2. DEFINITION
• Heart failure is “a complex clinical syndrome that can result from any
structural or functional cardiac disorder that impairs the ability of the
ventricle to fill with or eject blood.” (AHA/ACC)
• Heart failure can be defined as an abnormality of cardiac structure or
function leading to failure of the heart to deliver oxygen at a rate
commensurate with the requirements of the metabolizing tissues
(despite normal filling pressures or only at the expense of increased
filling pressures).
American HeartAssociation (AHA) and theAmerican College of Cardiology
(ACC),
3. EPIDEMIOLOGY
More than 20 million people affected worldwide
Overall prevalence of HF in developed countries - 2 %
Affects 6-10 % of people aged >65%
60-70% of heart failure patients die within 5 years from diagnosis
Broadly categorized into
1. HF with a reduced EF (HFrEF)
2. HF with a preserved EF (HFpEF)
3. HF with a borderline or mid-range EF (LVEF between 40%-50%)
4. INTRODUCTION
• Heart failure accounts for 5% of admissions to hospital medical wards.
• Mean length of hospital stay increases with each rehospitalisation for HF
• HF severity can be classified based on structure and damage to heart
(ACC/AHA) or based on symptoms or physical activity (NYHA).
• There are many causes of HF that result in ventricular remodelling, reduction of
the left ventricular ejection fraction, and neurohumoral imbalance.
• The prognosis of heart failure has improved recent years, but the mortality rate
is still high with approximately 50% of patients dead at 5 years.
7. DESCRIPTIVE TERMS
• Related to Ejection Fraction: HFrEF, HFmEF, HFpEF
• Related to time-course:
• Related to progression:
• Related to location:
New onset, transient,chronic
Acute, stable, Worsening/decompensating
Left heart, right heart,combined/congestive
• Half of patients with heart failure will have preserved EF.
8. THE ACC/AHA STAGES OF HEARTFAILURE
(BASED ON STRUCTURE & DAMAGETOTHE
HEART)
ACC/AHA Stage Symptoms
A At high risk for heart failure but without structural heart disease or
symptoms of heart failure.
B (Development of) Structural heart disease but without signs or
symptoms of heart failure.
C Structural heart disease with prior or current symptoms of heart
failure. (i.e. Symptomatic HF with underlying structural heart disease)
D Refractory heart failure requiring specialized interventions. (Advanced
structural disease. Marked symptoms of HF at rest despite maximal
medical therapy)
9. NYHA FUNCTIONAL CLASSIFICATION
NYHA Class
Class I No limitation of physical activity.
Ordinary physical activity does not cause undue fatigue,
palpitation,dyspnoea or anginal pain.
Class II Slight limitation of physical activity. Comfortable at rest.
Ordinary physical activity results in fatigue, palpitation,
dyspnoea or anginal pain.
Class III Marked limitation of physical activity. Comfortable at rest.
Less than ordinary activity causes fatigue, palpitation,or
dyspnoea or anginal pain.
Class IV Inability to carry on any physical activity without discomfort.
Symptoms of heart failure or anginal syndrome even at rest.
If any physical activity is undertaken, discomfort increases.
10. Pathogenesis of HF with reduced EF
Heart failure begins after an index event
an initial decline in the heart’s pumping capacity
variety of compensatory mechanisms are activated
(adrenergic nervous system, RAAS, cytokine system)
In the short term, these systems able to restore cardiovascular function and patient asymptomatic
sustained activation of these systems leads to secondary end-organ damage within the ventricle,
worsening left ventricular remodelling and subsequent cardiac decompensation
11. Pathogenesis of HF with preserved EF
• Pathogenis still not fully understand, evolving
• Diastolic dysfunction- main factor
• Extracardiac mechanisms - ineased vascular stiffnes, impaired renal function.
Reduction in ATP concentration, as occurs in ischemia, may cause slowed myocardial relaxation.
Alternatively, if LV filling is delayed because LV compliance is reduced (e.g., from hypertrophy or
fibrosis), LV filling pressures will remain elevated at end diastole.
An increase in heart rate disproportionately shortens the time for diastolic filling, which may lead to
elevated LV filling pressures, particularly in noncompliant ventricles.
Elevated LV end diastolic filling pressures result in increases in pulmonary capillary pressures,
which can contribute to the dyspnoea experienced by patients with diastolic dysfunction.
In addition to impaired myocardial relaxation, increased myocardial stiffness secondary to cardiac
hypertrophy and increased myocardial collagen content may contribute to diastolic failure.
13. The decreased cardiac output in HF patients results in an “unloading” of high-pressure baroreceptors in
the left ventricle, carotid sinus, and aortic arch
This unloading of the peripheral baroreceptors leads to a loss of inhibitory parasympathetic tone to the
central nervous system with a resultant generalized increase in efferent sympathetic tone, and non-
osmotic release of ADH from the pituitary.
Antidiuretic hormone [ADH]) is a powerful vasoconstrictor that increases the permeability of the renal
collecting ducts, leading to the reabsorption of free water.
These afferent signals to the CNS also activate efferent sympathetic nervous system pathways that
innervate the heart, kidney, peripheral vasculature, and skeletal muscles.
Sympathetic stimulation of the kidney leads to the release of renin, with a resultant increase in the
circulating levels of angiotensin II and aldosterone.
The activation of the renin-angiotensin-aldosterone system promotes salt and water retention and leads
to vasoconstriction of the peripheral vasculature, myocyte hypertrophy, myocyte cell death, and
myocardial fibrosis.
Although these neurohormonal mechanisms facilitate short term adaptation by maintaining blood
pressure, these same neurohormonal mechanisms result in end-organ changes in the heart and the
circulation, as well as to the excessive salt and water retention in advanced HF.
14. LEFT VENTRICULAR REMODELLING
• Ventricular remodelling refers to the changes in LV mass, volume, and shape and the composition of the
heart that occur after cardiac injury and/or abnormal hemodynamic loading conditions.
• In addition to the increase in LV end-diastolic volume, LV wall thinning occurs as the left ventricle begins
to dilate. The increase in wall thinning, along with the increase in afterload created by LV dilation, leads
to a functional afterload mismatch that may contribute further to a decrease in stroke volume.
• Moreover, the high end-diastolic wall stress might be expected to lead to
(1) hypoperfusion of the sub-endocardium, with resultant worsening of LV function
(2) increased oxidative stress, with the resultant activation of families of genes that are sensitive to free
radical generation (e.g., TNF and interleukin 1β)
(3) sustained expression of stretch activation of hypertrophic signalling pathways.
• Increasing LV dilation also results in tethering of the papillary muscles with resulting incompetence of the
mitral valve apparatus and functional mitral regurgitation, which in turn leads to further hemodynamic
overloading of the ventricle.
• Taken together, the mechanical burdens that are engendered by LV remodelling contribute to the
progression of HF.
15.
16. SYMPTOMS OF HEART FAILURE
• SYMPTOMS:Typical
• Breathlessness/Dyspnoea
• Orthopnoea
• Paroxysmal nocturnal dyspnoea
• Cheyne-Stokes respiration
• Reduces exercise tolerance
• Fatigue, tiredness and increased
time to recover after exercise
• Ankle swelling/ fluid retention
• Nonspecific symptoms
• chronic non-productive cough
• norexia, nausea, early satiety
• Confusion, disorientation
• Sleep and mood disturbances
• Right ventricular failure :
• Right upper quadrant pain 20 to
hepatic congestion
• Peripheral oedema.
17. Dyspnoea: Pulmonary congestion with accumulation of interstitial or intra-alveolar fluid which
activates juxta-capillary J receptors, which in turn stimulate the rapid, shallow breathing characteristic
of cardiac dyspnoea. Other factors that contribute to dyspnoea on exertion include reductions in
pulmonary compliance, increased airway resistance, respiratory muscle and/or diaphragm fatigue,
and anaemia.
Orthopnoea: It results from redistribution of fluid from the splanchnic circulation and lower
extremities into the central circulation during recumbency, with a resultant increase in pulmonary
capillary pressure. Nocturnal cough is a common manifestation of this process.
Paroxysmal Nocturnal Dyspnoea: Acute episodes of severe shortness of breath and
coughing that generally occur at night and awaken the patient from sleep, usually 2–3 h after the
patient retires. PND may manifest as coughing or wheezing, possibly because of increased pressure
in the bronchial arteries leading to airway compression, along with interstitial pulmonary enema that
leads to increased airway resistance.
CHEYNE-STOKES RESPIRATION: eriodic respiration / cyclic respiration. Cheyne-
Stokes respiration is caused by an increased sensitivity of the respiratory centre to arterial Pco2.
There is an apnoeic phase, during which arterial Po2 falls and arterial Pco2 rises. These changes in
the arterial blood gas content stimulate the respiratory centre, resulting in hyperventilation and
hypocapnia, followed by recurrence of apnoea.
18. SIGNS OF HEART FAILURE
SIGNS:
• Elevated jugular venous pressure
• Peripheral edema
• Pulmonary crackles (due to transudation of fluid from the intravascular space into the alveoli)
• Cardiac wheeze
• Third heart sound (gallop rhythm) - severe hemodynamic compromise, volume overload
• Laterally displaced apex beat - Cardiomegaly
• Cardiac murmur - commonly MR,TR
• Enlarged tender Liver, Ascites
• Hepatojugular reflux
19. DIAGNOSIS OF HEART FAILURE
Routine: CBC, S.Electrolytes, BUN, S.Creatine, Hepatic enzymes, Urine Routine
Cardiac Enzymes: Troponin T, CPK-MB, NT-Pro BNP
ECG: LVH, MI, QRS width. Normal ECG virtually excludes LV systolic dysfunction
CXR: Pulmonary edema, Pulmonary hypertension, interstitial edema.
2-D ECHO: LV size, function, RWMA, valvular status. RV size, pulmonary pressure - cor pulmonale.
The presence of left atrial dilation and LV hypertrophy, together with abnormalities of LV
diastolic filling is useful for the assessment of HF with a preserved EF.
MRI: comprehensive analysis of cardiac anatomy and function - now gold standard for assessing LV
mass and volumes (esp. in amyloidosis, ischemic cardiomyopathy, hemochromatosis etc.)
Myocardial strain rate imaging using speckle tracking: standard measurement of
LV EF.
20. BIOMARKERS
• Trop T and CPK-MB
• Circulating levels of natriuretic peptides like B-type natriuretic peptide (BNP) and N-terminal pro-
BNP (NT-proBNP), which are released from the failing heart, are relatively sensitive markers for
the presence of HF with depressed EF; they also are elevated in HF patients with a preserved EF.
• The measurement of BNP or NT-proBNP is useful for establishing prognosis or disease severity in
chronic HF and can be useful to achieve optimal dosing of medical therapy.
• Natriuretic peptide levels increase with age and renal impairment, more elevated in women. BNP
levels may increase in patients taking ARNIs. Levels can be falsely low in obese patients.
• Soluble ST-2 and galectin-3, are newer biomarkers that can be used for determining the prognosis
of HF patients.
• A peak oxygen uptake (vo2) <14 mL/kg per min (Treadmill test) is associated with a
relatively poor prognosis.
23. COR PULMONALE
(PULMONARY HEART DISEASE)
• Altered RV structure and/or function in the context of
chronic lung disease and is triggered by the
presence of pulmonary hypertension.
24. PATHOPHYSIOLOGY
In parenchymal lung diseases, primary pulmonary vascular disorders, or chronic hypoxia
Circulatory bed undergoes vascular remodelling, vasoconstriction, and destruction.
Pulmonary artery pressures and RV afterload increases - cor pulmonale
Alterations in cardiac output as well as salt and water homeostasis
The sustained pressure overload eventually leads to RV dysfunction and failure.
25. CLASSIFICATION
Acute cor pulmonale: Occurs after a sudden and severe stimulus (e.g., massive pulmonary
embolus), with RV dilatation and failure but no RV hypertrophy
Chronic cor pulmonale: evolves slowly with modest compensatory RV hypertrophy that
lowers wall tension and preserves RV function. Over time, RV dilation ensues leading to an
increase in RV wall tension and overt dysfunction
Acute decompensation of compensated chronic cor pumonale: Triggers
include worsening hypoxia from any cause (e.g., pneumonia), acidaemia (e.g., exacerbation of
COPD), acute pulmonary embolus, atrial tachyarrhythmia, hypervolemia, and mechanical
ventilation that compresses blood vessels associated with alveoli and further increasing RV
afterload.
26. SYMPTOMS
• Dyspnoea
• Peripheral edema, ascites
SIGNS
• Elevated jugular venous pressures with prominent v waves indicative of tricuspid regurgitation
• Hepatomegaly, pulsatile liver, ascites
• Lower-extremity edema.
• Cyanosis is a late finding in cor pulmonale and is secondary to a low cardiac output, systemic
vasoconstriction and hypoxemia.
27. DIAGNOSIS
ECG: P pulmonale, right axis deviation, and RV hypertrophy.
CXR: Enlargement of the main central pulmonary arteries and hilar vessels.
PFT: Obstructive and/or restrictive defects indicative of parenchymal lung diseases.
ABG: Hypoxemia with or without hypercapnia.
HRCT Chest: Interstitial lung disease and the extent of emphysema.
Chest CT angiogram: Acute pulmonary emboli.
Ventilation-perfusion scan: Chronic thromboembolic disease.
28. 2-D ECHO: RV wall thickness and chamber dimensions. The interventricular septum may move
paradoxically during systole in the presence of RV pressure overload, highlighting a deleterious
interaction between the RV and the LV.
Doppler echocardiography can be used to assess pulmonary artery pressures.
MRI: Assessing RV structure and function.
Cardiac catheterization: Diagnosis of pulmonary hypertension.
BNP and N-terminal BNP levels: Elevated in patients with cor pulmonale secondary to RV
myocardial stretch.
30. • Diet and life style modifications.
• Avoidance or reversal of obesity.
• Moderate regular exercise.
• Adherence to medications.
• Weight monitoring.
• Close medical follow up.
• Sodium restriction to less than 2 g/day
• Fluid intake should be balanced to maintain adequate renal
function (preventing hypotension and renal hypoperfusion)
NON- PHARMACOLOGICAL MANAGMENT
32. Outline
Has poor prognosis compared to HFrEF. Main goal is:
– Toreduce pulmonary and peripheral venous congestion.
– Toreduce heart rate and blood pressure.
– Toimprove exercise tolerance.
– Totreat the cause and precipitating factors for HF like hypertension, coronary artery disease,
diabetes, obstructive sleep apnea, anemia and maintain adequate renal function.
– Weight loss in obese patients either through diet or bariatric surgery improves diastolic function
indices.
33. Pharmacological management and evidence from
Random Clinical Trials
None of the other pharmacological agents are effective in HFpEF compared to HFrEF.
• Digitalis: Did not reduce the end point mortality. So of not much use in HFpEF.
(Digitalis Intervention Group – DIG trial.)
• ARB – Candesartan: Fewer patient on ARB Candersartan showed reduced number of
hospitalizations in patient with HFpEF but did not reduce the mortality rate compared to placebo.
(Candesartan in Heart Failure - Assessment of Mortality and Morbidity – CHARM trial.)
• ARB – Irbesartan: Did not show any differences in the end point of hopitalizations compared to
placebo. (Irbesartan in Heart Failure with preserved ejection fraction – I-PRESERVE trial.)
• Empgagliflozin (SGLT-2 Inhibitor): Empagliflozin reduced the combined risk of
cardiovascular death or hospitalization for heart failure in patients with heart failure
and a preserved ejection fraction, regardless of the presence or absence of diabetes.
(EMPEROR-Preserved trial)
34. • Nebivolol: β1 antagonist with vasodilator properties did not show any benefit in mortality. (The
Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with
Heart Failure (SENIORS) trial)
• Sildenafil: PDE-5 inhibitor did not show any improvement in functional capacity, quality of life.
(RELAX trial.)
• Spironolactone: Showed benefit in number of hospitalization in patients with HFpEF but did not
show any advantage with end stage. (TOPACT and ALDO-DHF trials.)
• Sacubitril/valsartan: Sacubitril–valsartan did not result in a significantly lower rate of total
hospitalizations for heart failure and death from cardiovascular causes among patients with heart
failure and an ejection fraction of 45% or higher( PARAGON-HF ClinicalTrials).
• Isosorbide mononitrate: did not improve QOL or submaximal exercise capacity, and decreased
overall activity levels in treated patients [Nitrate’s Effect on Activity Tolerancein Heart Failure with
Preserved Ejection Fraction (NEAT-HFpEF)].
36. Pharmacological Management
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Management of fluid retention
– Loop diuretics.
– Thiazide and thiazide like diuretics.
– Potassium sparing diuretics.
Prevention of disease progression
– ACE inhibitors.
– Angiotensin receptor blockers.
– Beta blockers.
– Aldosterone antagonists.
– Other agents – (Hydralzine/isosorbide dinitrate), Digoxin, Ivabradine.
37. Loop Diuretics
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Include drugs like furosemide, bumetanide, torsemide act by reversibly inhibiting the
Na+K+2Cl- symporter (cotransporter) on the apical membrane of epithelial cells in the thick
ascending loop of Henle.
The bioavailability of furosemide ranges from 40% to 70% of the oral dose. By contrast,
the oral bioavailability of bumetanide and torsemide exceeds 80%.
Ethacrynic acid is another class of loop diuretics which shows only slower, delayed and
partial reversibility of action. May be safely used in patients with sulfa allergy.
These drugs are required in almost all patients with heart failure.
These drugs relieve the symptoms and signs of heart failure most rapidly and
effectively than any other class of drugs.
38. Thiazide and thiazide like diuretics
• Thiazide diuretics, like Chlorthiazide, Chlorthalidone, Hydrochlorthiazide were the initial
class of drugs that were synthesized to block the Na+Cl- transporter in the cortical portion
of the ascending loop of Henle and the distal convoluted tubule.
• Thiazide like diuretics Metolazone is used in combination with furosemide in
patients who become resistant to diuretics.
• Compared to loop diuretics have a gentler but long lasting diuretic effect.
• Combination with loop diuretics can cause severe hyponatremia, and prerenal azotemia.
• These drugs increase Ca2+ resorption and decrease Mg2+ resorption leading to
hypercalcemia and hypomagnesemia respectively.
39. Potassium sparing diuretics
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Include Triamterene andAmiloride.
Share common property of mild increase in NaCl excretion and antikaluritic
properties.
Alone not useful in achieving net negative Na+ balance.
40. ACE Inhibitors
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ACE inhibitors interfere with the renin-angiotensin system by inhibiting the enzyme that is
responsible for the conversion of angiotensin I to angiotensin II.
ACE inhibitors also inhibit kininase II, they may induce the upregulation of bradykinin, which
may further enhance the effects of effects of angiotensin suppression.
ACE inhibitors stabilize LV remodeling, relieve patient symptoms, prevent hospitalization, and
prolong life.
Concomitant diuretic use may precipitate hypotension.
Should be started at low dose and titrated doubling the dose every 3 to 5 days.
Decreases in blood pressure with mild azotemia may be common during initiation of therapy.
41. • Blood pressure (including postural changes), renal function, and potassium should be
evaluated within 1 to 2 weeks after initiation of ACE inhibitors, especially in patients with
preexisting azotemia, hypotension, hyponatremia, diabetes mellitus, or in those taking
potassium supplements.
• Abrupt withdrawal of treatment with an ACE inhibitor may lead to clinical deterioration and
should therefore be avoided in the absence of life-threatening complications (e.g.,
angioedema, hyperkalemia).
• Potassium retention especially in those receiving potassium supplements /
potassium sparing diuretics.
• Side effects related to kinin potentiation include dry cough and angioedema. In these
patients ARBs can be used.
42. Angiotensin Receptor Blockers
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Lack the side effects of cough, skin rash and angioedema and can be used in all
patients who are ACE-I intolerant.
Have same adverse effects of hyperkalemia and renal insufficiency as
ACE-I.
No benefit of combining ARB withACE-I.
Should be initiated at low doses and uptitrated every 3-5 days.
Blood pressure, renal function and potassium levels should be reassessed within
a week after initiation of treatment.
ACE-I remain the first line of choice in HF in those tolerant to ACE-I compared
to ARB.
43. Angiotensin Receptor-Neprilysin Inhibitors (ARNi)
• Marketed as Vymada, Entresto is a 1:1 combination of sacubitril and valsartan.
• Combination is an angiotensin receptor-neprilysin inhibitor (ARNi). Valsartan blocks AT-2 receptor
and sacubitril a prodrug activated to sacubitrilat by esterases inhibits the enzyme neprilysin, a
neutral endopeptidase that degrades vasoactive peptides, including natriuretic peptides,
bradykinin, and adrenomedullin. Thus, sacubitril increases the levels of these peptides, causing
blood vessel dilation and reduction of ECF volume via sodium excretion.
• In the large, randomized, double-blind, PARADIGM-HF trial, sacubitril/valsartan reduced the
incidence of death from cardiovascular causes or first hospitalization for worsening heart failure
significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril.
• Approved in the US and the EU for the treatment of chronic heart failure (NYHA class II-IV) with
reduced ejection fraction (HfrEF).
• Adverse effects similar to ARBs and has a more risk of symptomatic hypotension compared
to ACE-I/ARB used alone.
44. β-blockers
• Interfere with harmful effects of sustained sympathetic activation by blocking α1, β1
and β2 receptors.
• When given in concert with ACE inhibitors, beta blockers reverse the process of LV
remodeling, ameliorate patient symptoms, prevent hospitalization, and prolong life.
• The β blockers that have been shown to reduce risk of death in patients with HF include
bisoporlol, sustained release metoprolol succinate (both block β1 receptor) and
carvedilol (which blocks α1, β1 and β2 receptors.)
• The dose of beta blocker should be increased until it approximates doses that have
been reported to be effective in clinical trials.
45. • Unlike with ACE inhibitors, which may be uptitrated relatively rapidly, the dose titration of beta
blockers should proceed no sooner than 2-week intervals.
• Initiation and/or increased dosing of these agents may lead to worsening fluid retention consequent
to the abrupt withdrawal of adrenergic support to the heart and the circulation.
• Nebivolol is a selective β1 receptor antagonist with ancillary vasodilatory properties that are
mediated, at least in part, by nitricoxide.
• Side effects include fatigue and weakness, which usually subsides within weeks to months after
initiation of therapy.
• Exacerbates bradycardia and heart blocks. Dose reduction required if Heart rate falls <50/min or if
2nd or 3rd degree block develops of patient has symptomatic hypotension.
46. Aldosterone antagonists
• Excessive aldosterone promotes Na+ retention and K+ loss, believed to cause myocaridal
fibrosis and predisposition to arrhythmias.
• Include Spironolactone and Eplerenone.
• Recommended for use in patients with NYHA classes II to IV and with EF < 35% and are
receiving standard treatment with diuretics, ACE-I/ARB and β blockers.
• Dose should be increased to the dose proven effective in clinical trials for maximum
benefit.
• Not recommended in patients with creatinine > 2.5 mg/dL or those with potassium
levels > 5.5 mmol/liter.
47. ●
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Potassium supplements to be stopped prior to initiation of therapy and patients
should be advised to avoid potassium rich diets.
Potassium levels to be rechecked within 3 days, a week later and subsequent
monitoring of renal function and fluid status monthly for 6 months.
Spironolactone has an antiandrogenic effect and can cause painful
gynecomastia seen in 10-15 % patients in whom eplerenone which has less of
an effect compared to spironolactone may be substituted.
48. Ivabradine
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Ivabradine is a heart rate–lowering agent that acts by selectively blocking the cardiac pacemaker If
(“funny”) current that controls the spontaneous diastolic depolarization of the sinoatrial node.
Ivabradine blocks If channels in a concentration-dependent manner by entering the channel
pore from the intracellular side and thus can only block the channel when it is open.
The magnitude of If inhibition is directly related to the frequency of channel opening and would
therefore be expected to be most effective at higher heart rates.
Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT) showed that
Ivabradine (uptitrated to a maximal dosage of 7.5 mg twice daily) reduced the primary composite
outcome of cardiovascular death and HF hospitalization by 18%.
49. Renin inhibitors
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Aliskiren, a orally active direct renin inhibitor that appears to suppress renin angiotensin
system similar to ACE-I.
Aliskiren is a nonpeptide inhibitor that binds to the active site (S1/S3 hydrophobic
binding pocket) of renin, preventing the conversion of angiotensinogen to
angiotensin I.
Benefits of ACE-I / ARB are limited by compensatory increase in renin levels and may attenuate
the effects. ‘RAAS escape’ where as Aliskiren can be useful.
ALOFT and ASTRONAUT trials showed reduction of natriuretic peptide levels in patients with
HFrEF but ASTRONAUT trial showed no significant difference in hospitalization or mortality. Also
rates of hyperkalemia, hypotension and renal impairment/failure are more in Aliskerin group.
ATMOSPHERE, a phase III study is currently in progress to assess Aliskiren monotherapy
and combination therapy with enalapril.
50. Digoxin
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Exerts a mild inotropic effect, attenuate carotid sinus baroreceptor activity, and are
sympathoinhibitory. These effects decrease serum norepinephrine levels, plasma renin levels,
and possibly aldosterone levels.
The DIG trial demonstrated a reduction in heart failure hospitalizations in the treatment
group but no reduction in mortality or improvement in quality of life.
Therapy with digoxin commonly is initiated and maintained at a dose of 0.125 to 0.25 mg daily.
Serum digoxin level should be below 1.0 ng/mL, especially in elderly patients, patients with
impaired renal function, and patients with a low (lean) body mass.
Digoxin can cause anorexia, nausea, arrhythmias, confusion, and visual disturbances,
especially if the serum concentration is above 2.0 ng/mL. Hypokalemia increases
susceptibility to the adverse effects.
The concomitant use of quinidine, verapamil, spironolactone, flecainide, propafenone, and
amiodarone can increase serum digoxin levels and may increase the risk of adverse reactions
51. Hydralazine/Isosorbide dinitrate
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Hydralazine is a powerful direct-acting arterial vasodilator. Nitrates are transformed in
smooth muscle cells into nitric oxide, which stimulates cyclic guanosine monophosphate
production and consequent arterial-venous vasodilation.
Although this combination has been known for some time to improve systolic function
HFrEF and probably to reduce death in class II to IV heart failure compared with placebo. It
is inferior to ACE-I orARB.
The combination of hydralazine and isosorbide dinitrate is recommended in African American
patients with NYHA class III or IV symptoms and an ejection fraction of 45% or less despite
treatment with standard disease-modifying drugs, that is, an ACE inhibitor, β-blocker, and
mineralocorticoid receptor antagonist.
In individuals with HFrEF unable to tolerate renin-angiotensin-aldosterone based therapy
for reasons such as renal insufficiency or hyperkalemia, this combination is preferred as a
disease-modifying approach.
52. Implantable Cardioverter Defibrillators
• Most common cause of death in patients with HF is ventricular arrhythmias, especially in
patients with milder symptoms compared to patients in advanced heart failure where deaths
due to pump failure are common.
• ICD reduce the risk of death and improve survival in patients with class II and III HF and
systolic dysfunction.
• All patients with class II and III HF, irrespective of etiology and a left ventricular EF of <
35% despite treatment with disease modifying pharmacological therapy for > 3 months
should be considered for ICD.
• In patients with a terminal illness and a predicted life span of less than 6 months or in those
with NYHA class IV symptoms who are refractory to medications and who are not candidates
for transplant, the risks of multiple ICD shocks must be carefully weighed against the survival
benefits.
53. Cardiac Resynchronization Therapy (CRT)
• About 30% of patients with heart failure have substantial prolongation of the QRS duration
on the surface electrocardiogram, which is a marker of abnormal electrical activation of the
left ventricle causing dyssynchronous contraction, less efficient ventricular emptying, and,
often, mitral regurgitation.
• Atrioventricular coupling may also be abnormal, as reflected by a prolonged PR interval.
• Cardiac resynchronization therapy (CRT) with atrial-biventricular or multisite pacing optimizes
atrioventricular timing and improves synchronization of cardiac contraction.
• In symptomatic patients (NYHA class II to IV) who are in sinus rhythm have marked systolic
dysfunction (left ventricular ejection fraction ≤35%), and have a wide QRS, the addition of CRT
to optimal medical therapy and an ICD improves pump function, reduces mitral regurgitation,
relieves symptoms, and significantly prolongs exercise capacity.
• The greatest benefit appears to be in patients with a left bundle branch block (LBBB)
morphology and in patients with mild symptoms (NYHA class II).
54. HUMAN HEART TRANSPLANT
• Allogenic HHT is a therapeutic option for patients with refractory end-stage HF, who have
failed other options
• 5-year survival rate after HHt is 72.3% for males and 67.4% for females
• Despite success, heart transplant is limited by the number of hearts available.
