Management of heart failure

Management of heart failure

1. Evaluation and management of Heart Failure Presenter Under Guidance of Dr. Ajay Tripathi Dr. Vimlesh Patidar Sir Dr. Ashish Sharma Sir 1

2. Heart Failure HF as a complex clinical syndrome that results from structural or functional impairment of ventricular filling or ejection of blood , which in turn leads to the cardinal clinical symptoms of dyspnea and fatigue and signs of HF, namely edema and rales. 2

3. Etiology A ny condition that leads to an alteration in Ventricular structure or function can predispose a patient to developing HF. 3

4. Pathogenesis HF is a progressive disorder that is initiated after an index event either damages the heart muscle, with a resultant loss of functioning cardiac myocytes, or, alternatively, disrupts the ability of the myocardium to generate force, thereby preventing the heart from contracting normally. This understanding holds for HFrEF For HFpEF our understanding still evolving, with diastolic Dysfuntion seen as primary mechanism 4

5. Period of Compensation 1) A ctivation of the renin-angiotensin-aldosterone system (RAAS) 2) increased myocardial contractility 3) A family of countervailing vasodilatory molecules are activated, including the atrial and brain natriuretic peptides (ANP and BNP ), bradykinin , prostaglandins (PGE2 and PGI2), and nitric oxide (NO), that offset the excessive peripheral vascular vasoconstriction 5

6. HF Clinical Manifestation Symptoms Dyspnea & Fatiuge Orthopnea , Noctural cough PND , Cardiac Asthama Others Anorexia , Nausea, Early satiety, Abdominal pain and fullness Cheyne strokes respiration– Apnic phase– Hyperventilation-- Apnic 6

7. HF Clinical Manifestation Signs SBP – reduced or high in early HF, generally reduced in Advanced HF Jugular Veins– RA pressure estimation, >8cm or + HepetoJugualr Ref Pulmonary Examination- Bibasilar End Exp Fine rales, can be absent Rochi can be heard due to bronchospasm (Cardiac Asthma) Cardiac Exam- cardiomegaly, diffuse or sustained apex, S3 gallop, Murmers of MR/TR due to chamber dilation Peripheral dependent pitting edema Cardiac Chechexia 7

8. Classification of HF severity As by AHA/ACC , heart failure classified as: 1) HFrEF – With EF <40% on 2D ECHO Study, systolic HF 2) HFpEF – With EF>50% on 2D ECHO Study, Diastolic HF Patients with EF 41-49% are sometimes reffered as HFmEF (Mid Range ) include overlapping cases representing both groups, mostly they show characters of HFpEF 8

9. NYHA Functional Classification 9

10. Stages in the development of HF As outlined by American college of Cardiology/AHA stages in HF Stage A – At high risk for HF but without structural heart disease or symptoms of HF . Stage B – Structural heart disease but without signs or symptoms of HF. This stage includes patients in NYHA functional class I with no prior or current symptoms or signs of HF. Stage C – Structural heart disease with prior or current symptoms of HF. This stage includes patients in any NYHA functional class (including class I with prior symptoms). Stage D – Refractory HF requiring specialized interventions. This stage includes patients in NYHA functional class IV with refractory HF. 10

11. HFpEF – Heart failure with preseved Ejection Fraction 11

12. • HFpEF is defined hemodynamically as a clinical syndrome associated with a lack of capacity of the heart to pump blood adequately without the requirement for elevated cardiac filling pressures. ACC/AHA/HFSA and the ESC continue to use an ejection fraction ≥50% as the threshold to identify HFpEF DEFINITION Nature Reviews | Cardiology 30 TH MARCH 2020 12

13. 13

14. Diastolic dysfunction versus HFpEF  — Diastolic dysfunction and HFpEF are not synonymous terms . Diastolic dysfunction indicates a functional abnormality of diastolic relaxation, filling defect, or distensibility of the LV, regardless of whether the LVEF is normal or abnormal and whether the patient is symptomatic or not. HFpEF denotes the signs and symptoms of clinical HF in a patient with a normal LVEF and LV diastolic dysfunction. Diastolic dysfunction alone is essentially part of normal human aging and is seen in many people that do not or never will have HFpEF . 14

15. Mechanisms of HFpEF 15

16. Remodelling Adaptive vs Maladaptive Its Both By Adaptation it allows heart to maintain function in response to pressure or volume overload in the acute phase of cardiac injury P rogressive remodeling is deleterious and associated with a poor prognosis 16

17. 17

18. Myocardial Remodelling Concentric Remodelling charaterised by:- ● A normal or near-normal end-diastolic volume . ● Increased wall thickness and/or LV mass . ● An increased ratio of myocardial mass to cavity volume . ●An increased relative wall thickness (RWT). The RWT is defined as either 2 x (posterior wall thickness) / (LV diastolic diameter)  or  as (septal wall thickness + posterior wall thickness) / (LV diastolic diameter ). 18

19. Cardiomyocyte and extracellular matrix remodeling Myocytes show inc thickness and no inc in length, Chamber vol remain same and mass inc There is Myocardial Fibrosis Slow delayed and incomplete LV filling 19

20. Establised Risk Factors Pathophysiology HFrEF 20

21. Low physical activity = High HFpEF risk 21

22. The aging heart = HFpEF = low grade fibrosis 22

23. Cardiac magnetic resonance and the complex pathophysiology of H FpEF 23

24. Myocardial histopathologic findings in HFpEF 24

25. The many faces of HEpEF 25

26. Heart Failure With Preserved Ejection Fraction In Perspective, Volume: 124, Issue: 11, Pages: 1598-1617, DOI: (10.1161/CIRCRESAHA.119.313572)

27. 27

28. HFpEF is Extremely Comorbid 28

29. HFpEF and Non- Cardiac Comorbidities 29

30. HF a Spectrum? 30

31. European Heart Journal Advance Access published November 3, 2015 31

32. Predominant phenotypes in male & female with HFpEF Bourlag B et al. EHJ 2016 32

33. Diagnosis

34. 35

35. 1. Symptoms of heart failure: - Dyspnea – Orthopnea - Paroxysmal nocturnal dyspnea – Fatigue - Reduced exercise capacity. 2. Signs of heart failure on physical examination: - Jugular venous distention -Positive hepatojugular reflux - Lower extremity edema - Displaced point of maximal apical impulse - S3 heart sound. 3. Echocardiography – LVEF ≥50 % and at least one ECHO finding:- - Diastolic dysfunction – LAA or LVH - Left atrial volume Index >34 mL/m2 - Left ventricular mass index greater than or equal to: 115 g/m2 in male patients ;95 g/m2 in female patients - E/e’ greater than or equal to 13 4. Elevation of natriuretic peptides -B-type natriuretic peptide >35 pg /ml - NTpro -BNP >125 pg /ml Diagnostic Criteria REF—US Cardiology Review 2018;12(1):8-12. DOI:10.15420/usc.2017:21:1 36

36. Causes of the clinical syndrome of HFpEF-not to be regarded as true HFpEF Treatment considerations distinct from primary HFpEF Diagnostic tools Etiology 37

37. HFpEF diagnosis by a clinical score Reddy Y et al. Circulation 20  A low H 2 FPEF score of 0 or 1  is associated with Low probability of HFpEF 38

38. 39

39. Current Treatment of HFpEF Symptomatic treatment with diuretics ? Spirolactone ?SGLT2 Inhibitors Treatment of Hypertension Rate control for AF Treat Ischemia 40

40. Major randomized clinical trials of pharmacological treatments for HFpEF 41

41. Major randomized clinical trials of pharmacological treatments for HFpEF 42

42. 43

43. 44

44. Outcome trials in HFpEF and ( HFmrEF ) 45

45. 46

46. The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial comparing spironolactone with placebo showed a non-significant 11% reduction in a combined primary endpoint of cardiovascular death, aborted cardiac arrest or HF hospitalization, but there was a significant reduction in HF hospitalizations overall 47

47. 48

48. Paramount Trial 49

49. PARAMOUNT: Significant Reduction in NT-proBNP With Sacubitril/Valsartan at 12 Weeks 50

50. SGLT2 inhibitor Empagliflogen , in “EMPEROR-Preserved” trial concluded in July 2021 , has shown benificial effects in HFpEF “ Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes” P- 0.05 51

51. Diuretic Use in HFpEF 52

52. Senni M et al. Eur Heart J 2014 53

53. Non-pharmacological therapy Complete revascularization- CAD with HFpEF Pts. HFpEF with AF – CATHETER ABLATION Therapies targeting cardiometabolic risk E xercise training Sodium restriction W eight loss C aloric restriction SGLT2I can improve clinical outcomes in patients with HFpEF Nature Reviews | Cardiology 30 TH MARCH 2020 54

54. . CONCLUSION HFpEF has grown to become the dominant form of HF worldwide and continues to present a diagnostic and therapeutic challenge. Treatment of HFpEF is aimed at control of congestion and involves the use of Diuretics , MRAs, SGLT2 inhibitors management of comorbidities and promotion of a healthy active lifestyle, with prescription of exercise training where feasible. Nature Reviews | Cardiology 30 TH MARCH 2020 55

55. HFrEF Heart failure with reduced Ejection Fraction 56

56. Pathophysiology of heart failure with reduced ejection fraction: Hemodynamic alterations and remodeling Frank Starling Law Ventrical End diastolic volume Stroke Volume relationship 57

57. A Failing heart More After load dependent for stroke volume An reduction of afterload by drugs like Nitrates , ACEI , ARNI increases stroke volume and decrease remodelling Eccentric remodelling and Ventricular dilation leads to HFrEF / Volume overload 58

58. Cellular Level Remodelling M yocyte hypertrophy, L oss of myocytes due to apoptosis N ecrosis Fibroblast proliferation Fibrosis Neuro hormonal activation as response 59

59. Diagnosis - Symptoms:   Dyspnea on exertion, fatigue, weight gain - Signs:  Peripheral edema , rales - Chest radiograph:  Findings consistent with cardiomegaly or pleural effusion - ECG:  Atrial fibrillation (AF), left atrial enlargement, LV hypertrophy, or pathologic Q waves - Echocardiogram:  If EF <50% Left atrial volume index >34 mL/m2, E/A ≥0.9 and <2.1,  or  E/A ≤0.8 and E >50 cm/s 60

60. - Serum natriuretic peptide: Age <50: N-terminal pro-B-type natriuretic peptide (NT- proBNP ) 125 to 450 pg /mL or BNP 35 to 100 pg /mL Age 50 to 75: NT- proBNP 450 to 900 pg /mL or BNP 35 to 100 pg /mL Age >75: NT- proBNP 900 to 1800 pg /mL or BNP 35 to 100 pg /mL Clinical feature:  Coronary artery disease (including prior myocardial infarction), or moderate valvular regurgitation or stenosis 61

61. Management Principals HFrEF Some Abbreviations.. GDMT : Guideline-directed medical therapy, representing treatment options supported for use by clinical practice guidelines. Optimal therapy : Treatment provided at either the target or the highest-tolerated dose for a given patient. Target dose : Doses targeted in clinical trials. 62

62. Principle 1: GDMT is the foundation of HF care , and the GDMT with the highest expected benefit should be Prioritized. Principle 2: Target doses are associated with best outcomes. 63

63. Initiating Guideline Directed Medcial Therapy (GDMT) for HFrEF , Principal Guidelines Established Therapies-- - ARNIs, ACEIs, ARBs ,BB, Loop Diuretics, MRAs, HYD/ISDN Excepting Loop Diuretics all improve symptoms, reduce hospitalizations, and/or prolong survival . ARNIs are the preferred , but for patients in whom ARNI administration is not possible, an ACEI/ARB is recommended. Use of digoxin as a treatment for HFrEF lacks new data current role- as a rate control agent for AF in those with low BP. Initiation of a beta-blocker is better tolerated when patients are dry and an ACEI/ARB/ ARNI when patients are wet. Only evidence-based beta-blockers should be used. 64

64. Management HFrEF As Per 2021 Updates of AHA/ ACC 65

65. Stages in the development of HF As outlined by American college of Cardiology/AHA stages in HF Stage A – At high risk for HF but without structural heart disease or symptoms of HF. Stage B – Structural heart disease but without signs or symptoms of HF. This stage includes patients in NYHA functional class I with no prior or current symptoms or signs of HF. Stage C – Structural heart disease with prior or current symptoms of HF. This stage includes patients in any NYHA functional class (including class I with prior symptoms). Stage D – Refractory HF requiring specialized interventions. This stage includes patients in NYHA functional class IV with refractory HF. 66

66. A B C ARNI ACEI/ARB Evidence-based BB If previously on ACEI, ensure 36 hours off before initiation Consider in patients where ARNI administration is not possible Select initial dose of beta-blocker: SELECT STARING DOSE 24/26 mg–49/51 mg twice daily ;MAINTENACE DOSE 97/103 mg twice daily Select initial dose of ACEI or ARB: Consider increasing dose of BB every 2 weeks until maximum tolerated or target dose is achieved Monitor HR, BP, and for signs of congestion after initiation and during titration If patient is taking equivalent of ≤10 mg daily of enalapril or equivalent of ≤ 160 mg daily of valsartan: 24/26 mg twice daily If patient is taking equivalent of >10 mg daily of enalapril or equivalent of >160 mg of valsartan: 49/51 mg twice daily In 2 weeks, assess tolerability If possible, increase dose stepwise to target of 97/103 mg twice daily Monitor blood pressure, electrolytes, and renal function after initiation and during titration Treatment Algorithm For GDMT Including Novel Therapies 67

67. D E F Diuretics Aldosterone antagonists SGLT2 inhibitor Select initial loop diuretic dose: Initial dose depends on multiple factors, including renal function and prior exposure to diuretic therapy Select initial dose of aldosterone antagonist: Select dapagliflozin or empagliflozin: 10MG/day Titrate dose to relief of congestion over days to weeks. In some instances it may be necessary to reduce diuretic dosing in the setting of increasing doses of ARNI/ACEI/ARB Monitor BP , electrolytes, and renal function after initiation and during titration If reaching high doses of loop diuretic (i.e., equivalent of 80 mg of furosemide twice daily), consider: a. changing to a different loop diuretic Or b. adding thiazide diuretic, taken together with loop diuretic Monitor BP, electrolytes, and renal function after initiation and during titration Consider increasing dose of aldosterone antagonist at least every 2 weeks until maximum tolerated or target dose is achieved Monitor electrolytes (especially potassium) and renal function at 2-3 days following initiation, and then 7 days after initiation/titration Then, check monthly for 3 months and every 3 months afterwards Ensure eGFR ≥30 ml/min/1.73 m2 for dapagliflozin and eGFR ≥ 20 ml/min/1.73 m 2 for empagliflozin before initiation Treatment Algorithm For GDMT Including Novel Therapies 68

68. G Hydralazine + isosorbide dinitrate Select initial dose of hydralazine and isosorbide dinitrate , either as individual medications or fixed-dose combination: Consider increasing dose of hydralazine and/or isosorbide dinitrate every 2 weeks until maximum tolerated or target dose is achieved .Monitor blood pressure after initiation and during titration Treatment Algorithm For GDMT Including Novel Therapies 69

69. H Ivabradine Reassess that BB are adjusted to maximally tolerated doses and/or target doses Verify patient is in sinus rhythm Select starting dose of ivabradine : Age ≥ 75 years : 2.5 mg twice daily with food Age < 75 years : 5 mg twice daily with food Reassess heart rate in at least 2-4 weeks Heart rate <50 beats/min or symptoms of bradycardia Heart rate 50-60 beats/min Heart rate >60 beats/min Reduce dose by 2.5 mg twice daily with food or discontinue if already at 2.5 mg twice daily with Food Monitor heart rate Maintain current dose and monitor heart rate Increase by 2.5 mg twice daily with food until reaching maximum dose of 7 .5 mg twice daily with food Monitor heart rate Treatment Algorithm For GDMT Including Novel Therapies 70

70. HFrEF Stage C Trt ARNI/ACEI/ARB* (ARNI preferred; AND evidence-based BB # with diuretic agent as needed For patients with eGFR ≥:30 ml/min/1.73 m2 or creatinine ≤2.5 mg/dl in males or ≤ 2.0 mg/dl in females or K+ ≤ 5.O mEq /L NYHA Class ll·IV For patients meeting eGFR criteria , NYHA class II-IV For patients with persistent volume overload, NYHA class II-IV For persistently symptomatic Black patients despite ARNI/BB/MRA /SGLT2 inhibitor, NYHA class III-IV For patients with resting HR ≥ 70, on maximally tolerated BB dose in sinus rhythm, NYHA class II-III Add Add Titrate Add Add MRAs SGLT2I Diuretic HDN +ISDN Ivabradine Treatment Algorithm For GDMT Including Novel Therapies Light Green color - Class I therapy Light yellow color Class II therapy. * ACEl /ARB should only be considered in patients with contraindications, intolerance or inaccessibility to ARNI. #Carvedilol, metoprolol succinate, or bisoprolol. 71

71. Adjustment of therapies ---Every 2 weeks. Aim - To achieve optimal GDMT within 3 to 6 months of an initial diagnosis of HF. Follow-up-- - Frequent reassessment of the clinical status of the patient, BP, and kidney function (and electrolytes) should be performed. Reassessment of ventricular function- - S hould occur 3 to 6 months after target (or maximally tolerated) doses of GDMT are achieved to determine the need for device therapies such as ICD /CRT . HIGH risk for sudden death -- The time to follow-up imaging might be shorter (e.g., 3 months), whereas in those at lower risk , time to follow-up might be longer (e.g., 6 months) Summary for Initiation and Titration of HFrEF Therapies 72

72. Recent data suggests that directly initiating an ARNI, rather than a pretreatment period ACEI or ARB, is a safe and effective strategy. P atients with de novo HF who underwent in-hospital initiation of an ARNI had a greater reduction in Natriuretic Peptides concentrations, a comparable safety profile, and a significant improvement in early clinical outcomes compared with those on enalapril . When de novo initiation of ARNI is performed , close follow-up and serial assessments (blood pressure, electrolytes, and renal function) should be considered, and any such usage should consider concerns regarding the risk of angioedema or hypotension . About one-half of the patients could achieve the target dose within 10 weeks after in-hospital initiation or soon after discharge Initiation of an ARNI De Novo Without Prior Exposure to an ACEI or ARB –Preferred ?- 73

73. The initiation of ARNI in hospitalized ADHF pts feasible after the patient has been hemodynamically stabilized and not volume –depleted In patients with Borderline blood pressure (e.g., SBP <=100 mm Hg), careful administration and follow-up are advised. Renal function and potassium should be checked within 1-2 weeks of initiation or dose up-titration of ACEI/ARB/ARNI. In non congested patients with otherwise stable clinical profiles, empiric modest lowering of loop diuretic agents has been found to mitigate the hypotensive effects of sacubitril/valsartan. Angiotensin Receptor-Neprilysin Inhibitor (ARNI)- issue ? 74

74. TABLE --- Indications for ARNI, Ivabradine, and SGLT2 Inhibitor Use Indications for Use of an ARNI HFrEF (EF ≤ 40%) NYHA class II–IV HF Administered in conjunction with a background of GDMT for HF in place of an ACEI or ARB Indications for Use of Ivabradine HFrEF (EF ≤ 35%) On maximum tolerated dose of beta-blocker Sinus rhythm with a resting heart rate ≥ 70 beats/min NYHA class II or III HF Indications for Use of an SGLT2 Inhibitor HFrEF (EF ≤ 40%) with or without diabetes NYHA class II–IV HF Administered in conjunction with a background of GDMT for HF 75

75. Severe Mitral Regurgitation and the Use of Transcatheter M V Repair GDMT has to optimized before referral for the procedure to ensure the greatest likelihood that patients will receive the combined benefits of optimal GDMT together with edge-to-edge repair. Surgical treatment is recommended in cases of severe primary chronic MR resulting in HFrEF Transcatheter mitral valve repair may be considered among symptomatic patients with chronic moderate-severe to severe mitral regurgitation despite optimal doses of all GDMTs 76

76. When life expectancy is short (<1 year) due to other comorbidities, implantable devices may not be appropriate. NYHA class IV and Stage D HF being considered for advanced therapies may not be appropriate Patients in Whom New Therapies May Not Be Indicated 77

77. Starting and Target Doses of Select GDMT and Novel Therapies for HF Starting Dose Target Dose Beta-Blockers Bisoprolol 1.25 mg once daily 10 mg once daily Carvedilol 3.125 mg twice daily 25 mg twice daily for weight ≤85 kg and 50 mg twice daily for weight ≥85kg Metoprolol succinate 12.5–25 mg daily 200 mg daily ARNIs Sacubitril /valsartan 24/26 mg–49/51 mg twice daily 97/103 mg twice daily ACEIs Captopril 6.25 mg 3x daily 50 mg 3x daily Enalapril 2.5 mg twice daily 10–20 mg twice daily Lisinopril 2.5–5 mg daily 20–40 mg daily Ramipril 1.25 mg daily 10 mg daily ARBs Candesartan 4–8 mg daily 32 mg daily Losartan 25–50 mg daily 150 mg daily Valsartan 40 mg twice daily 160 mg twice daily Aldosterone antagonists Eplerenone 25 mg daily 50 mg daily Spironolactone 12.5–25 mg daily 25–50 mg daily SGLT2 inhibitors Dapagliflozin 10 mg daily 10 mg daily Empagliflozin 10 mg daily 10 mg daily 78

78. CONTD Starting and Target Doses of Select GDMT and Novel Therapies for HF Starting Dose Target Dose Vasodilators Hydralazine 25 mg 3 x daily 75 mg 3 x daily Isosorbide dinitrate † 20 mg 3 x daily 40 mg 3 x daily Fixed-dose combination isosorbide dinitrate /hydralazine‡ 20 mg/37.5 mg (1 tab) 3 x daily 2 tabs 3 x daily Ivabradine Ivabradine 2.5–5 mg twice daily Titrate to heart rate 50–60 beats/min. Maximum dose 7.5 mg twice daily * Use of digoxin as a treatment for HFrEF lacks new data ( current role- as a rate control agent for AF in those with low BP ) †Isosorbide mononitrate is not recommended by the ACC/AHA/HFSA guideline. ‡The ACC/AHA/HFSA guideline considers either the fixed-dose combination or the separate combination of isosorbide dinitrate and hydralazine as appropriate guideline-directed therapy for HF. 79

79. TABLE Dose Adjustments of Sacubitril /Valsartan for Specific Patient Populations Population Initial Dose High-dose ACEI > Enalapril 10-mg total daily dose or therapeutically equivalent dose of another ACEI 49/51 mg twice daily High-dose ARB > Valsartan 160-mg total daily dose or therapeutically equivalent dose of another ARB De novo initiation of ARNI Low- or medium-dose ACEI ≤ Enalapril 10-mg total daily dose or therapeutically equivalent dose of another ACEI 24/26 mg twice daily Low- or medium-dose ARB ≤ Valsartan 160-mg total daily dose or therapeutically equivalent dose of another ARB ACEI/ARB naïve Severe renal impairment* ( eGFR <30 mL/min/1.73 m 2 ) Moderate hepatic impairment (Child-Pugh Class B) Elderly (age ≥75 years) *This population was not studied in the PARADIGM-HF trial. The statement is consistent with FDA-approved labeling indications. PARADIGM-HF = Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in HF. 80

80. TABLE Recommended Starting Dose of Ivabradine Population Initial Dose Maximally tolerated beta-blocker dose with persistent resting heart rate ≥70 beats/min 5 mg twice daily with meals History of conduction defects Age ≥ 75 years 2.5 mg twice daily with meals 81

81. TABLE Contraindications and Cautions for Sacubitril/Valsartan, A) Sacubitril /Valsartan Contraindications Cautions Within 36 hours of ACEI use History of angioedema with or without an ACEI or ARB Pregnancy Lactation (no data) Severe hepatic impairment (Child-Pugh C) Known hypersensitivity to either ARBs or ARNIs Renal impairment: Mild-to-moderate ( eGFR 30-59 mL/ min/1.73 m2): no starting dose adjustment required Severe (eGFR <30 mL/min/ 1.73 m2): reduce starting dose to 24/26 mg twice daily; double the dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily, as tolerated Hepatic impairment: Mild (Child-Pugh A): no starting dose adjustment required Moderate (Child-Pugh B): reduce starting dose to 24/26 mg twice daily; double the dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily, as tolerated Renal artery stenosis SBP <100 mm Hg Volume depletion 82

82. TABLE Contraindications and Cautions for Ivabradine B) Ivabradine Contraindications Cautions HFpEF Presence of angina with normal EF Hypersensitivity Severe hepatic impairment (Child-Pugh C) Acute decompensated HF Blood pressure <90/50 mm Hg Sick sinus syndrome without a pacemaker SA node block 2nd or 3rd degree block without a pacemaker Resting HR <60 beats/min Persistent AF or flutter Atrial pacemaker dependence Sinus node disease Cardiac conduction defects Prolonged QT interval 83

83. TABLE Contraindications and Cautions for SGLT2 inhibitors C) SGLT2 Inhibitors Contraindications Cautions Not approved in T1DM due to increased risk of diabetic ketoacidosis Known hypersensitivity to drug Lactation (no data) On dialysis For HF care, dapagliflozin , eGFR <30 mL/min/1.73 m2 Dose 10mg OD For HF care, empagliflozin, eGFR <20 mL/min/1.73 m2 Dose 10mg OD Pregnancy Increased risk of mycotic genital infections May contribute to volume depletion. Consider altering diuretic dose if applicable Ketoacidosis in patients with diabetes: Temporary discontinuation before scheduled surgery is recommended to avoid potential risk for ketoacidosis Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level Acute kidney injury and impairment in renal function: consider temporarily discontinuing in settings of reduced oral intake or fluid losses Urosepsis and pyelonephritis: evaluate patients for signs and symptoms of UTI and treat promptly, if indicated Necrotizing fasciitis of the perineum (Fournier’s gangrene): rare, serious, life-threatening cases have occurred in both female and male patients; assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise 84

84. Barriers to Medication Titration 1. Abnormal renal function and/or hyperkalemia / established renal disease 2. A decrease in eGFR of >30% or the development of hyperkalaemia -- dose reduction required 3 In hypovolemia , the dose of diuretic agents should be reduced 4. The ARNI dose may also need to be reduced in the setting of renal insufficiency or hypotension 5. Monitoring should be dictated by the clinical stability of renal function and volume status 6 . Below-target doses of multiple classes of GDMT are likely more effective in reducing risk than large doses of 1 or 2 agents. 85

85. Scenario1: Worsening renal function or hyperkalemia-- Use less than target doses of an ARNI/ACEI/ARB and discontinue MRA if estimated creatinine clearance <30 ml/min or serum potassium >5.0 mEq /L . Scenario2: ----Symptomatic hypotension May be due to over-diuresis/ use of non-CV drugs with hemodynamic effects. All of these should be addressed before deciding to lower doses of evidence-based therapies Tolerability and side effects 86

86. Testing and Medication Titration Following Diagnosis of HFrEF Studies to Consider Initially: • BNP/NT- proBNP • CBC, basic metabolic panel, liver function, iron studies, thyroid studies, HbA 1c • EKG • Chest X-ray • ECHO • Coronary angiogram, cardiac MRI, biopsy, other imaging as appropriate Serial Evaluation and Titration of Medications Clinic visit with history/symptoms, vitals, exam, labs If volume status requires treatment, adjust diuretics, follow up 1-2 weeks If euvolemic and stable, start/increase/switch GDMT, follow up 1-2 weeks via virtual visit or repeat clinic visit with basic metabolic panel as may be indicated Repeat cycle until no further changes are possible or tolerated Lack of response/instability End-Intensification/maintenance Ongoing assessment Additional adjustments as indicated Repeat objective data as needed to reestablish prognosis Remember acronym to assist in decision-making for referral to advanced heart failure specialist: I-NEED-HELP I: IV inotropes N: NYHA IV or persistently elevated natriuretic peptides E: End-organ dysfunction E: Ejection fraction ≤35% D: Defibrillator shocks H: Hospitalizations >1 E: Edema despite escalating diuretics L: Low blood pressure, high heart rate P: Prognostic medication: progressive intolerance or down-titration of GDMT Assess response to therapy and cardiac remodeling Repeat laboratory tests, for example, BNP/NT- proBNP and basic metabolic panel Repeat ECHO (or similar imaging modality for cardiac structure and function) Repeat EKG Consider EP referral for those eligible for CRT or ICD Intensification 2-4 months (1-4 week cycles) Stabilization ~ 3 months 87

87. Biomarkers—When to Order NP Class I recommendation to measure BNP or NT- proBNP to support a clinical diagnosis of HF, assess disease severity, or establish prognosis Always interpret NP in the context of GDMT ; Caution -- When attempting to interpret BNP values in the context of ARNI treatment, and NT- proBNP measurement may be preferable in this setting Guidelines -- upper limit of normal in a non-acute setting is 35 pg /ml for BNP and 125 pg /ml for NT- proBNP . In the acute setting, the cut-off values are higher at 100 pg /ml for BNP and 300 pg /ml for NT- proBNP . 88

88. Heart failure with Rhythm abnormality Primary prevention with ICD and CRT should be considered after consistent use of optimal doses of all GDMTs for at least 3 to 6 months, followed by reassessment of EF and other indications for device therapy, which include pharmacological rhythm control /rate control strategy as indicated. 89

89. DISCUSSIONS AND IMPLICATIONS OF PATHWAY— Management of HFrEF often involves multidisciplinary care. GDMT would be expected to significantly benefit affected patients. No guideline, pathway, or algorithm should ever supersede clinical judgment—as clinical practice guidelines continue to evolve. Conclusion 90

90. ADHF – Acute Decompensated Heart Failure 91

91. Acute Decompensated Heart Failure ADHF heterogeneous syndrome Its clinical syndrome of new or worsening signs and symptoms of HF, often leading to hospitalization or a visit to the emergency department Among ADHF 70% admission due to worsening Chronic HF 15% due to HF for the first time  5 percent are admitted for advanced or end-stage HF . Amoung all <8% has Low BP and 3% in Cardiogenic shock 92

92. M ajor causes for new onset ADHF CAD ACS Arrhythmias Myocarditis Acute valve syndrome Progressive valve disease Cardiomyopathies Uncontrolled Hypertension/Emergency , Urgency with HF 93

93. Clinical Manifestation Mild to moderate ADHF Progressive dyspnea , Peripheral/ Andominal cogestion signs Hypertensive ADHF Virtually all pts are HFpEF BP often >180 Major signs of Pulmonary rather systemic congestion Radiological and pulmonary signs on auscultaion ADHF with severe pulmonary edema   Orthopnea severe Pul congestion and sys congestion signs Type 1 resp Failure due to congestion, Radiological and Auscultatory signs 94

94. High-output heart failure   Uncommon cause of ADHF Presents with  warm extremities, pulmonary congestion, tachycardia, and a wide pulse pressure. Underlying conditions include anemia, thyrotoxicosis, advanced liver failure 95

95. Diagnosis On History , clinical signs and symptoms Diagnosis is supported by appropriate investigations, such as ECG, chest radiograph, biomarkers (B-type natriuretic peptide [BNP] or N-terminal proBNP [NT- proBNP ]), and Doppler echocardiography  Most dyspneic patients with HF have plasma BNP values above 400  pg / mL. For patients <50, 50 to 75, and >75 years of age, the optimal plasma NT- proBNP cutoffs for diagnosing HF are 450, 900, and 1800  pg /mL, respectively 96

96. Management Principal Outlines Initial evaluation for cardiopulmonary instability- quick , brief, establish status of hemodynamic stability status Establish causative factor eg ACS etc Patients with respiratory failure and/or shock- Require inotropic support , and ventilatory support ACS- Require thrombolysis , cardiac catheterization with coronary angiography etc 97

97. Cardio-Renal Syndrome Recognised as complication of ADHF Approx 30% patient with HF , develop renal abnormalities Pathophysiology– PreRenal Azotemia , backpressure failure imparing renal venous blood flow , renal congestion and ischemia 98

98. Cardio-Renal Syndrome.. Classification Type 1 (acute)  – Acute HF results in acute kidney injury (previously called acute renal failure). ● Type 2  – Chronic cardiac dysfunction ( eg , chronic HF) causes progressive chronic kidney disease (CKD, previously called chronic renal failure). ● Type 3  – Abrupt and primary worsening of kidney function due, for example, to renal ischemia or glomerulonephritis causes acute cardiac dysfunction, which may be manifested by HF. ● Type 4  – Primary CKD contributes to cardiac dysfunction, which may be manifested by coronary disease, HF, or arrhythmia. ● Type 5 (secondary)  – Acute or chronic systemic disorders ( eg , sepsis or diabetes mellitus) that cause both cardiac and renal dysfunction. 99

99. Diagnosis Normal Urine analysis No e/o past underlying kidney disease before advent of Heart Failure Worsening of Renal biochemiacal tests 100

100. Management If BUN/Cr ratio is high and e/o sys congestion is present , diuretic therapy must continue Improvement in cardiac function   - left ventricular assist devices (LVADs) and cardiac resynchronization therapy Inotropic support Drug modification and reconsideration Ultrafiltration (CARRESS-HF Trials) 101

101. Take Home Message Heart failure understanding is evolved as a complex pathophysiological syndrome, management should be guided by guidelines Management of HFrEF often involves multidisciplinary care. GDMT would be expected to significantly benefit affected patients. No guideline, pathway, or algorithm should ever supersede clinical judgment—as clinical practice guidelines continue to evolve. 102

102. Thank you 103

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104. Thus ECHO criteria Diastolic dysfunction / HFpEF - LVEF ≥50 % and at least one ECHO finding:- - Diastolic dysfunction – LAA or LVH E/e” Ratio >13 (reflects LVEDP) Systolic Dysfuntion / HFrEF - LVEF<50% and E/A ≥0.9 and < 2.1,  or  E/A ≤0.8 and E >50 cm/s 105

105. 2d ECHO parametres in diagnosing HF 106

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107. 108 Apical Four chamber view

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120. 121 What happens to E/A ratio?

121. 122 Here A>E

122. 123 Pseudo Normal Pattern/ ?Restrictive pattern

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132. 133 Summary

133. Thus ECHO criteria Diastolic dysfunction / HFpEF - LVEF ≥50 % and at least one ECHO finding:- - Diastolic dysfunction – LAA or LVH E/e” Ratio >13 (reflects LVEDP) Systolic Dysfuntion / HFrEF - LVEF<50% and E/A ≥0.9 and < 2.1,  or  E/A ≤0.8 and E >50 cm/s 134

134. Cor - Pulmonale

135. Cor - Pulmonale Definition- Referred as Pulmonary heart disease , defined by altered RV structure &/or function in context of chronic lung disease and is triggered by presence of pulmonary hypertension Pathophysiology – Pulmonary HTN developing due to chronic lung pathology , leading to inc RV afterlaod , RV dilation , with or without hypertrophy

136. Etiology Massive pulmonary embolism is the most common cause of acute cor pulmonale . A massive pulmonary embolism can mimic a myocardial infarction with elevated troponins, ST changes, chest pain, and shortness of breath. Chronic obstructive pulmonary disease (COPD) is the most common cause of cor pulmonale .. In most patients with COPD, cor pulmonale tends to be accompanied by mild pulmonary hypertension (i.e., mean pulmonary artery pressure 40 mmHg or less)

137. Clinical Manifestation Dyspnoea – usually due to inc work of breathing due to fibrosis and changes in lung parenchyma Lower extremity edema Hepatic congestion , hepetomegaly , leading to chronic abd pain , abd girth inc due to ascits Signs of Pul HTN S3 gallop, RV Heave JVP with prominent V wave indicative of TR Narrow split S2 as pul valve closes earlier due to High Pul pressure

138. Diagnosis History , signs , symp , Chest Xray 2D Echo- RV wall thickness , RV chamber diameter Doppler for Pul Art pressure Septum paradoxical movement in systoli may be seen Calculated measures of RV function CT Angio for diagnosing Acute Pul Emboli & Chronic thromboembolic disease Electrocardiogram: Shows features of right ventricular hypertrophy/enlargement Cardiac catherisation can comfirm diagnosis of Pul Htn and can exclude elevated Left sided pressure as cause of HF BNP, proBNP levels are elevated due to RV stretch

139. Management Aimed at treating underlying condition Oxygenation improve hypoxic pul vasoconstriction Diuretics to dec RV Preload Vasodilators CCB like Nifidipine / Dilzem to reduce Pul pressure Cardiac Glycoside , Modest Effect , controversial Theophylline – Bronchodilator effects, dec Pul Vascular resistance

140. Right-sided heart failure   This syndrome of predominantly right-sided HF a/w severe isolated tricuspid regurgitation, right ventricular dysfunction, chronic lung disease, eg chronic obstructive lung disease, interstitial lung disease, or long-standing pulmonary hypertension