Practical approach to HFrEF management

1. INITIATION AND
OPTIMIZATION OF HFrEF
TREATMENT
Under the guidance of
Dr SS KOTHARI SIR
Dr SHOMU BOHRA SIR
Dr RAGHAV BANSAL SIR
Dr SAMEER RANE SIR
Dr PRIYANKA MAM
Dr SPANDAN SIR
Presenter- Dr Pradeep K Bansal

2. OUTLINE
• Introduction
• Reality about GDMT
• Four pillars of HFrEF
• Practical approach to each GDMT
• HF management in specific clinical conditions
• Case based discussion
• Conclusion

3. Introduction
• HFrEF clinical practice guidelines advocate for the use of
“foundational quadruple therapy”.
• The combined use of these therapies can improve life expectancy for
the average 50-year-old patient with HFrEF by a median of 6 years
compared with more limited regimens.*
*Vaduganathan M., Claggett B.L., Jhund P.S., et al. Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with
heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Lancet. 2020;396(10244):121–128
$ Greene SJ, Butler J, Albert NM, et al. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF Registry. J Am Coll Cardiol.
2018;72(4):351–366

4. Heart failure has significant impact on patients, HCP’s and
healthcare systems globally and in India
8-10
million
LARGEST HF
POPULATION1
3 OUT OF EVERY
5 INDIAN
PATIENTS
YEAR MORTALITY RATE
5
WORSENING HF IS
ONE OF THE MOST
IMPORTANT CAUSE
OF DEATH9
HOSPITALIZATION MORTALITY CAUSE OF DEATH
DISEASE BURDEN1-6
1. Chaturvedi V, Parakh N, Seth S, Bhargava B, Ramakrishnan S, Roy A,et al. Heart failure in India: The Indus (India Ukieri Study) study. J PractCardiovasc Sci 2016;2:282.
Harikrishnan S, et al.. Eur J Heart Fail. 2015;17:794–800. 3. Lam CS, et al. Eur Heart J. 2016;37:3141–3153. 4. Harikrishnan S, et al.Am Heart J. 2017;189:193–199. 5. Pokharel Y, et
al.Clin Cardiol. 2016;39:145–149. 6. Dokainish H, et al. Lancet Glob Health. 2017;5:e665–e672. 7. Chopra VK, et al. Medanta Heart Failure Registry. Unpublished Data (Personal
communication). 8. Kirkwood FA, et al. Am Heart J. 2005;149:209–216. 9. Harikrishnan, Sivadasanpillai et al.International Journal of Cardiology, Volume 326, 139 - 143
1 out of 5
of HFrEF PATIENTS
RE-HOSPITALIZED FOR HF
AT 1-YEAR
INDIAN HF PATIENTS
ARE YOUNGER BY 10-
YEARS, MAJORITY OF
THE BURDEN LIES
BELOW 65YEARS OF
AGE 2-8
CAD IS THE MOST
COMMON ETIOLOGY
FOR HF IN INDIA (AS PER
THE THFR AND
MEDANTA REGISTRY),
RHD IS ALSO A MAJOR
CONTRIBUTOR 6,7
MEDIAN SURVIVAL TIME
3.1 YEARS9

5. HF IN INDIA
* Findings from the National Heart Failure Registry of India (2022)

6. Median survival in patients with
HF
after each hospitalisation*,1
56% of patients are rehospitalised within
30 days of the worsening HF event, and
the number of HFHs increase with time2
*After the initial worsening HF event, each subsequent event becomes longer in duration and is separated by shorter intervals.
HF, heart failure; HFH, heart failure hospitalisation.
1. Setoguchi S et al. Am Heart J. 2007;154:260–266; 2. Butler J et al. J Am Coll Cardiol. 2019;73:935–944;
Second
hospitalisation
(n=3358)
First
hospitalisation
(n=14,374)
Fourth
hospitalisation
(n=417)
Third
hospitalisation
(n=1123)
4.0
3.0
3.5
2.0
2.5
1.0
1.5
0.5
0
Median
survival
(years)
Two hospitalizations already – the risk
is high and increasing

8. • Real-world data from multple registries around the
world suggest that health care providers infrequently
add GDMT and do not titrate baseline HFrEF
medication doses despite the absence of clinical
contraindications or circumstances.
• Significant time delay in optimizing gdmt with
sequential dosing.
• Initiation of multiple therapies upfront facilitates
gdmt optimization later

9. CLINICIANS INERTIA: BIGGEST
PROBLEM

10. Much of the benefit of these foundational treatments was apparent within the first
30 days after randomization .
These findings demonstrate that postponing treatment initiation might cause
unnecessary clinical events, and subsequently, therapy with all four drug classes should,
therefore, be achieved as early as possible

11. START ALL 4 MORTALITY REDUCING DRUGS WITHOUT
DELAY
RRR=73% , ARR=26%, NNT=4

13. Is there any best sequence?
Comparison of ESC-HF 2016 and 2021 recommendations for medical treatment of HeFREF (adapted from Packer and
McMurray, 2020; and Straw et al, 2021)6,7. ESC – European Society of Cardiology, HF – Heart Failure, HeFREF – Heart Failure and a Reduced Ejection Fraction

14. PRACTICALAPPROACH TO EACH GDMT

15. MANAGEMENT OF FLUID RETENTION

16. • Persistent volume overload may compromise
the effectiveness of neurohormonal
antagonists.
• Important to find adequate dose of diuretic
that maintain patient euvolemic.
• Document dry weight.

19. Diuretic resistance and management
• Moderate doses of loop diuretics do not achieve
the desired reduction of extracellular fluid
volume.
Factor for diuretic resistance
Braking phenomenon
Post diuretic sodium retention.
Loss of renaL responsiveness to endogenous
natriuretic peptides.
Hypertrophy and hyperplasia of renal epithelial
cells.

21. • Sequential nephron blockade – eg.
metalozone 2.5-10mg/day, thiazide diuretics

22. • Vasopressin antagonist (tolvaptan ) –
In clinically significant hypervolemic and
euvolemic hyponatremia (Na <125)
• Carbonic anhydrase inhibitors –
To correct metabolic alkalosis that occurs as
contraction phenomenon in response to
diuretics.

23. ACE inhibitors/ARBs/ARNI

24. Initiation criteria :-
• SBP >100 mmHg for 6 h
• No use of IV vasodilator or increase in dose of IV
diuretics in the preceding 6 h
• No use of inotropes in the preceding 24 h
• eGFR >45 ml/min/1.73 m2
• K <5.0 mEq/l
• Fluid retention can attenuate the effects of ACEIs,
so first optimize the dose of diuretics.
• Reduce dose of diuretics before starting to
prevent symtomatic hypotension.

25. Up-titration strategy :-
• Direct initiation of ARNI preferred strategy
• If SBP 100–120 mmHg initiate sacubitril/valsartan
24/26 mg twice daily.
• If SBP >120 mmHg initiate sacubitril/valsartan
49/51 mg twice daily.
• Double dose every 1–2 days as tolerated until
target dose reached or initiation of next pillar of
GDMT.

26. Potential contraindications :-
• K >5.5 mEq/l
• Creat >2.5mg/ml
• SBP<90 mm hg

27. Clinical considerations :-
• If SBP is <100 mmHg throughout
hospitalization, prior to discharge,trial on
equivalent of valsartan 20 mg twice with
intent to switch to ARNI when tolerated
• No use of ACEi in preceding 36 h.
• Side effect of ACEIs like nonproductive cough
(10%-15%) and angioedema (1%).

28. ARNI
Dalal, J., Chandra, P., Ray, S. et al. Practical Recommendations for the Use of Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in Heart
Failure: Insights from Indian Cardiologists. Cardiol Ther 12, 445–471 (2023). https://doi.org/10.1007/s40119-023-00323-8

29. Some important recommendations for
ARNI
Dose titration
• Over 3 weeks for 100 mg bd starting dose and 6 weeks for 50
mg BD starting dose with tolerable profile.
• More gradual in low-dose ACEI/ARB patients
In-hospital initiation of ARNI
• Initiation of sacubitril/valsartan to be feasible in patients with
HFrEF who had stabilized after an acute heart failure event.

30. De novo ARNI
• Starting directly on ARNI is safe and effective with improved cardiac
function and tolerability and is recommended with monitoring and
assessment considering the risk of angioedema or hypotension.
ARNI with SGLT2 inhibitor
• ARNI may be combined with SGLT2i for the treatment of heart failure.
Whenever diuretics are used, the dosage needs to be adjusted.
Modification for hepatic dysfunction patients
• In HF patients with moderate hepatic impairment (Child–Pugh B), the
loading dose of ARNI should be halved and the subsequent doses should
be gradually increased to reach the maximum tolerated dose

31. CKD
• ARNI can be prescribed to non-dialysis patients with CKD and heart
failure.
Decline in renal function on starting ARNI
• Determine the cause of the decline, and if creatinine increases less
than 30% from baseline, ARNI can continue. Adjust or discontinue
ARNI and investigate underlying causes if creatinine exceeds
baseline by 30%. Discontinue ARNI if creatinine exceeds baseline by
50%.

32. Beta blocker
• Metoprolol and bisoprolol –block beta 1 receptor but bisoprolol
have more high affinity to beta 1 receptor.
• Carvedilol block alpha 1, beta 1 &2
• Nebivolol beta 1 blocker with additional vasodilatory properties(not
FDA approved for HFrEF)

33. Initiation criteria :-
• No hypoxia, symptomatic hypotension, or
evidence of shock
• Initiation of beta blocker may lead to wor
sening fluid retention because of abrupt
withdrawal of adrenergic support to heart and
circulation.
• Optimize dose of diuretic before starting it
• Titration should be more gradually (2-3 weeks)
than ACEIs.
• ACEIs followed by Beta blocker (CIBIS -III).

35. Up-titration strategy :
• If SBP 90-120 mmHg or <85 kg start equivalent
of carvedilol 3.125 mg twice daily
• If SBP >120 mmHg or >85 kg start equivalent
of carvedilol 6.25 mg twice daily
• Increase dose as tolerated until target dose
reached.

36. Clinical considerations :
• If shock, severe pulmonary edema or SBP <90
mmHg, hold β-blocker and reinitiate at lowest
dose.
• Always ensure patient is adherent to outpatient
β-blocker before continuing dose
• Younger and heavier patients may tolerate more
aggressive dosing
• Caution in patients with pulmonary disease

37. Initiation criteria :
• On at least minimum dose RAAS-I and β-
blocker
• SCr <2.5 mg/dl in men, <2.0 mg/dl in women
• K <5.0 mEq/l
• No symptomatic hypotension

38. Up-titration strategy :
• Initiate at equivalent of spironolactone 12.5 mg
daily after the initiation of β-blockers and
increase weekly
• Eplerenone initiated at dose of 25mg/day and
increased upto 50 mg daily
Potential contraindications :
• K >5.5 mEq/l, SCr >2.5 mg/dl in men, SCr >2.0
mg/dl in women

39. Clinical considerations :
• Recheck of serum potassium within 7 days
and within 1–2months.
• Consider addition of potassiumbinder if K >5.0
mEq/l
• Painful gynecomastia in 10% to 15% with
spironolactone ,in which case eplerenone may
be substituted.

40. • Finrenone
Selective ,nonsteroidal MRA tested in FIDELIO-
DKD and FIGARO-DKD trial.
It is recommended in patients with T2DM and
CKD.

42. SGLT2 inhibitor
• chfs_practical_approach_algorithm_sglt2i.pdf

43. • Sick day rules for dapagliflozin /
empagliflozin:
Stop during acute illness especially if too unwell
to eat and drink. Stop 3 days prior to major
surgery. Restart when fully recovered and eating
and drinking normally.

44. • In-Hospital Initiation
Simultaneous or clustered initiation of therapies may
improve allocation of guideline-directed therapies
• ARNI or SGLT2i First?
co-administration of ARNI and SGLT2i is anticipated to
be safe and additive
• Need for Background Metformin
SGLT2i are anticipated to be considered first-line
therapy for patients with T2DM and established HFrEF.

48. Ivabradine
• Considered in symptomtic patients with
LVEF≤35%,SR,resting HR ≥70bpm despite
treatment with an evidence based or
maximum tolerated dose of beta blocker or
contraindications for beta blocker.
• Start with 5mg BD uptitrate to 7.5mg BD.
• Can cause visual disturbance .

49. Hydralazine and isosorbide dinitrate
• In black patients with LVEF≤35% , NYHA III-IV
despite treatment with GDMT.
• In symptomatic HFrEF who cnnot tolerate any
of ACEI/ARB/ARNI .
• Start with 37.5mg/20mg TDS tritrate upto
75mg/40mg TDS.

50. DIGOXIN
• HFrEF with AF with FVR when other
therapeutic options cannot be pursued.
• Narrow therapeutic window
• 0.125 to 0.25mg per day
• Serum digoxin level should be <1.0ng/ml

51. Anemia in HF

54. Management of anaemia and iron deficiency in
patients with heart failure
• Periodically screened for anaemia and iron deficiency
with a full blood count, serum ferritin concentration,
and TSAT
• Intravenous iron supplementation with ferric
carboxymaltose should be considered in
symptomatic HF patients recently hospitalized for HF
and with LVEF <45% with serum ferritin <100 ng/ml
with TSAT <20%.

56. Pre-discharge and early post-discharge follow-up of patients
hospitalized for heart failure
• Carefully evaluated to exclude persistent signs
of congestion before discharge and to
optimize oral treatment
• Evidence-based oral medical treatment be
administered before discharge
• An early follow-up visit is recommended at 1-2
weeks after discharge to assess signs of
congestion, drug tolerance and start and/or
uptitrate evidence-based therapy

58. Patient education, self-care and
lifestyle advice
• Explanation about HF
• Medication
• Implanted devices
• Activity and exercise
• Sleep and breathing
• Fluids
• Healthy diet
• Immunization

60. Monitoring with biomarkers
• Larger randomized trials have now been
published, with the largest being TIME-CHF,
with 500 patients with systolic HF followed for
18 months. This reported a 24% reduction in
all-cause mortality and a 30% reduction in HF
hospitalization, but neither of these effects
reached statistical significance.

61. Potential natriuretic peptide-guided management of chronic heart failure
(modified from the TIME-CHF protocol

62. CASE 1
69 yr old male with old acs sev lvd with cad dvd on
gdmt p/w acute lvf with h/o recurrent admission ,
BP-100/60

63. • 2d echo –
Ef-global 25% , apex akinetic, aneurysmal
LA-54mm
Mild MR
Dd/Ds-65/52 mm
Lab – hb-10.4, creat-2.5, k-4.5, bnp- 35000

64. On following prescription

67. Issue in this patient-
• AF
• AKI
• Scar myocardium
• Renal stone

68. CASE 2
41 year k/c/o DCMP ,recurrent admission for failure
,h/o cva , come to HF clinic with NYHA III dysnoea

69. Tab eliquis 5 mg BD
Tab vymada 50 mg BD
Tab tide plus 10/25 od
Tab dapa 5mg od
Tab metxl 25 bd

70. Issue in this patient-
• LV clot
• LBBB
• h/o CVA
• Financial issue

71. CASE 3
57 yr old male patient h/o chb
underwent PPI (VVI) in 2006 then PGR
in 2018, then he develop lV dysfuction
with severe MR , CAG was insignificant
not relieved with HF medication,
undergone CRT-P in 2019.
better snce 2022..last 1 yr recurrent
admission with failure

72. At present ecg

73. Ecg in march

75. Severe TR , mild MR , EF global 20%

76. Issue in this patient :-
• Severe TR
• QRS width not narrow
• Multiple leads across TV

77. Conclusion

78. THANK YOU