1) HFpEF is the most common form of heart failure, affecting over 70% of heart failure patients over age 65. It is associated with substantial morbidity and mortality. 2) HFpEF is challenging to diagnose because ejection fraction is normal and cardiac congestion is difficult to evaluate non-invasively. It is defined hemodynamically as a clinical syndrome associated with a lack of capacity of the heart to pump blood adequately without elevated cardiac filling pressures. 3) There is currently no effective pharmacological treatment for HFpEF. Treatment focuses on controlling congestion through diuretics, managing comorbidities, and promoting exercise. Future efforts to better characterize HFpEF phenotypes may allow individualized therapies

1. Evaluation and
management of HFpEF

3. Nature Reviews | Cardiology 30TH 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 Obesity, METs, and T2DM
4. Diagnosis of HFpEF - Challenging because ejection fraction is
normal; Cardiac congestion is difficult to evaluate non-invasively and
many patients have hemodynamic abnormalities only during exercise.

4. • 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 30TH MARCH 2020

5. Characterization of HFpEF, HFmrEF, and
HFrEF

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

8. Cardiac Causes of Dyspnea that may Mimic HFpEF

9. Mechanisms of HFpEF

10. Low physical activity = High
HFpEF risk

11. The aging heart = HFpEF = low grade
fibrosis

13. Cardiac magnetic resonance and
the complex pathophysiology of
HFpEF

14. Myocardial histopathologic findings in
HFpEF

15. 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

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

17. Mentz, JACC 2014

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

19. The many faces of HEpEF

21. HFpEF is Extremely Comorbid

22. HFpEF and Non- Cardiac Comorbidities

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

25. tzman D, Shah SJ. JACC 2016; Borlaug B. Nat Rev Cardiol

26. HFpEF and cardiac Comorbidites

29. EF: Multiple pathologies, multiple comorbidit
Senni M, Pieske B. EHJ 2014

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

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

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

35. “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”

36. 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

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

38. HFpEF symptoms and signs : women vs. men

39. The Two Faces of Heart Failure

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

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

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

43. haracterization of Subgroups of Heart Failure
Patients with Preserved Ejection Fraction
P et al European Journal of Heart Failure (2015) 17, 925-935

45. Comorbidity clusters in ASIAN-HF

47. Consider Alternative Diagnoses

49. Adapted from Tromp J et al., JAHA 2017
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5
hs-CRP (mg/L)
Pentraxin-3 (ng/mL)
RAGE (ng/mL)
NT-proBNP (ng/mL)
VEGFR (ng/mL)
HFpEF
HFrEF
Total cohort
0 5 10 15 20 25
proANP (ng/mL)
HFpEF
HFrEF
Total cohort
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.

54. HFpEF diagnosis by a clinical score
eddy Y et al. Circulation 20

55. Summary : The new HFA HF-PEE2
SCORE

57. 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 o
Haemodynamic exercise test
INTEGRATED Diagnostic
Approach for HFpEF
Nature Reviews | Cardiology 30TH MARCH 2020

60. Current Treatment of
HFpEF

62. Major randomized clinical trials of pharmacological
treatments for HFpEF

63. Major randomized clinical trials of pharmacological treatments fo

66. Outcome trials in HFpEF and (HFmrEF)

68. RAAS Inhibition in HFpEF

76. Diuretic Use in HFpEF

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

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

90. PARAGON - HF: key inclusion criteria

94. Non-pharmacological therapy
Complete revascularization- CAD with HFpEF Pts.
HFpEF with AF– CATHETER ABLATION
Therapies targeting cardiometabolic r
Exercise training
Sodium restriction
Weight loss
Caloric restriction
SGLT2I can improve clinical outcomes in patients with HFpEF
Nature Reviews | Cardiology 30TH MARCH 2020

95. Device-based therapies
1. Strategy of rate-adaptive atrial pacing is currently
being tested in the RAPID-HF trial.
2. Percutaneously implanted intra-atrial septostomy
device- studied
3. Opening the anterior pericardium through a minimally
invasive subxiphoid approach-currently being tested
No device-based therapy has been approved for
HFpEF.
Nature Reviews | Cardiology 30TH MARCH 2020

96. Senni M et al. Eur
Heart J 2014

98. 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

99. Future 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 ofMRAs, managementof
comorbidities and promotion of a healthy active
lifestyle, with prescription of exercise training
where feasible.
Nature Reviews | Cardiology 30TH MARCH 2020