An insight into the current recommendations on management of various types of heart failure.

1. REVIEW ON
RECENT
ADVANCES
IN HEART
FAILURE
PRESENTED BY : Dr. VIKAS GUPTA
MODERATOR : Dr. D.P. BHADORIA

2. DEFINITION AND TYPES
– Complex clinical syndrome that results from structural and
functional impairment of ventricular filling or ejection of
blood, which in turn leads to cardinal clinical symptom of
dyspnoea and fatigue and signs of heart failure (HF), namely
edema and rales.
– Types:
1. Presrved EF (HFpEF) : EF > 50 %
2. Mid-range EF (HFmrEF) : EF 40-50 %
3. Reduced EF (HFrEF) : EF < 40 %

3. ETIOLOGY
Depressed EF
• CAD
• Chronic pressure/volume
overload- HTN, valvular
heart disease, septal defects
• Chronic lung disease
• DCMP
• Toxin/drug induced
• Viral
• Chagas’ disease
• Arrythmias
Preserved EF
• Primary hypertrophic
cardiomyopathies
• Pathologic hypertrophy
secondary to HTN
• Restrictive cardiomyopathy–
amyloidosis, sarcoidosis,
hemochromatosis etc.
• Aging
• Endomyocardial disorders

4. Pathogenesis:
Index event
• Activation of compensatory mechanisms like adrenergic
nervous system, renin angiotensin aldosterone system
and the cytokine system.
Short term
• Restoration of cardiovascular system to normal
homeostatic range, thus patient remains asymptomatic.
Long term
• LV remodelling
• Excessive salt and water retention

5. Biomarkers in heart failure-
useful in cases of clinical
uncertainity
Natriuretic peptides : BNP
and NT-proBNP
Soluble ST-2
Galectin-3

6. Life’s simple 7 by ADA

7. ACUTE DECOMPENSATED
HEART FAILURE
-Rapid onset or worsening of symptoms and/or signs of
HF.
-Heterogeneous clinical syndrome.
- Life threatening medical
condition requiring urgent
hospital admission.
-Associated with excessive
morbidity and mortality.
Decreased cardiac
performance
Alteration in
vascular
compliance.
Renal dysfunction
Confluence of inter
related
abnormalities

8. Factors triggering acute heart
failure:
Arrythmias
Acute
coronary
syndrome
Hyper
tension
Infection
Pulmonary
embolism
Drugs
Metabolic/
hormonal
derangements

9. Parameters associated with
worse outcomes:
–Increased BUN or creatinine
–Hypotension
–Elevated troponin I level.

10. Criteria for hospitalization in
ICU/CCU include any of the
following:
– Need for intubation (or already intubated)
– Signs/symptoms of hypoperfusion
– Oxygen saturation (SpO2) <90%
(despite supplemental oxygen)
– Use of accessory muscles for breathing,
respiratory rate > 25/min
– Heart rate < 40 or > 130 bpm, SBP < 90 mmHg.

11. General principles of
management of ADHF:
Therapeutic goals:
– Volume control
– Decrease of vascular impedance
– Maintaining attention to end-organ
perfusion (coronary and renal).

12. Cardiopulmonary resuscitation-
the very first step
– Immediately provide circulatory support
(pharmacological, mechanical) in patients with
cardiogenic shock and ventilatory support
(oxygen, NIV, mechanical ventilation) in patients
with respiratory failure.

13. Identify and treat precipitants
– Identify and treat known precipitants of
decompensation mainly active infection,
pulmonary thromboembolism,
arrhythmias and ongoing ischemia.

14. As mentioned above that ADHF is a heterogeneous
clinical syndrome, efforts should be made to identify
the phenotypic presentation of ADHF and accordingly
decide the treatment goals.
Acute decompensation
“pulmonary edema”:
Hypoxia is an important
clinical feature.
Acute decompensation
“hypertensive AHF” :
characterized by vascular type
fluid redistribution.
Hypertension is predominant.
Volume overload is not the
usual feature.
Acute decompensation
“low output”: Signs of
hypoperfusion
Acute decompensation
“cardiogenic shock”:
Hypotension with end
organ failure is common.

15. Pulmonary
Edema
•O2 and non-
invasive
ventilation
•Diuretics
•Ultrafiltration
•Vasodilators
•Opiates
Hypertensive
AHF
• Vasodilator
• diuretic
Low output
• Vasodilators
• Inotropic
therapy
Cardiogenic
shock
• Inotropic
therapy
• Mechanical
circulatory
support

16. Recommendations for O2
therapy and ventilatory
support:
– Oxygen therapy is recommended in patients with SpO2
<90% or PaO2 <60 mmHg.
– Non-invasive positive pressure ventilation (CPAP, BiPAP)
should be considered in patients with respiratory distress
(respiratory rate >25 breaths/min, SpO2 <90%).
– Intubation is recommended, if respiratory failure, leading
to hypoxaemia (PaO2 <60 mmHg (8.0 kPa)), hypercapnia
(PaCO2 >50 mmHg (6.65 kPa)) and acidosis (pH <7.35),
cannot be managed non-invasively.

17. Volume management
– Randomized clinical trials of high- versus low-dose or
bolus versus continuous infusion diuresis have not
provided clear justification for the best diuretic strategy in
ADHF.
– Continuous infusion of a diuretic may be useful when large
doses are required or the effect is suboptimal.
– Thus in cases of severe congestion, consider continuous
infusion (not trial supported).
– Reduced toxicity with the use of continuous infusion.
– Continue diuresis until euvolemia has been achieved.

18. – Torsemide has a higher oral bioavailability, thus can be
given orally in advanced heart failure if furosemide
becomes less bioavailable due to gut congestion.
– Role of adjuvant diuretics for augmentation: Addition of a
thiazide diuretic in combination provides a synergistic
effect. Metolazone in doses of 2.5-10 mg can cause severe
electrolyte imbalance.
– Dose of commonly used diuretics: Furosemide: 20-240 mg
daily (maximum dose that can be used in a day: 600 mg);
Torsemide: 10-100 mg daily.

19. Ultrafiltration (UF)
– There is no evidence favouring ultrafiltration over loop
diuretics as first-line therapy in patients with AHF. Role of
ultrafiltration in the management of ADHF is limited to
those patients who are diuretic unresponsive.
– Benefits over diuretics: controlled rates of fluid removal, no
direct neurohormonal activation and neutral effects on
serum electrolytes. Thus, it is also referred to as
aquapheresis. It has also been shown to restore diuretic
sensitivity.

20. Vascular therapy
– Includes iv nitrates, nitroprusside and nesiritide.
– I.V. vasodilators should be considered for symptomatic
relief in AHF with SBP >90 mmHg (and without
symptomatic hypotension).
– In patients with Hypertensive AHF, i.v. vasodilators should
be considered as initial therapy to improve symptoms and
reduce congestion.

21. NESIRITIDE
(recombinant BNP)
• More rapid and greater
reduction in PCWP as
compared to nitrates.
• Side effect is hypotension,
more with bolus dose.
• ASCEND-HF trial concluded
that its use is not
associated with an
increase in rates of death
or rehospitalisation but
Routine use of this drug
cannot be advocated due
to lack of significant
efficacy.
SERELAXIN (recomb.
human relaxin-2)
• There is evidence of
reduced signs and
symptoms of
congestion and lower
rates of
rehospitalization and
cardiovascular mortality
(RELAX-AHF trial).
URODILATIN
(natriuretic peptide)
• Inferior to existing
therapies in terms of
clinical outcome with
higher rate of
hypotension and
worsening serum
creatinine.(TRUE-AHF
trial)

22. Vasodilator Dose Main side effect/
limitation
Nitroglycerine Start with 10-20
µg/min, increase up to
200 µg/min
Hypotension,
headache, tolerance on
continuous use
Isosorbide dinitrate Start with 1 mg/h,
increase up to 10
mg/hour
Hypotension,
headache, tolerance on
continuous use
Nitroprusside Start with 0.3
µg/kg/min and increase
up to 5 µg/kg/min
Hypotension,
isocyanate toxicity
Nesiritide Bolus 2 µg/kg + infusion
0.01 µg/kg/min
Hypotension

23. Inotropic therapy:
– Helps to increase cardiac output, increase blood pressure,
improve peripheral perfusion and maintain end organ
function.
– Mainly indicated in those patients of ADHF who have a low
cardiac output and/or hypotension.
– These agents cause an increase in intracellular
concentration of cAMP, thus increasing cytoplasmic
calcium.
– Drugs in this class include sympathomimetic amines
(Dobutamine) and PDE-3 inhibitor (Milirinone).

24. Recommendations on using
inotropic agents/vasopressors in
patients of ADHF:
– May be considered for short term in patients with hypotension
and/or signs/symptoms of hypoperfusion despite adequate filling
status.
– Inotropic agents are not recommended unless the patient is
symptomatically hypotensive or hypoperfused. Long-term inotropic
therapy increases mortality whereas short-term use is associated with
increased arrhythmia.
– A vasopressor (norepinephrine preferably) may be considered in
patients who have cardiogenic shock, despite treatment with another
inotrope. In such cases, intra-arterial blood pressure measurement
may be considered.
– They are currently indicated as bridge therapy (to either left
ventricular assist device support or to transplant) or as selectively
applied palliation in end-stage heart failure.

25. – An intravenous infusion of levosimendan or a PDE III
inhibitor may be considered to reverse the effect of beta-
blockade if beta-blockade is thought to be contributing to
hypotension with subsequent hypoperfusion.
– It is recommended to monitor ECG and blood pressure
when using inotropic agents and vasopressors, as they can
cause arrhythmia, myocardial ischaemia, and in the case of
levosimendan and PDE III inhibitors, also hypotension.

26. Dobutamine:
• Short acting.
• Variable efficacy in presence of beta-
blockers (requires higher doses).
• Clinical tolerance to prolonged infusions.
• Side effect: hypersensitivity carditis
(rare).
Milirinone:
• Slower acing than dobutamine.
• Renally excreted and thus
requires dose adjustment in in
the setting of renal dysfunction.
• Useful in patients receiving
beta-blockers, it acts
downstream from the beta-1
adrenergic receptor.
• Hypotension is the main side
effect due to vasodilatory action
Levosimendan:
• MOA: myofilament calcium
sensitization rather than increasing
intracellular calcium.
• Also, possess PDE3 inhibitory
activity that is responsible for
vasodilatory action and
hypotension.
• Drug unsuitable in cases of low
cardiac output in the setting of
hypotension.
• REVIVE II, SURVIVE : Modest
improvement in symptoms but no
improvement in all-cause mortality
at 180 days and worsened short-
term mortality and ventricular
arrhythmias

27. Omecamtiv mecarbil :
– Selective myosin activator.
– It does not increase the myocardial
oxygen demand as it does not
increase force of contraction, rather
it prolongs the ejection period and
increases fractional shortening.
– COSMIC-HF trial for chronic heart
failure: Improvement in cardiac
function, LV remodelling indices and
natriuretic peptide expression after
20 weeks.
– ATOMIC-AHF trial in acute heart
failure: Improved outcomes seen
without a concomitant increase in
tachyarrhythmias as compared to
placebo. Adverse event profile and
tolerability of OM similar to those of
placebo.

28. Inotropic
agent
Bolus Infusion rate
Dobutamine No 2-20 µg/kg/min
Dopamine No 3-5 µg/kg/min; inotropic (β)
>5 µg/kg/min : (β), vasopressor
(α)
Milirinone 25-75 µg/kg over 10-20
min
0.375–0.75 μg/kg/min
Levosimendan 12 μg/kg over 10 min
(optional), Bolus not
recommended in
hypotensive patients
0.1 μg/kg/min, which can be
decreased to 0.05 or increased to
0.2 μg/kg/min
Doses of inotropes used to treat acute heart
failure:

29. Role of neurohormonal
antagonism in ADHF:
– PROTECT trial testing selective A1 Adenosine
receptor antagonist Rolofylline and EVEREST
trial testing oral selective vasopressin-2
antagonist
– Tolvaptan have yielded disappointing results.
Tolvaptan may be used to treat patients with
volume overload and resistant hyponatraemia
(thirst and dehydration are recognized adverse
effects).

30. Recommendations on thrombo-
embolism prophylaxis and other drugs
in ADHF:
– Thrombo-embolism prophylaxis (e.g. with LMWH) is
recommended in patients not already anticoagulated and
with no contra-indication to anticoagulation, to reduce the
risk of deep venous thrombosis and pulmonary embolism.
– Digoxin can be considered as first line therapy for acute
control of ventricular rate in patients with atrial fibrillation.
– Opiates may be considered for cautious use to relieve
dyspnoea and anxiety in patients with severe dyspnoea but
nausea and hypopnea may occur.

31. Mechanical Assist Devices:
– In patients of severe persistent systolic heart failure who fail
to respond adequately to optimal medical therapy,
mechanical assist devices may be required.
– These include Intra-aortic balloon pump (IABP) and Left
ventricular assist device (LVAS).
– They either be used for short-term as a bridge to recovery or
to cardiac transplantation (bridge to transplantation) or for
long-term as permanent support for lifetime therapy
(destination therapy).
– Available as a therapeutic option in both acute as well as end-
stage chronic heart failure.

33. Pulsatile
flow system
Continuous
flow system

34. Continuous flow system:
– These LVAS use either axial flow system (HeartMate II) or
the newly developed centrifugal flow system (HeartMate
III).
– Heartmate III has been shown better outcomes
compared to HeartMate III. (MOMENTUM 3 trial).
– HeartMate III is fully implanted in the pericardial space
and does not require an abdominal pump pocket. It is
more hemocompatible, does not exhibit hemolysis or
shear high molecular weight vWF antigen and is not
associated with pump thrombosis.
– 2 year survival >70%; Durability : 5-10 years

35.  Cardiac arrhythmias are another important complication of
these devices.

36. Algorithm for confirmation
of suspected HF
(non-acute onset):

37. Raised levels of natriuretic
peptides : Not always heart
failure.
Cardiac causes
– ACS
– Pulmonary embolism
– Myocarditis
– LVH
– Valvular heart disease
– Congenital heart disease
– Arrythmia
– cardioversion
Non cardiac causes
– Advanced age
– Ischaemic stroke
– SAH
– Renal dysfunction
– Liver cirrhosis with ascites
– COPD
– Sepsis
– Severe burns

38. Management of heart failure
with preserved ejection fraction
(HFpEF):
– Identification and correction of risk factors like
hypertension, ageing, atherosclerosis and diabetes.
– Following should be the general therapeutic principles
while treating a patient of HFpEF:
 Control of congestion
 Stabilization of heart rate and blood pressure.
 Treat and prevent myocardial ischemia
 Detect and treat sleep apnea
 Improvement of exercise tolerance

39. LCZ696
– LCZ696 is commonly known as ARNI (angiotensin receptor-
neprilysin inhibitor).
– It has shown benefits in HFpEF. It enhances myocardial
relaxation and reduces ventricular hypertrophy.
– This dual blocker has been shown to reduce circulating
natriuretic peptides.
– However, PARAGON-HF published on September 2019 did
not show significant difference in the cardiovascular
outcomes when compared with valsartan alone.

40. Patients with HFpEF have impaired exercise tolerance, commonly
accompanied by augmented blood pressure response to exercise and
chronotropic incompetence. Rate-responsive pacing has been designed to
increase heart rate according to metabolic needs during physical, mental or
emotional activity. Increased body movement (vibrations) and/or increased
rate of breathing act as signals.

41. None of the trials done for HFpEF come out a with a
better therapeutic option.
TRIAL DRUG TESTED RESULT
CHARM Candesartan Reduction in hospitalization, but no
reduction in mortality
I-PRESERVE Irbesartan No decrease in rate of death of
hospitalization
TOPCAT Spironolactone No improvement in mortality or
hospitalization
ALDO-DHF Spironolactone No improvement in exercise capacity,
symptoms or QOL measures.
SENIORS Nebivolol No benefit in cardiovascular or all-cause
mortality
DIG Digoxin Not effective
RELAX Sildenafil No improvement in functional capacity or
QOL
NEAT-HF Isosorbide
mononitrate
No improvement in QOL or exercise capacity

42. SUMMARY OF THE
TREATMENT IN HFpEF
– Excessive use of vasodilators or diuretics may lead to hypotension and
syncope due to excessive decrease in preload.
– Targeted therapy like RAAS directed therapy, digoxin, beta-blockers,
PDE-5 inhibitors or nitrates is ineffective.
– ARNIs show early promise.
– Evaluation for and correction of underlying ischemia is beneficial.
– Appropriate identification and treatment of sleep-disordered breathing
should be strongly considered.
– Use of rate responsive pacemakers in patients having impaired exercise
tolerance may be beneficial.

43. Management of Heart
Failure with Reduced
Ejection Fraction
(HFrEF)

45. NEUROHORMONAL
ANTAGONISM
– Neurohormonal antagonism with RAAS blockers
and beta-blockers form the cornerstone of
disease modifying therapy in the patients with
HFrEF.
– These drugs reduce symptoms, improve QOL,
decrease rehospitalization and reduce mortality
(due to pump failure or arrhythmia).
– These drugs lead to attenuation of decline and
improvement in cardiac structure and function.

46.  ACEIs cause a 23% reduction in mortality and a 35%
reduction the combined endpoint of mortality and
hospitalizations.
 Patients treated with beta-blockers provide a further 35%
reduction in mortality on top of the benefit provided by
ACEI alone.
 ACEIs and beta-blockers are also recommended in patients
with asymptomatic LV systolic dysfunction to reduce the
risk of HF development.
 Use of ACEI is generally safe in patients with mild renal
insufficiency and use of beta-blockers is usually tolerable in
patients with moderately controlled diabetes, asthma and
obstructive lung disease.

47.  ARBs are non-inferior to ACEIs in terms of reducing
mortality and hospitalizations.
 The most important factor in determining the extent of
reduction in mortality and thus the prognosis is the possibility
of achieving optimal doses of these agents.
 A number of patients with advanced heart failure may not be
able to achieve optimal doses of neurohormonal inhibitors due
to either intolerance or clinical instability. Such individuals
represent a high-risk cohort with poor prognosis.
 Neurohormonal escape: Circulating levels of angiotensin II
return to pre-treatment levels in some patients on long-term
ACEI therapy. ARBs blunt this phenomenon by binding
competitively to the AT1 receptor.

48. Sequence of administration:
– Either agent can be started first. In the CIBIS III trial
comparing bisoprolol vs enalapril, outcomes did not vary when
either agent was initiated first.
– What does matter is that optimally titrated doses of both
ACEIs and beta blockers can be established in a timely manner.
– ARBs can be added if patients in intolerant to ACEIs or beta-
blockers, but simultaneous administration of ACEI, ARBs and
beta-blockers have shown worse outcomes. (Val-HeFT trial).
– ARBS can be added in patients intolerant to MRA if the patient
is already on maximally tolerated doses of ACEIs and beta-
blockers.

49. Class effect Dose Uptitration:
– ACEIs exert their
beneficial effects as a
class; however, the
beneficial effects of beta-
blockers are limited to
specific drugs only, which
are carvedilol, bisoprolol,
and metoprolol
succinate.
– More the dose is taken
towards the target dose;
more is the reduction in
mortality and
hospitalization. Up
titration should be done
at every 2 weeks if well
tolerated.

50. Drug class Generic drug Initiation (mg) Target dose
(mg)
ACEI Lisinopril 2.5-5 qd 20-35 qd
Enalapril 2.5 bid 10-20 bid
Captopril 6.25 tid 50 tid
Ramipril 2.5 qd 10 qd
ARBs Losartan 50 qd 150 qd
Valsartan 40 bid 160 bid
Candesartan 4-8 qd 32 qd
Beta blockers Metoprolol
succinate CR/XL
12.5-25 qd 200 qd
Carvedilol 3.125 bid 25-50 bid
Bisoprolol 1.25 qd 10 qd

51. Angiotensin Receptor-
Neprilysin Inhibitor (ARNI)
– ARB (valsartan) with an endopeptidase inhibitor
(sacubitril).
– PARADIGM-HF TRIAL done in 2014 with 8442 patients
showed 16.5% patients of HFrEF receiving Enalapril died
from cardiovascular causes whereas this figure was only
13.3% in the LCZ696 group (p value <0.001). LCZ696
reduced the risk of hospitalization for heart failure by 21%.
– The LCZ696 group had lower proportions of patients with
renal impairment, hyperkalemia, and cough than the
enalapril group.

52. – Sacubitril/valsartan is recommended as a replacement for
an ACE-I to further reduce the risk of HF hospitalization and
death in ambulatory patients with HFrEF who remain
symptomatic despite optimal treatment with an ACE-I, a
beta-blocker and an MRA, have elevated natriuretic
peptides and able to tolerate enalapril 10 mg b.i.d.
– Cut off level of natriuretic peptides for starting ARNIs :
Patient not hospitalized
within the last 12 months
BNP ≥150 pg/mL or
NT-proBNP ≥600 pg/mL
If HF hospitalization within
the last 12 months
BNP ≥100 pg/mL or NT-
proBNP ≥400 pg/mL

53. – ARNI should not be administered concomitantly with ACE
inhibitors or within 36 hours of the last dose of an ACE
inhibitor.
– ARNI should not be administered to patients with a history
of angioedema.
– Dose: 100 mg bid initially upto 200 mg bid.
– Ratio of sacubitril: valsartan = 97:103
– Cost in INDIA: Rs 35 per tablet of 100 mg.

54. Mineralocorticoid Receptor
Antagonist (MRA):
– Increased aldosterone production in patients of HFrEF is
associated with higher mortality due to sodium retention,
electrolyte imbalance, endothelial dysfunction and
myocardial fibrosis.
– Use of MRA is thus, associated with reduction in mortality
and hospitalizations in all stages of symptomatic class II to
IV HFrEF.
– Significant reduction in sudden cardiac death.
– Eplerenone is selective and Spironolactone is non-selective
mineralocorticoid receptor antagonist.

55. – Main concerns are hyperkalemia and worsening renal
function, thus KFT and serum K+ levels must be closely
monitored.
– Spironolactone or eplerenone are recommended in all
symptomatic patients (despite treatment with an ACEI
and a beta-blocker) and LVEF ≤35%.
Drug Initial dose Target dose
Eplerenone 25 qd 50 qd
spironolactone 12.5-25 qd 25-50 qd

56. IVABRADINE:
– This drug inhibits If current in the sinoatrial node.
– It does not have a negative ionotropic effect like
beta-blockers.
– It has shown beneficial effects on mortality and
hospitalizations in patients of HFrEF with a heart
rate > 70 beats/min. (SHIFT trial).
– Starting dose is 5 mg bid and target dose is 7.5
mg bid.

57. Recommendations on
Ivabradine:
– Should be considered to reduce the risk of
hospitalization or death in symptomatic patients with
LVEF ≤35%, in sinus rhythm and a resting heart rate ≥70
bpm despite treatment with an evidence-based dose of
beta-blocker (or maximum tolerated dose below that),
ACE-I, and an MRA.
– Should be considered to reduce the risk of
hospitalization and death in symptomatic patients with
LVEF ≤35%, in sinus rhythm and a resting heart rate ≥70
bpm who are unable to tolerate or have contra-
indications for a beta-blocker. Patients should also
receive an ACE-I and an MRA.

58. Role of arteriovenous
vasodilators in HFrEF:
– A-Heft trial done in self identified African Americans studied a
fixed dose of isosorbide dinitrate with hydralazine in patients
with advanced symptoms of HFrEF who were receiving
standard background therapy. The study demonstrated
reduction in mortality and hospitalizations rates in the
treatment group, although less than that caused by ACEIs or
ARBs.
– Hydralazine and isosorbide dinitrate should be considered in
self-identified black patients with EF ≤35% or with an LVEF
<45% combined with a dilated LV in NYHA Class III–IV despite
treatment with an ACE-I a beta-blocker and an MRA.

59. – Hydralazine and isosorbide dinitrate may be considered in
symptomatic patients with HFrEF in which RAAS based
therapy is either intolerable or contraindicated.
– Initial dose of Hydralazine Isosorbide dinitrate: 37.5/20 mg
tid , target dose : 75/40 mg tid
– Limitation : thrice daily dosing

60. Digoxin:
– It exerts mild inotropic effect and is sympatho-inhibitory. (It
decreases serum norepinephrine levels, plasma renin
levels, possibly aldosterone levels.)
– May be considered in symptomatic patients in sinus rhythm
despite treatment with an ACE-I, a beta-blocker and an
MRA, to reduce the risk of hospitalization.
– No reduction in mortality or improvement in QOL is seen
with the use of this drug (DIG trial). Rather, increased
mortality and hospitalizations was seen in women.

61. – Caution should be exerted in females, in the elderly and in
patients with reduced renal function.
– Low doses are sufficient to achieve any potentially
beneficial outcomes.
– In patients with symptomatic HF and AF, digoxin may be
useful to slow a rapid ventricular rate, but it is only
recommended for the treatment of patients with HFrEF
and AF with rapid ventricular rate when other therapeutic
options cannot be pursued.

62. CARDIAC
RESYNCHRONIZATION
THERAPY (CRT)

63. Types of CRT devices:
– Cardiac resynchronization therapy with a pacemaker
(CRT-P).
– Cardiac resynchronization therapy with a pacemaker and
an ICD (CRT-D). People with heart failure who also have a
risk of sudden cardiac death may benefit from an ICD that
can detect arrhythmias.

64. Recommendations for CRT
implantation in patients with
heart failure:
– CRT is recommended for symptomatic patients with HF in
sinus rhythm with a QRS duration ≥130 msec and LBBB QRS
morphology and with LVEF ≤35% despite OMT in order to
improve symptoms and reduce morbidity and mortality.
– CRT should be considered for symptomatic patients with HF in
sinus rhythm with a QRS duration ≥150 msec and non-LBBB
QRS morphology and with LVEF ≤35% despite OMT in order to
improve symptoms and reduce morbidity and mortality.
– CRT is contra-indicated in patients with a QRS duration < 130
msec.

65. IMPLANTABLE
CARDIOVERTER-
DEFIBRILLATOR
(ICD)

66. Recommendations for implantable
cardioverter-defibrillator (ICD):
1. Secondary prevention
An ICD is recommended to reduce the risk of sudden death and all-cause
mortality in patients who have recovered from a ventricular arrhythmia
causing haemodynamic instability, and who are expected to survive for >1
year with good functional status.
2. Primary prevention
An ICD is recommended to reduce the risk of sudden death and all-cause
mortality in patients with symptomatic HF (NYHA Class II–III), and an
LVEF ≤35% despite ≥3 months of OMT, provided they are expected to
survive substantially longer than one year with good functional status, and
they have:
o IHD (unless they have had an MI in the prior 40 days).
o DCMP

67. – ICD implantation is not recommended within 40 days of an
MI, as implantation at this time does not improve
prognosis.
– ICD therapy is not recommended in patients in NYHA Class
IV with severe symptoms refractory to pharmacological
therapy.
– A wearable ICD may be considered for patients with HF
who are at risk of sudden cardiac death for a limited period
or as a bridge to an implanted device.

68. Therapeutic algorithm
for a patient with
symptomatic heart
failure with reduced
ejection fraction:

69. Other potentially effective
therapies in HFrEF:
– Fish oil (PUFA) - GISSI-HF trial
– Iron supplementation
– Thiamine and Selenium supplementation (in those with
deficiency)
– ECCP (Enhanced external counter pulsation)
– Exercise training

70. Treatments not recommended
(unproven benefit) in
symptomatic patients of HFrEF
– Statins
– Oral anticoagulants and antiplatelet therapy
– Renin inhibitors (ASTRONAUT trial)
– EPO for anaemia
– SSRI for depression

71. Following drugs are associated
with non-favourable outcome in
HFrEF
– Bosenten (endothelin antagonist)
– Moxonidine (centrally acting sympatholytic agent)
– Omapatrilat (ACEI+ endopeptidase inhibitor) – OVERTURE
trial
– Xamoterol (beta blocker with intrinsic sympathomimetic
activity)

72. Treatments (or combinations of
treatments) that may cause
harm in patients with HFrEF
– Non-dihydropyridine calcium-channel blockers e.g.
Diltiazem and verapamil. (There is only evidence on safety
for amlodipine and felodipine in patients with HFrEF, and
they can be used only if there is a compelling indication in
patients with HFrEF.)
– NSAIDs or COX-2 inhibitors
– Thiazolidinediones (glitazones).

73. MANAGEMENT OF
CO MORBIDITIES
ASSOCIATED WITH
HEART FAILURE:-

74. Sleep disordered breathing :
– Includes obstructive sleep apnea, central sleep apnea and
extreme form Cheyne-Stokes breathing.
– Central sleep apnoea (CSA) has been identified as an
independent predictor of increased morbidity and
mortality in patients with heart failure.
– Mechanism: Frequent hypoxic episodes and arousals ►
Adrenergic surge ►Worsening of hypertension ►
Impairment of systolic and diastolic function ► Worsening
of heart failure.

75. – Suspect sleep disordered breathing in those patients of HF
who present with
– Difficult to control hypertension
– Predominant symptoms of fatigue despite reverse
remodelling in response to optimal medical therapy.
– Worsening of right heart function with improvement in left
ventricular function. (pulmonary hypertension and occult
pulmonary embolism should be ruled out).

76. – Treatment : Nocturnal positive airway pressure
– No mortality benefit seen with Adaptive servo ventilation
(SERVE-HF trial). It is a positive airway pressure ventilatory
support that is adjusted based on the detection of apnea,
or pauses in breathing, during sleep.

77. Anemia
– Common comorbidity in heart failure, accountable for
worsening in functional status.
– More common in elderly, in those with advanced HF, in
presence of renal insufficiency, and in women.
– Iron deficiency, dysregulation of Iron metabolism are the main
mechanisms.
– IV Iron supplementation using either iron sucrose or
carboxymaltose is the recommended therapy which improves
functional status.(FAIR-HF and CONFIRM-HF trials)
– Oral Iron or Erythropoiesis stimulating agents: Not useful.

78. Atrial fibrillation:
– Urgent electrical cardioversion for hemodynamically
unstable cases if AF is thought to be contributing to the
patient’s haemodynamic compromise.
– For patients in NYHA Class I–III, a beta-blocker, usually
given orally, is safe and therefore is recommended as a first
line treatment to control ventricular rate, provided the
patient is euvolaemic. If the rate does not improve on beta
blockers or beta-blocker is contraindicated /intolerated,
then the next drug in line is digoxin.

79. – For patients in NYHA Class IV, in addition to treatment for
HF, an intravenous bolus of amiodarone or, in digoxin-naïve
patients, an intravenous bolus of digoxin should be
considered to reduce the ventricular rate.
– Rhythm control may be considered in patients with
persisting symptoms and/or signs of HF, despite OMT and
adequate control of ventricular rate, to improve
clinical/symptomatic status.
– Amiodarone and Dofetilide are found to be safe and
effective in this regard.

80. Diabetes mellitus:
– SGLT-2 inhibitors like Empagliflozin have shown significant
reduction in cardiovascular mortality as well as
hospitalizations for heart failure.
– Metformin, sulfonylureas(2nd gen.), insulin, GLP-1
analogues : Neutral
– DPP-4 inhibitors like saxagliptin , alogliptin : potential risk
– Thiazolidinedoines : Harm