Hartversaking

1. Hartversaking Dr FCJ Bester

3. Obesity is a Major Risk Factor for Coronary Heart Disease (CHD)

4. Metabolic syndrome Slide 16: Metabolic syndrome The combination of insulin resistance, hypertension, diabetes and dyslipidemia commonly occur in the same individual obese patient and lead to significantly increased risk of major cardiovascular disease. Insulin resistance is thought to be the underlying factor for these conditions. Slide 16: Metabolic syndrome The combination of insulin resistance, hypertension, diabetes and dyslipidemia commonly occur in the same individual obese patient and lead to significantly increased risk of major cardiovascular disease. Insulin resistance is thought to be the underlying factor for these conditions.

5. Definisie Abnormaliteit van die kardiale funksie met gevolg dat die hart nie kan tred hou met die metaboliese behoeftes van die weefsel nie.

6. Tipes Hartversaking Diastolies (abnormale verslapping - stywe verdikte hartspier) Sistolies (Abnormale sametrekking)

7. Diastoliese hartversaking Isgemiese hartsiekte Amiloïedose Hemochromatose/siderose HOKM

8. Diastoliese hartversaking Isgemiese hartsiekte Amiloïedose Hemochromatose/siderose HOKM Hipertrofie as gevolg van hipertensie

9. Sistoliese hartversaking Isgemiese hartsiekte

10. Sistoliese hartversaking Isgemiese hartsiekte Virusmiokarditis Swangerskaps miopatie Idiopatiese kongestiewe miopatie

11. Sistoliese hartversaking Isgemiese hartsiekte Virusmiokarditis Swangerskaps miopatie Idiopatiese kongestiewe miopatie Voedingsgebreke Alkohol Diabetes (mikroangiopatie)

12. Biochemiese abnormaliteite/ veranderinge Energie metabolisme Regulatoriese proteïne Afname in Ca lewering aan selle Neurohumoraal Aktivering van RAAS ADH Atriale natriuretiese peptied

13. HVS Mimieke Tamponade, hipovolemie Glomerulonefritis Versnelde hipertensie Klep ruptuur

14. Oorsake van verergering Infeksie Anemie Tirotoksikose Disritme Tagi AV dissosiasie Bradikardi RK Endokarditis Pulmonale embolisme Stress (fisies/psigies) Verergerende hipertensie Miokard infarksie

15. Klinies - simptome Dispnee (NYHA I tot IV) Ortopnee PND Cheyne Stokes Uitputting/moegheid Abdominale simptome Serebraal - verwardheid/amnesie Nokturie

16. Klinies tekens NYHA I - min tot geen tekens PS: verplaas/hipertrofies Verhoogde JVD K3 (sistolies), K4 (diastolies) Ritmestoornisse, pulsus alternans Krepitasies Pleurale effusies/askites

17. Klinies tekens (vervolg) Kongestiewe hepatomegalie Geelsug Kardiale kageksie Prerenale versaking Proteïene in urine

18. Spesiale ondersoeke EKG: LBTB, tagikardi, oorladingspatroon

19. Spesiale ondersoeke EKG: LBTB, tagikardi, oorladingspatroon

20. Spesiale ondersoeke EKG: LBTB, tagikardi, oorladingspatroon

21. Spesiale ondersoeke

22. Spesiale ondersoeke EKG: LBTB, tagikardi, oorladingspatroon CXR: Stuwing, vergrote hartskaduwee.

23. Spesiale ondersoeke EKG: LBTB, tagikardi, oorladingspatroon CXR: Stuwing, vergrote hartskaduwee. Hartsonar: Goue standaard, ES afstand, LVUF.

24. Sonografie van hartversakingVensters

25. Parasternale Lang-as Verhouding tussen LA en Aorta L ventrikulêre wandbeweging Vind inkompetensies en stenoses Effusies

26. M-mode Meet van ventrikel in diastolie en sistolie Meet van septum en posterior wand

27. Parasternale kort asVlak: papillêre spier tot apeks Beoordeel wandbeweging en effusie

28. Parasternale kort asApikale 4/5 kamer aansig Kamergroottes, moontlike stolsels, effusies Doppler: A,M en T kleppe, IVOT/EF tye Kwantifiseer inkompetensies, ASD, VSD Kleurdoppler

29. Normale waardes Aortawortel: 1,8-3,7 cm Linker atruim: 1,9-4,0 cm Linker ventrikel: 3,5-5,7 cm LV uitwerpfraksie: 52-75% Linker ventrikel wande: Diastolies: 6-12 cm Sistolies: 10-15cm

30. Parasternale Lang-as Verhouding tussen LA en Aorta L ventrikulêre wandbeweging Vind inkompetensies en stenoses Effusies

31. Spesiale ondersoeke EKG: LBTB, tagikardi, oorladingspatroon CXR: Stuwing, vergrote hartskaduwee. Hartsonar: Goue standaard, ES afstand, LVUF. Isotoop studies: LVUF, wand diskinesie, Tallium perfusie studies, Tallium stress. Angiografie en termoverdunnings tegnieke. Magnetiese resonans beeldings.

32. Terapie Verwyder verergerende faktor Verwyder oorsaak Mediese terapie van probleem self Hartoorplanting Kunsharte

34. Mediese terapie AOE inhibeerders Begin met lae dosis Hoes en angioedeem

35. CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) Effek van Enalapril op erge kongestiewe HVS 253 pte, 127 enalapril en 126 placebo Enalapril 2,5 tot 20 mg/dag Verlaging van 40% mortaliteit na 6 maande. Studie prematuur gestaak!!

36. ATLAS Om die effek van Lisinopril op die mortaliteit van Kongestiewe HVS te evalueer. 3000 pte.

37. The reason for this broad mandate is that the efficacy of ACE inhibitors has been established in a number of large-scale trials across the entire spectrum of heart failure.The reason for this broad mandate is that the efficacy of ACE inhibitors has been established in a number of large-scale trials across the entire spectrum of heart failure.

38. Mediese terapie AOE inhibeerders Diuretika LUS - Titreer dosis Tiasiede Amiloried

39. Mediese terapie AOE inhibeerders Diuretika Digoksien Dosis: 0.125-0.25 mg/dag Newe effekte: Naarheid, delirium, ritmestoornisse, kleurvisie Doen vlakke by ingekorte nierfunksie

40. Digitalis investigation group trial Die effek van Digitalis op mortaliteit en morbiditeit 3397 digoksien en 3403 placebo Digoksien verminder nie die mortaliteit betekenisvol nie. (34,8% vs 35,1%) Verminder veregergering van simptome en hospitalisasies.

41. Mediese terapie AOE inhibeerders Diuretika Digoksien Aldosteroon antagoniste Spironolaktoon 25 tot 75 mg/d

42. RALES (Randomised Aldactone Evaluation study) Die voordeel van Spironolaktoon bygevoeg tot ACEI 200 pte op konvensionele terapie. Verdere evaluasie van 1400 pte. Dosis 25-75 mg/d 25% verlaging in mortaliteit Hiperkalemie by verhoogde dosisse.

43. Mediese terapie AOE inhibeerders Diuretika Digoksien Aldosteroon antagoniste ARB’s ELITE I en II studies: net so effektief as ACEI RAAS ondersoek die effek van byvoeging tot ACEI Gebruik by newe effekte van ACEI

44. PRAISE (Prosective randomised Amlodipine Survival evaluation) Effek van Amlodipien op die oorlewing van HVS 1153 pte (Amlodipien en placebo - dubbel blind) EF < 30 % Amlodipien 5-10mg/d Gebeurlikhede: Placebo 42%, Amlodipien 39% - nie statisties betekenisvol nie. Edeem en ortostatiese hipotensie in die Amlodipien groep.

45. Mediese terapie AOE inhibeerders Diuretika Digoksien Aldosteroon antagoniste ARB’s Beta blokkers

46. V-HeFT II studyRelationship between plasma norepinephrine and mortality

47. Evidence supporting the mandate for ? blockade in the treatment of chronic heart failure. Mortality results from the US Carvedilol Programme, the Second Cardiac Insufficiency Bisoprolol Study (CIBIS-II), and the Metoprolol CR/XL Randomised Intervention Trial in Heart Failure (MERIT-HF). Risk reductions for mortality were highly significant in all three trials: 65% in the US Carvedilol Programme and 34% in both CIBIS-II and MERIT-HF. Evidence supporting the mandate for ? blockade in the treatment of chronic heart failure. Mortality results from the US Carvedilol Programme, the Second Cardiac Insufficiency Bisoprolol Study (CIBIS-II), and the Metoprolol CR/XL Randomised Intervention Trial in Heart Failure (MERIT-HF). Risk reductions for mortality were highly significant in all three trials: 65% in the US Carvedilol Programme and 34% in both CIBIS-II and MERIT-HF.

49. COPERNICUS objectives and design. COPERNICUS objectives and design.

50. All patients in the COPERNICUS study had severe heart failure based on symptoms at rest or on minimal exertion for at least 2 months and a left ventricular ejection fraction below 25%. Patients had to be receiving treatment with diuretics and an ACE inhibitor. Patients with substantial fluid retention were not to be enrolled.All patients in the COPERNICUS study had severe heart failure based on symptoms at rest or on minimal exertion for at least 2 months and a left ventricular ejection fraction below 25%. Patients had to be receiving treatment with diuretics and an ACE inhibitor. Patients with substantial fluid retention were not to be enrolled.

51. Patients meeting eligibility criteria were randomised to receive placebo or carvedilol on a 1:1 basis. Patients received an initial dose of 3.125 mg carvedilol or placebo twice daily (bid). If tolerated, this was uptitrated at 2-week intervals to 6.25 mg, 12.5 mg and finally 25 mg twice daily. This is the same dosing regimen used in practice for mild and moderate heart failure. Patients then continued on the highest tolerated dose until the end of the trial.Patients meeting eligibility criteria were randomised to receive placebo or carvedilol on a 1:1 basis. Patients received an initial dose of 3.125 mg carvedilol or placebo twice daily (bid). If tolerated, this was uptitrated at 2-week intervals to 6.25 mg, 12.5 mg and finally 25 mg twice daily. This is the same dosing regimen used in practice for mild and moderate heart failure. Patients then continued on the highest tolerated dose until the end of the trial.

52. Kaplan-Meier curve displaying all-cause mortality in the placebo and carvedilol groups in the COPERNICUS trial. Highly significant risk reduction in patients treated with carvedilol(35% risk reduction). Separation of mortality curves seen after 3–4 months.Kaplan-Meier curve displaying all-cause mortality in the placebo and carvedilol groups in the COPERNICUS trial. Highly significant risk reduction in patients treated with carvedilol(35% risk reduction). Separation of mortality curves seen after 3–4 months.

53. Implications for public health The implications of the COPERNICUS results on public health are substantial.The implications of the COPERNICUS results on public health are substantial.

54. As can be seen, metoprolol and bisoprolol block only one of the deleterious pathways, propranolol two of them, whereas carvedilol blocks all three pathways leading from sympathetic activation to cardiotoxicity. Comprehensive adrenergic blockade provided by carvedilol is likely to provide greater protection of the heart against the deleterious consequences of sympathetic activation than selective, conventional, adrenergic blockade.As can be seen, metoprolol and bisoprolol block only one of the deleterious pathways, propranolol two of them, whereas carvedilol blocks all three pathways leading from sympathetic activation to cardiotoxicity. Comprehensive adrenergic blockade provided by carvedilol is likely to provide greater protection of the heart against the deleterious consequences of sympathetic activation than selective, conventional, adrenergic blockade.

55. Recommended starting and target doses according to the Medical Letter, an important independent clinical publication in the USA. The target doses described for carvedilol include a wide range of doses (based on the results of the MOCHA study), whereas only a high single target dose is recommended for both metoprolol and bisoprolol, since data supporting the use of low doses of metoprolol and bisoprolol are lacking. Recommended starting and target doses according to the Medical Letter, an important independent clinical publication in the USA. The target doses described for carvedilol include a wide range of doses (based on the results of the MOCHA study), whereas only a high single target dose is recommended for both metoprolol and bisoprolol, since data supporting the use of low doses of metoprolol and bisoprolol are lacking.

58. Protective effect of decreased b-adrenergic signal transduction in myocardial failure or hypertrophy Increased cardiac adrenergic drive

61. Benefits of balanced ? and ? blockade

62. Carvedilol improves renal blood flow in heart failure patients

63. Change in urinary albumin level with carvedilol or atenolol

64. Evidence Based Medicine: Duiretika ACEI of ARB’s Spironolaktoon Digoksien Betablokkers in lae dosis. Toekoms: ANP reseptor moduleerders Endotelien antagoniste