it highlights new concept in cardiology

1. Diastolic Heart Failure: A new
enemy in Cardiology
Dr. Rahul arora

2. Outline
• Introduction to Diastolic Heart Failure/Heart Failure with Preserved
Ejection Fraction
• Evolving definitions of HFpEF
• Complex Integrated pathophysiologic mechanisms of HFpEF
• Exploring reasons of failed interventions for HFpEF
• Understanding Current management with a clinical case.
• Conclusion

3. Outline
• Introduction to Diastolic Heart Failure/Heart Failure with Preserved
Ejection Fraction
• Evolving definitions of HFpEF
• Complex Integrated pathophysiologic mechanisms of HFpEF
• Exploring reasons of failed interventions for HFpEF
• Understanding Current management with a clinical case.
• Conclusion

4. HFpEF-A Road less travelled
1980s
HF exclusively Systolic
dysfunction
RCTs included only
reduced EF
patients
Subsequent data on
Normal EF HF
(Diastolic HF)
HFrEF <40%
HFpEF >50%
HFmrEF 40-49%
Half of total HF cases have HFpEF
No Proven therapy that has shown reduction in
Morbidity & Mortality for HFpEF

5. Prevalence of HF-PEF
Secular Trends 1987-2001 - Olmstead county
Owan et al, NEJM, 2006
1 9 8 6 1 9 9 0 1 9 9 4 1 9 9 8 2 0 0 2
20
30
40
50
60
70
r = 0.9 2 ; p < 0.0 0 1
%HFpatientswithHF-PEF
38% 54%

6. What is HFpEF?
• Challenges associated with HFpEF begin with its definition
• The definition of HFpEF has evolved over the last 2 decades
• Moving from echocardiographic evidence of diastolic dysfunction in
the setting of an EF>50%, towards a definition including cardiac
structural abnormalities resulting from
• high filling pressures,
• diastolic abnormalities,
• elevated biomarkers,
• elevated left heart filling pressures by invasive hemodynamic assessment

7. Outline
• Introduction to Diastolic Heart Failure/Heart Failure with Preserved
Ejection Fraction
• Evolving definitions of HFpEF
• Complex Integrated pathophysiologic mechanisms of HFpEF
• Exploring reasons of failed interventions for HFpEF
• Understanding Current management with a clinical case.
• Conclusion

8. Diagnosis of HFpEF- Evolution of its definition

9. Outline
• Introduction to Diastolic Heart Failure/Heart Failure with Preserved
Ejection Fraction
• Evolving definitions of HFpEF
• Complex Integrated pathophysiologic mechanisms of HFpEF
• Exploring reasons of failed interventions for HFpEF
• Understanding Current management with a clinical case.
• Conclusion

10. Risk Factors
Age is a risk factor for HF, and the incidence of HFpEF increases more dramatically with age
than the incidence of HFrEF
When other HFpEF risk factors (age, obesity, blood pressure, current treatment for hypertension, and
previous myocardial infarction) are adjusted for, women are not at a higher risk of HFpEF than men
Exposure to ionizing radiation therapy—even at the low cardiac doses resulting from contemporary breast
cancer radiotherapy—has been shown to increase the risk of HFpEF

11. HEpEF- A Single disease entity or many
different diseases?
Limitations
in systolic
reserve
changes in
body
compositio
n
chronotropic
incompetenc
e
left atrial
function
vascular
function
skeletal
muscle
function
Age
associated
changes
Single disease Entity
Multiple disease Entity
nitric oxide
bioavailability

12. Outline
• Introduction to Diastolic Heart Failure/Heart Failure with Preserved
Ejection Fraction
• Evolving definitions of HFpEF
• Complex Integrated pathophysiologic mechanisms of HFpEF
• Exploring reasons of failed interventions for HFpEF
• Understanding Current management with a clinical case.
• Conclusion

13. Promising interventions failed to demonstrate a
definitive benefit in HFpEF patients ?
Failed trial designs or Inefficacious study interventions ?

14. Morphological and functional heterogeneity in
HFpEF Clinical Trials
Should the interventions be studied in a broad group of subjects or in
small group subjects focusing on individual subpopulations ?

15. • To date, HFpEF clinical trials have also adopted broad inclusion
criteria.
• Ensuring adequate statistical power to detect signals may be
especially important in HFpEF trials, given the many comorbid
conditions in HFpEF, which may influence clinical endpoints beyond
HF severity and therapeutic effect.
• The right patients need to be matched to the therapies from which
they are most likely to benefit

16. Ongoing set of studies target unique mechanistic
hypotheses but not specific subphenotypes

17. Subpopulation: at-risk/metabolic disorders-
Impact of preventive interventions in HFpEF vs HFrEF
• Prevention, or delay in progression, of HFpEF may be effective in high-
risk populations
SGLT-2 inhibitors
showing reduced
HF incidence in
Type 2 DM with
CVD

18. Subpopulation: elevated left atrial pressure
However, there's a sizable base of evidence that inorganic nitrate or nitrite administration promote
favorable nitric oxide (NO) effects on vascular function
The only subgroups to show signs of a positive effect from nitrite intake were those who entered the study
with higher levels of brain-type natriuretic peptide (BNP) and the nearly half of the cohort who were in atrial
fibrillation (AF)
Further studies using a variety of inorganic nitrite/nitrate formulations are ongoing

19. Should outcomes for HFpEF be different from
HFrEF

20. Outline
• Introduction to Diastolic Heart Failure/Heart Failure with Preserved
Ejection Fraction
• Evolving definitions of HFpEF
• Complex Integrated pathophysiologic mechanisms of HFpEF
• Exploring reasons of failed interventions for HFpEF
• Understanding Current management with a clinical case.
• Conclusion

21. Clinical Case Vignette
• A 73-year-old woman with a history of dyspnea on exertion presents for a follow-up visit
after hospitalization for acute worsening of dyspnea and orthopnea.
• On admission to the hospital, the patient had atrial fibrillation with a ventricular rate of
120 beats per minute,
• CXR= pulmonary venous hypertension.
• Continues to have fatigue and exertional dyspnea, despite anticoagulation, rate control
with a beta-blocker, and administration of loop diuretics during the hospitalization,.
• BMI is 39, PR=76 bpm, and BP160/70 mm Hg.
• JVP distention and lower-extremity edema but no third heart sound, murmurs, or rales.
S.creatinine=1.4 mg/dl, eGFR=37 ml per minute per 1.73 m2 of body-surface area, and NT-
proBNP level 300 pg/ml.
• Echocardiography reveals an EF=70%, a normal left ventricular cavity dimension and wall
thickness, and left atrial enlargement. Doppler echocardiography shows elevated left atrial
pressure (E/e′ ratio, 22) and an estimated pulmonary-artery systolic pressure of 52 mm Hg.

22. Diagnostic algorithm for diastolic heart failure

23. Treatment Algorithm for HFpEF

24. Treatment Algorithm for HFpEF (contd..)

25. Evidence of a reduction in HF hospitalisation, however these were secondary end points
Both angiotensin II receptor blockers and aldosterone receptor antagonists have a class IIb
indication to reduce the risk of HF hospitalisation

26. Strategies to prevent hospital readmissions

27. Clinical Case Vignette
• The dose of diuretics should be increased to reduce the patient’s clinical
congestion.
• For hypertension and renal dysfunction, an ARB should be added and other
agents used as needed to achieve a blood pressure of less than 140/90 mm Hg.
• Educate regarding self-care for heart failure.
• Anticoagulation should be continued. If symptoms persist, a trial of rhythm
control should be considered.
• The patient’s atherosclerotic risk and the presence of coronary disease should be
assessed to guide the use of statins and other treatments for coronary disease.
• Evaluation for sleep apnea may also be reasonable, given her obesity, fatigue,
hypertension, and atrial fibrillation.
• Once stable, exercise and weight-loss programs should be commenced.

28. Outline
• Introduction to Diastolic Heart Failure/Heart Failure with Preserved
Ejection Fraction
• Evolving definitions of HFpEF
• Complex Integrated pathophysiologic mechanisms of HFpEF
• Exploring reasons of failed interventions for HFpEF
• Understanding Current management with a clinical case.
• Conclusion

29. Conclusion
• Given the challenges in the diagnosis of HFpEF, systematic study of
diagnostic techniques and strategies to enhance recognition of HFpEF
are needed.
• The evidence base for existing pathophysiologic paradigms is not
mature. Thus, there is an urgent need for integrated human studies
elucidating the underlying pathophysiology leading to HFpEF and
development of corresponding clinically relevant animal models.
• Promising agents should be targeted for carefully designed phase II
studies using surrogate endpoints

30. Thank you

31. Subpopulation: Pulmonary Vascular Disease
Many HFpEF
patients have PH,
which is
associated with
increased
symptom burden,
hospitalizations,
and mortality and
unique histo-
pathology

32. Subpopulation: Pulmonary Vascular Disease

33. Systematic Approach to the Diagnosis of Heart
Failure with Preserved Ejection Fraction

34. Systematic Approach to the Diagnosis of Heart
Failure with Preserved Ejection Fraction (contd..)

35. Therapeutic approach to diastolic heart failure