Heart failure - pathogenesis and current management

Heart failure pathogenesis with 2013 AHA guidelines on management with ESC 2013 updates. Acute and chronic heart failure with new drugs.

1. Heart Failure - Pathogenesis and Current Management Dr Subhasish Deb Dept. of General Medicine Burdwan Medical College

2. Definition “Heart (or cardiac) failure is the patho -physiological state in which the heart is unable to pump blood at a rate to commensurate with the requirements of the metabolizing tissues or can do so only from an elevated filling pressure” - Eugine Braunwald

3. Disease Burden Reliable estimates of heart failure are lacking in India because of the absence of a surveillance program to track incidence and prevalence Prevalence in developed countries = 2% Among people over 65yr = 6-10%

4. Etiology 1.

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7. CO = HR * stroke volume Intrinsic health of myocardium Preload Afterload

8. AFTERLOAD EDV EDV PRELOAD INTRINSIC ACTIVITY

9. Pathogenesis Described in the context of 3 phases: The Index event Compensatory mechanism activation Advantages Disadvantages LV Remodeling

10. INDEX EVENT Anything that causes a loss of functioning cardiac myocytes My be abrupt in onset (MI) or insidious (chronic volume or pressure overload states) It ultimately causes a decline in pumping capacity of the heart

11. Compensatory mechanism These are activated in the presence of cardiac injury, allowing patients to sustain and modulate LV function for a period of months to years

12. I. Activation of sympathetic system: CCF decreased BP in carotid sinus stimulation of CNS inc. sympatheic outflow Advantages: Stimulates SA node – inc HR Symp outflow acts as inotrope – inc CO Adrenals stimulated – release of adrenaline – inc HR & CO Venoconstriction – inc EDV – inc stroke volume

13. II. Activation of RAAS Stimulus : decreased renal perfusion due to 1. dec CO 2. inc vasoconstriction due to sympathetic activity

14. Advantages: Angio II is a venoconsrtictor – inc EDV Simulates symp nerve endings Acts on ZG of adrenals – aldosterone – retension of salt and water ( intinaly good)

15. 3. ADH/vasopressin release: Retention of water Veno and arteriolo constriction 4. ANP & BNP release: Beneficial as they counter the dangerous effects of other compensation mechanisms. When more salt retained – natriuresis When more water retained – diuresis If vasoconsriction is too much – vasodilatation

16. Disadvantages of neurohumoral activities If we allow the compensatory mechanisms to go chronic, don’t correct the underlying cause and do not correct these comp. mechanisms pharmacologically, they bring about disadvantages. Chronic salt and water retension = chronic preload Chronic arterioloconstriction = chronic afterload These chronic preload and afterload cause rmodeling of the heart

17. Remodeling Chronic stress causes altered genomic expression of myocardium which starts producing altered proteins which are not good functionally Ex of altered protein : CaATPase Calcium handling is abnormal

18. Pathophysiology in relation to ventricular function curve CO EDV 5 140 In L/min In ml 2 3 200 250 LVEF =50% HR=72/min A B C D A= normal B= uncompensated C= compensated D= decompensated

19. Effect of drugs on ventricular function curve CO EDV 5 140 In L/min In ml 2 3 200 250 LVEF =50% HR=72/min A B C D diuretic inotrope Does not ascend in the same path when drugs given

20. Laplace’s Law Pressure = Tension/Radius Diuretic/ ACEi /ARB : radius decreases so pressure generated inc. Inotrope : increases the tension so pressure in creases.

21. Pathophysiology in a nutshell Index event/ increased work load on heart Activation of compensatory mechanisms Compensated HF Self-defeating effects of compensatory mechanisms Decompensated HF

22. Stages of heart Failure NYHA classification: Asymptomatic Symptoms at moderate physical activity Symptoms on mild activity Symptoms at rest

23. ACC/AHA stages of Heart Failure A Risk Factors Risk Factors + Structural/ Functional changes Risk Factors + Structural/ Functional Changes + Has clinical Features / on trearment Very frequently Hospitalized And cannot be Discharged Safely or Cannot wean off From IV ionotropes or On mechanical assist device or Waiting for heart transplant B C D SYMPTOMATIC HTN DM h/o Cardiotoxic drug Rhumatic fever f/o cardiomyopathy Wall Hypertrophy Fibrosis Dilatation RWMA Valve lesion Post MI (scarred heart) Refractory

24. AHA stages vs NYHA No criteria to treat pts early (stage A) NYHA is subjective so cannot be uniform (pts tell you the symptom) Cannot develop a proper prognosis (pt on NYHA III can go to II after treatment. But once in Stage C can never go back to Stage B. No jumping of stages )

25. This classification system is intended to complement but not to replace the New York Heart Association ( NYHA) functional classification , which primarily gauges the severity of symptoms in patients who are in stage C or D.

26. Management of Heart failure 1. Initial and serial evaluation of the HF pt 2. Treatment through stages A to D 3. Acute Heart Failure

27. Initial and serial evaluation of the HF patient History and Physical Examination Diagnostic tests Biomarkers in ambulatory/outpatients Biomarkers in hospitalized pts Non invasive cardiac imaging Invasive cardiac imaging

28. History and physical examination Thorough history and physical exam should be obtained/performed to identify cardiac and non cardiac disorders A 3 generation family hist. in pts with idiopathic DCM Assessment of volume status and vital signs Weight Peripheral edema JVP estimate Orthopnea

29. Diagnostic tests Initial labs: CBC Urine r/e Electrolytes (including Ca & Mg) BUN, Cr FBS, PPBS LFT Fasting lipid TSH Serial monitoring with electrolytes and RFT

30. Biomarkers in ambulatory/outpatients BNP and NT- proBNP for supporting clinical decision making regarding diagnosis BNP and NT- proBNP for prognosis

31. Biomarkers in Acute/Hospitalized BNP and NT- proBNP for supporting clinical decision making regarding diagnosis BNP and NT- proBNP for prognosis

32. Non invasive cardiac imaging CXR to assess cardiac size, pulmonary congestion and to detect other cardiac or non cardiac disease 2D echo with doppler to asses: EF Wall thickness Wall motion Valve function Repeat measurement of EF in: HF pts with significant change in clinical status Who have recovered from a clinical event Who may be candidates for device therapy

33. Invasive cardiac imaging Invasive hemodynamic monitoring with pulmonary artery catheter should be performed to guide therapy in patients who have reparatory distress or clinical evidence of impaired perfusion in whom adequacy or excess of intracardiac filling pressure cannot be determined from clinical assessment

34. Management of Heart failure 1. Initial and serial evaluation of the HF pt 2. Treatment through stages A to D 3. Acute Heart Failure

35. STAGE A Htn and lipids should be managed as per contemporary guidelines Other risk factors such as DM, tobacco smoking, obesity, cardiotoxic agents should be controlled or avoided

36. STAGE B Pts with recent or remote h/o of MI or ACS and reduced Ef , ACEi should be used to prevent symptomatic HF and reduced mortality For all pts. with a recent or old h/o of MI or ACS and reduced EF, evidence based beta blockers should be used to reduce mortality For all pts. with a recent or old h/o of MI or ACS statins should be used to reduce symptomatic HF and cardiovascular events

37. In patients with structural cardiac abnormalities, including LV hypertrophy, in the absence of a history of MI or ACS, blood pressure should be controlled in accordance with clinical practice guidelines for hypertension to prevent symptomatic HF ACE inhibitors should be used in all patients with a reduced EF to prevent symptomatic HF, even if they do not have a history of MI Beta blockers should be used in all patients with a reduced EF to prevent symptomatic HF, even if they do not have a history of MI

38. STAGE C – Non pharmacological t/t

39. Device therapy in HFrEF ICD for primary prevention of SCD in HFrEF , 40 days post MI NYHA class II or III LVEF <= 35% On chronic GDMT and expected to live >1 yr ICD for primary prevention of SCD in HFrEF , 40 days post MI NYHA class I LVEF <=30% On chronic GDMT and expected to live >1 yr

40. Sudden Cardiac Death Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 hour of symptom onset) in a person with known or unknown cardiac disease.

41. Implantable Cardiac Defibrillator ICD keeps track of each beat If heart goes into a fast rhythm w hich is potentially life t hreatening -- SHOCK

42. Cardiac Resynchronization therapy BACKGROUND: Approx 25% pts with CHF have intraventricular conduction delay; commonly LBBB Electrical activation of lateral aspect of LV can be delayed in relation to that of RV and/or IV septum This results in: Dyssynchronous electrical activation and contraction Unequal distribution of myocardial work load Altered myocardial blood flow and metabolism

43. Lateral view X-ray of 1 st successful cardiac resynchronization therapy University hospital of Rennes, 1994

44. Simultaneous pacing of RV & LV = BIVENTRICULAR PACING Leads in RA, RV & LV LV paced via coronary sinus

45. Stage D A subset of patients with chronic HF will continue to progress and develop persistently severe symptoms despite maximum GDMT. Various terminologies have been used to describe this group of patients who are classified with ACCF/AHA stage D HF, including “ advanced HF ,” “ end-stage HF ,” and “ refractory HF .”

46. In the 2009 ACCF/AHA HF guideline, stage D was defined as “patients with truly refractory HF who might be eligible for specialized, advanced treatment strategies, such as MCS, procedures to facilitate fluid removal, continuous inotropic infusions, or cardiac transplantation or other innovative or experimental surgical procedures

47. Fluid restriction (1.5 to 2 L/d) is reasonable in stage D, especially in patients with hyponatremia , to reduce congestive symptoms .

48. Ionotropes : Until definitive therapy ( eg , coronary revascularization, MCS, heart transplantation) or resolution of the acute precipitating problem, patients with cardiogenic shock should receive temporary intravenous inotropic support to maintain systemic perfusion and preserve end-organ performance.

49. Cardiac transplant: Evaluation for cardiac transplantation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management

50. Management of Heart failure 1. Initial and serial evaluation of the HF pt 2. Treatment through stages A to D 3. Acute Heart Failure

51. ACUTE HEART FAILURE ESC guidelines for diagnosis and treatment of acute HF

52. AHF Definition: Rapid onset or change in signs and symptoms of heart failure, resulting in the need of urgent therapy. It may present as new HF or worsening HF in presence of chronic HF

53. Diuretic tit-bits Bumetanide – most potent Torsemide – longest T ½ (24 hr action) Drug interactions: Thiazide /loop diuretic with Digitalis – hypokalemia casing digitalis toxicity ACEi with spironolactone – hyperkalemia can cause cardiac arrest in diastole. (* hypercalcemia causes cardiac arrest in systole ) loop diuretic with aminogylcoside – ototoxicity Spironolactone in HF heart failure (provided CrCl >30 mL /min and serum K <5 mEq / dL )

54. Some new drugs in HF management Nesiritide : Synthetic form of BNP Causes natriuresis and diuresis Rapidly metabolized by vasopeptidase (a neutral endopeptidase ) thus given in infusion Carperitide : ANP analogue Uralitide : Analogue of Urodilatin which is a peptide like ANP and BNP

55. Ompatrilat & Sampatrilat : Inhibits neutral endopeptidase Also inhibits ACE Levosimendan & Pimobendan : Ca sensitisers Has phosphodiesterase III blocking property ( levosimendan ) Isteroxine : Na K atpase pump (like digitalis)

56. Cinacigaut : Nitrates act by stimulating guanyl cyclase to produce NO for vasodilatation In guanyl cyclase resistant people direct stimulaton by this compound Aka Bay compounds

57. studied in 12 patients with severe congestive heart failure and compared with those of dopamine in 10 clinically similar patients. Dobutamine produced a distinct increase in cardiac index, while lowering left ventricular end-diastolic pressure and leaving mean aortic pressure unchanged. Dopamine also significantly improved cardiac index, but at the expense of a greater increase in heart rate than occurred with dobutamine . Because it has comparatively little effect on heart rate and aortic pressure, both major determinants of myocardial oxygen consumption, it may be of special value in patients with the low output syndrome associated with coronary heart disease

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