoid hospitalisation • Optimise quality of life

  13. Heart FailureClinical assessment • Peripheral oedema – none to minimal • Paroxysmal nocturnal dyspnoea - infrequent • Posture at night - < 2 pillows • Dyspnoea – absent at rest, activity possible • Nocturia – common and not significant

  14. Heart FailureTherapeutic groups • Diuretics Thiazide group, Loopdiuretics • Angiotensin converting enzyme inhibitors • Long-acting nitrates • Captopril, Enalapril, Lisinopril, Trandolopril • Inotropes • Digoxin

  15. DIURETICS Thiazides Inhibit active exchange of Cl-Na in the cortical diluting segment of the ascending loop of Henle Cortex K-sparing Inhibit reabsorption of Na in the distal convoluted and collecting tubule Loop diuretics Inhibit exchange of Cl-Na-K in the thick segment of the ascending loop of Henle Medulla Loop of Henle Collecting tubule

  16. Heart Failure Diuretics : Sites of Action Distal CT (Thiazides) Na/Cl Glomerulus Amiloride Na Proximal Tubule (CAI) Ascending Limb (Loop) Spironolactone Na/K Na/K/Cl Collecting Duct

  17. Heart Failure Diuretics : Sites of Action Tubular cell hypertrophy Ascending Limb (Loop) Sodium load to distal nephron increased Na/K/Cl Collecting Duct

  18. Heart Failure Diuretics : Resistance • Check compliance • Check Na+ intake • Low salt diet • Avoid bread / processed foods • Daily fluid allowance 1L • Check not taking a NSAID • Increased dose of a loop diuretic? • Metolazone (pulse 2.5 mg) once / twice week

  19. Heart FailureACE Inhibitors • Prolong survival in early and established CHF • Improve Quality of Life • Relieve symptomatic congestion • Increase exercise tolerance • Reduce hospitalisation

  20. Heart Failure Choice of ACE Inhibitor • Captopril - first generation • Short duration of action • Multiple dose administration (50 mg tds) • Enalapril, Lisinopril - second generation • Longer duration of action (once daily) • Increased liklihood of hypotension • Perindopril, Trandolopril - third generation • Vascular selective • Favourable side-effect profile • Lack of first-dose effect

  21. Heart Failure Benefits of ACEI 0.8 0.7 Placebo 0.6 PROBABILITYOFDEATH p< 0.001 0.5 0.4 p< 0.002 0.3 Enalapril 0.2 0.1 0 CONSENSUS N Engl J Med 1987;316:1429 0 1 2 3 4 5 6 7 8 9 10 11 12 MONTHS

  22. 50 40 30 20 10 0 Heart Failure Benefits of ACEI p = 0.0036 Placebo n=1284 % MORTALITY Enalapril n=1285 n = 2589 CHF - NYHA II-III - EF < 35 48 0 6 12 18 24 30 36 42 SOLVD (Treatment)N Engl J M 1991;325:293 Months

  23. Heart Failure Contemporary management with ACEI • Considerable variations in ACE prescribing • ACE Inhibitors used in 30 - 60% of CHF cases • Elderly less likely to be treated (21 vs 69%) • Physician perceptions of contra-indication • No documented contra-indications in 35% • Elderly high rate of morbid events • Withhold ACE more complications (p < 0.01) Am. Heart J. 1998:136;43.

  24. Enalapril Captopril Ramipril Lisinopril Trandolapril Quinapril 20 150 10 10 / 20 4 40 Heart Failure Survival benefits & dosage (mg / day) Am. Heart J. 1998:136;43.

  25. Heart Failure Contemporary issues & ACEI • Pharmacodynamic response to ACEI elderly • Valid concerns hypotension / renal dysfunction • Reluctance to adequately dose titrate • Many patients left on initiation dosage • Elderly patients will tolerate ACEI and achieve target doses if titrated gradually • Suboptimal Rx important due to high morbidity Am. Heart J. 1998:136;43.

  26. 2% 4% 3% 9% • 82% Heart Failure Contemporary management with ACEI • SPICE registry • Eight countries • Hospital cases • Consecutive 9581 • Current practice • USA and Europe

  27. Heart FailureACEI ADR profile • SPICE registry of 8485 cases • Cough (308 - 4%) • Renal sufficiency (188 - 2%) • Symptomatic hypotension (147 - 2%) • Hyperkalaemia (35) • Rash / pruritus (25) • Angioedema / analyphaxis (19)

  28. DIGOXIN Na-K ATPase Na-Ca Exchange Na+ K+ Na+ Ca++ Ca++ Myofilaments K+ Na+ CONTRACTILITY

  29. Heart Failure Drug Therapy : Digoxin • Positive Inotropic • S-A and A-V Nodal actions • Enhanced Automaticity

  30. DIGOXIN EFFECT ON CHF PROGRESSION 30 Placebo n=93 DIGOXIN Withdrawal % WORSENING OF CHF 20 p = 0.001 DIGOXIN: 0.125 - 0.5 mg /d (0.7 - 2.0 ng/ml) EF < 35% Class I-III (digoxin+diuretic+ACEI) Also significantly decreased exercise time and LVEF. 10 DIGOXIN n=85 0 60 0 20 40 80 100 RADIANCE N Engl J Med 1993;329:1 Days

  31. Heart Failure The DIG Study • CHF patients (6800) studied 1991 - 1995 • Sinus rhythm; E.F. < 45% • NYHA Class III 33%; Class II < 50% • Background ACEI and/or diuretic (78%) • Digoxin (median 250 ug / day) vs. placebo • Endpoints: mortality and hospitalisation N. Engl. J. Med. 1997: 336; 525

  32. 50 40 30 20 10 0 OVERALL MORTALITY Placebo n=3403 % p = 0.8 DIGOXIN n=3397 0 12 24 36 48 DIG Study N. Engl. J. Med. 1997: 336; 525 Months

  33. Heart Failure The DIG Study • Mortality similar (34.8% vs. 35.1%) • Hospitalisations reduced 22% (16 - 28) • Benefits greatest in those at highest risk • Lower E.F. ( < 25% ) • Enlarged hearts • NYHA Class III & IV • Digoxin toxicity • Ventricular fibrillation / tachycardia • Supraventricular dysrhythmia • Second or 3rd degree heart block N. Engl. J. Med. 1997: 336; 525

  34. Heart Failure The DIG Study • No substantial change in mortality /morbidity • No ethical mandate for its use • May be prescribed for symptomatic relief • Other drug categories have proven benefit • ACEI and ß-blockers drugs N. Engl. J. Med. 1997: 336; 575

  35. Heart Failure Digoxin Therapeutics • Atrial fibrillation with uncontrolled response • Reduce apex rate to 100 or less. • Loading 15 ug / kg in three doses over 24 hr • Maintenance dose 250 to 500 ug / day • Therapeutic concentration 0.8 - 2.0 ng / ml

  36. Heart Failure ß - blocking Therapy • Reduce heart rate & myocardial contractility • Concern about risk of cardiac depression • In CHF ß - adrenoceptors are downregulated • Cardiac efficiency impaired by compensation • Upregulation during ß - blocking treatment • CIBIS I in 641 CHF - 20% mortality reduction

  37. US Carvedilol Programme Survival 1.0 0.9 0.8 0.7 0.6 0.5 Carvedilol (n=696) b blockers in heart failure – all-cause mortality Placebo (n=398) Risk reduction=65% p<0.001 0 50 100 150 200 250 300 350 400 Days Packer et al (1996) Survival Mortality (%) CIBIS-II MERIT-HF 1.00.80.6 0 20 Placebo Bisoprolol 15 Metoprolol CR/XL 10 Placebo Risk reduction=34% Risk reduction=34% 5 p=0.0062 p<0.0001 0 0 200 400 600 800 0 3 6 9 12 15 18 21 Time after inclusion (days) Months of follow-up The MERIT-HF Study Group (1999) CIBIS-II Investigators (1999)

  38. Heart Failure ß - blocking Therapy • Over 13 000 patients evaluated in placebo-controlled clinical trials • Consistent improvement in cardiac function, symptoms and clinical status • Decrease in all-cause mortality by 30–35% (p<0.0001) • Decrease in combined risk of death and hospitalisation by 25–30% (p<0.0001)

  39. Background • Angiotensin II type 1 (AT1) receptor blockers (ARBs) provide a pharmacologically distinct mechanism of inhibiting the renin-angiotensin-aldosterone system • ARBs offer the potential to produce further clinical improvements above and beyond ACE inhibitors as well as an alternative for those previously intolerant to an ACE inhibitor

  40. CHARM Programme 3 component trials comparing candesartan to placebo in patients with symptomatic heart failure CHARMAlternative CHARM Added CHARMPreserved n=2028 LVEF £40%ACE inhibitor intolerant n=2548 LVEF £40%ACE inhibitor treated n=3025 LVEF >40%ACE inhibitor treated/not treated Primary outcome for each trial: CV death or CHF hospitalisation Primary outcome for Overall Programme: All-cause death

  41. Every 4 months until study end31 March 2003 Time 0 w 2 w 4 w 6 w 6 m Visit 1 2 3 4 5 Study designDose-titration and visit schedule Candesartan/matching placebo once daily 32 mg 16 mg 8 mg 32 mg 4 mg 16 mg 8 mg

  42. Baseline characteristics Alternative Added PreservedOverall n=2028 n=2548 n=3023 n=7599 Mean age (years) 67 64 67 66 Women (%) 32 21 40 32 NYHA class (%) II 48 24 60 45 III 49 73 38 52 IV 3 3 2 3Mean LVEF 30 28 54 39 Medical history (%) myocardial infarction 61 56 44 53 diabetes 27 30 28 28 hypertension 50 48 64 55 atrial fibrillation 25 26 29 27

  43. CHARM Programme 3 component trials comparing candesartan to placebo CHARMAlternative CHARM Added CHARMPreserved n=2028 LVEF £40%ACE inhibitor intolerant n=2548 LVEF £40%ACE inhibitor treated n=3025 LVEF >40% ACE inhibitor treated/not treated Primary outcome: CV death or CHF hosp

  44. 50 406 (40.0%) Placebo 40 334 (33.0%) 30 Candesartan 20 10 HR 0.77 (95% CI 0.67-0.89), p=0.0004Adjusted HR 0.70, p<0.0001 0 0 1 2 3 3.5 years CHARM-Alternative: Primary outcome CV death or CHF hospitalisation % Number at risk Candesartan 1013 929 831 434 122 Placebo 1015 887 798 427 126

  45. CHARM-Alternative Investigator reported CHF hospitalisations Placebo Candesartan Proportion of patients (%) Number of episodes p=0.0001 p<0.0001 Hospitalisations Patients hospitalised

  46. CHARM-Alternative Permanent study drug discontinuations Percent of patients Placebo 25 Candesartan 21.5 19.3 20 15 10 6.1 5 3.7 2.7 1.9 0.9 0.4 0.2 0.3 0.1 0 0 AE/lab. abnorm. Hypo-tension Increased creatinine Increasedpotassium Cough Angio-edema p=0.23 p<0.0001 p<0.0001 p=0.0005 p=0.69 p=0.50

  47. CHARM-AlternativeConclusions • Despite prior intolerance to another inhibitor of the renin-angiotensin-aldosterone system, candesartan was well tolerated • In patients with symptomatic chronic heart failure and ACE-inhibitor intolerance, candesartan reduces cardiovascular mortality and morbidity

  48. Cardioprotective Effects of Valsartan as Seen in the Valsartan-Heart Failure Trial (Val-HeFT) Jay N. Cohn, MD Professor of Medicine University of Minnesota Medical School Minneapolis, Minnesota, USA

  49. Study Overview 5010 patients18 years; EF <40%; NYHA II-IV; LVIDd >2.9 cm/m2 Receiving background therapy ACE inhibitors (92.7%), diuretics (85.8%),digoxin (67.3%), -blockers (35.6%) Randomized to Valsartan40 mg bid titrated to160 mg bid Placebo Cohn JN et al. Eur J Heart Fail. 2000;2:439-446.

  50. Patients’ Baseline Characteristics Valsartan(n = 2511) Placebo (n = 2499) Mean age (y) 62.4 63.0 Gender, male (%) 79.9 80.0 Race (%) White 89.8 90.9 NYHA Class (%) II 62.1 61.4III 36.1 36.3IV 1.7 2.2 Ejection fraction (%) 26.6 26.9 Background therapy (%)Diuretic 85.8 85.2 Digoxin 67.1 67.6 -Blocker 34.5 35.3 ACE inhibitor 92.6 92.8 Cohn JN et al. N Engl J Med. 2001;345:1667-1675.

More Related