HeART FAILURE Hfpef

Hfpef

1. Evaluation and management of HFpEF

2. Nature Reviews | Cardiology 30 TH MARCH 2020 Introduction – Incidence & Prevalence 1. HFPEF- the most common form of HF , associated with substantial morbidity and mortality. At present >70% of patients with HF aged >65 years have HFpEF . 2. The incidence and prevalence of HFpEF has been growing by 10% every 10 years relative to HFrEF. 3. This gap is expected to widen owing to the ageing of the general population and the increasing prevalence of conditions associated with the development of HFpEF, particularly O besity, METs, and T2DM 4. Diagnosis of HFpEF - C hallenging because ejection fraction is normal; C ardiac congestion is difficult to evaluate non-invasively and many patients have hemodynamic abnormalities only during exercise.

3. • 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

4. Characterization of HFpEF , HFmrEF , and HFrEF

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

6. Cardiac Causes of Dyspnea that may Mimic HFpEF

7. Mechanisms of HFpEF

8. Low physical activity = High HFpEF risk

9. The aging heart = HFpEF = low grade fibrosis

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

11. Myocardial histopathologic findings in HFpEF

12. Mechanisms in HFpEF -- Six mechanisms are outlined —three hemodynamic (orange) and three cellular/molecular (grey).Data for cardiometabolic abnormalities are largely from other animal models and HFrEF , but hypothesized to be applicable toHFpEF . European Heart Journal (2018) 39, 2780–2792

13. European Journal of Heart Failure (2018) 20, 216–227

14. Mentz, JACC 2014

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

16. The many faces of HEpEF

17. HFpEF is Extremely Comorbid

18. HFpEF and Non- Cardiac Comorbidities

19. Potential extracardiac mechanisms involved in HEpEF K Sharma and DA Kass . Circ Res. 2014;115:79-96

20. Kitzman D, Shah SJ. JACC 2016; Borlaug B. Nat Rev Cardiol

21. HFpEF and cardiac Comorbidites

22. HEpEF : Multiple pathologies, multiple comorbidities Senni M, Pieske B. EHJ 2014

23. Major causes of mortality differ in HFpEF vs. HFrEF

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

25. What is HFpEF ? How do we make the diagnosis?

26. “Huffing & Puffing” (dyspnoea & exercise intolerance) are most common symptom. “Huff – Puff” “To complain noisily about something but not be able to do anything about it”. Clinician may approach HFpEF with diagnostic & therapeutic nihilism & consider there patient as untreatable and difficult to manage because of lack of guidelines & treatment options. Diagnosis & treatment of HFpEF requires diligence hypervigilance. 59 HFpEF: “Huff Puff”

27. 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

28. Similar Signs and Symptoms in Patients with HFpEF and HFrEF

29. HFpEF symptoms and signs : women vs. men

30. The Two Faces of Heart Failure

31. “Preserved EF” it does not mean “preserved” systolic function in HFpEF Kralgher-Krainer et al., JACC 2014

32. *average from septal and lateral e’ **LV global longitudinal strain ***depending on software package

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

34. Characterization of Subgroups of Heart Failure Patients with Preserved Ejection Fraction Kao DP et al European Journal of Heart Failure (2015) 17, 925-935

35. Comorbidity clusters in ASIAN-HF

36. Consider Alternative Diagnoses

37. Adapted from Tromp J et al., JAHA 2017 Angiogenesis, P = 0.009 Cardiomyocyte stretch, P < 0.001 Inflammation , P = 0.053 Inflammation , P = 0.009 Inflammation , P = 0.001 Cardiomyocyte stretch, P = 0.002 Pathophysiological process and uncorrected P value Biomarker levels in HFpEF and HFrEF patients 33 Biomarkers were measured. Only biomarkers that were significantly differently expressed between HFpEF and HFrEF are indicated. J AM HEART ASSOC. 2017;6:E003989.

38. HFpEF diagnosis by a clinical score Reddy Y et al. Circulation 20

39. Summary : The new HFA HF-PEE2 SCORE

40. Patient with unexplained dyspnoea Assessment of pre-test probability: clinical evaluation +ECHO H2 FPEF score HFA-PEFF score Low probability, unlikely HFpEF (H2FPEF score of 0–1, HFA-PEFF score of 0–1) Intermediate probability (H2FPEF score of 2–5, HFA-PEFF score of 2–4) High probability, likely HFpEF (H2FPEF score of 6–9, HFA-PEFF score of 5–6) Haemodynamic exercise test INTEGRATED Diagnostic Approach for HFpEF Nature Reviews | Cardiology 30 TH MARCH 2020

41. Current Treatment of HFpEF

42. Major randomized clinical trials of pharmacological treatments for HFpEF

43. Major randomized clinical trials of pharmacological treatments for HFpEF

44. Outcome trials in HFpEF and ( HFmrEF )

45. RAAS Inhibition in HFpEF

46. Diuretic Use in HFpEF

47. Predicted effectiveness of sacubitril/valsartan (arrows) across the heart failure spectrum European Journal of Heart Failure (2020) doi:10.1002/ejhf.1837

48. PARAMOUNT: Designed in Parallel With PARADIGM-HF to Provide Pilot Data for Sacubitril/Valsartan in HFpEF

49. NTproBNP in PARAMOUNT (n=301 – Phase 2 Proof of Efficacy) Most compelling evidence to date for development of treatment for HFpEF

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

51. PARAMOUNT: Improvement in Left Atrial Size and NYHA Class With Sacubitril/Valsartan at 36 Weeks

52. PARAGON-HF: Trial Design

53. PARAGON - HF: key inclusion criteria

54. 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

55. Device-based therapies 1. S trategy of rate-adaptive atrial pacing is currently being tested in the RAPID-HF trial. 2. P ercutaneously implanted intra-atrial septostomy device- studied 3. Opening the anterior pericardium through a minimally invasive s ubxiphoid approach- currently being tested N o device-based therapy has been approved for HFpEF . Nature Reviews | Cardiology 30 TH MARCH 2020

56. Senni M et al. Eur Heart J 2014

57. Hypertension Obesity Coronary microvascular and macrovascular disease Diabetes mellitus and metabolic syndrome LV dysfunction only LV and LA dysfunction and/or atrial fibrillation Pulmonary vascular dysfunction RV dysfunction LVFP with exercise only Pulmonary vasodilatation with exercise LVFP at rest with pulmonary hypertension RVFP and LVFP at rest Arterial stiffness Endothelial and coronary microvascular dysfunction Sarcopenia and mitochondrial dysfunction Tissue fibrosis Normal natriuretic peptide levels Pro-inflammatory markers Cardiac injury markers Fibrotic markers Phenotyping in patients with HFpEF

58. F uture efforts to more rigorously characterize and group patients into discrete phenotypes hold great promise to allow the individualization of therapy to improve outcomes. 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 MRAs, management of comorbidities and promotion of a healthy active lifestyle, with prescription of exercise training where feasible. Nature Reviews | Cardiology 30 TH MARCH 2020