Heart Failure

Presented by : Dr. P. Veerakumar

 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).
 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%)
 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 F 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.
Etiology
 Types of Heart Failure

Acute Heart failure Chronic heart

failure
Mild to moderate HFrEF
HTN ADHF HFpEF
Acute pulmonary Edema HFmEF
Cardiogenic shock
 Acute Heart Failure
It is only 20 % of the time Denovo, 80 % it is Acute on chronic due to some
precipitating factor

Mild to moderate Non compliance

HTN ADHF Fluid issues
Acute pulmonary Edema Infectios
Cardiogenic shock Anemia
HTN
Thyroid disease
Myocardial ischemia
Atrial fibrillation
Stages of Heart Failure
NYHA Classification of Heart Failure
Pathogenesis of HF with Reduced EF
Pathogenesis of HF with Preserved
EF
Left Ventricular Remodeling
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 1ß)
(3) sustained expression of stretch activation of hypertrophic signaling 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.
 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
 Symptoms of Heart
Failure
SYMPTOMS :Typical Nonspecific symptoms
• Breathlessness/Dyspnoea • chronic non-productive cough
• Orthopnoea • norexia, nausea, early satiety
• Paroxysmal nocturnal • Confusion, disorientation
dyspnoea • Sleep and mood disturbances
• Cheyne-Stokes respiration Right ventricular failure :
• Reduces exercise tolerance • Right upper quadrant pain
• Fatigue, tiredness and secondary due to hepatic
increased time to recover after congestion
exercise • Peripheral oedema.
• Ankle swelling/ fluid retention
 Diagnosis of Heart Failure
Routine: CBC, S.Electrolytes, BUN, S.Creatine, Hepatic enzymes, Urine Routine
Cardiac Enzymes: NT-Pro BNP, Troponin T, CPK-MB,
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
 Bio markers

Trop T and CPK-MB

Circulating levels of natriuretic peptides like B-type natriuretic peptide (NP) 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 ANIs. 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.
CXR changes in Heart Failure
ECHO : Normal LV vs Dilated LV
Treatment
Non Pharmacological Management

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)
Heart Failure with Preserved Ejection
Freaction
HFpEF
 Outline

Has poor prognosis compared to HFrEF. Main goal is:

To reduce pulmonary and peripheral venous congestion.
To reduce heart rate and blood pressure.
To improve exercise tolerance.
To treat 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.
 Pharmacological management and
evidence from Random Clinical Trials
Trials
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)
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.)
 Pharmacological management and
evidence from Random Clinical Trials
Nebivolol: B, 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)].
Heart Failure with Reduced Ejection
Freaction
HFrEF
 Pharmacological Management

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 - (Hydrazine/isosorbide dinitrate), Digoxin, Ivabradine.
 Loop Diuretics

Include drugs like furosemide, bumetanide, torsemide act by reversibly

inhibiting the Na+K+2CI- 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.
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 Caz+ resorption and decrease Mgz+ resorption
leading to hypercalcemia and hypomagnesemia respectively.
 ACE Inhibitors

ACE inhibitors interfere with renin-angiotensin system by inhibiting the enzyme that is
responsible for the conversion of angiotensin I to angiotensin Il
ACE inhibitors also inhibit kininase Il, 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
Decreases in blood pressure with mild azotemia may be common during initiation of
therapy.
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).
Side effects related to kinin potentiation include dry cough and angioedema. In these
patients ARBs can be used.
Angiotensin Receptor Blockers

Lack the side effects of cough, skin rash and angioedema and can
be used in all patients who are ACE- intolerant.
Have same adverse effects of hyperkalemia and renal
insufficiency as ACE I.
No benefit of combining ARB with ACE-l.
ACE-I remain the first line of choice in HF in those tolerant to ACE-I
compared to ARB.
 Angiotensin Receptor - Neprilysin
Inhibitors
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.
PARADIGM-HE trial,
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 enal april.
Approved in the US and the EU for the treatment of chronic heart failure (NYHA class Il-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.
 ß-blockers

Interfere with harmful effects of sustained sympathetic activation by

blocking a1, ß1 and ß2 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 B blockers that have been shown to reduce risk of death in patients
with HF include bisoporlol, sustained release metoprolol succinate (both
block , receptor) and carvedilol (which blocks a1, ß1 and ß2 receptors.)
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.
 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 Il to IV and with EF < 35%
and are receiving standard treatment with diuretics, ACE-/ARB and ß blockers.
Not recommended in patients with creatinine > 2.5 mg/dL or those with
potassium levels > 5.5 mmol/liter.
Potassium supplements to be stopped prior to initiation of therapy and patients
should be advised to avoid potassium rich diets.
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.
 Ivabradine

lvabradine is a heart rate-lowering agent that acts by selectively blocking the

cardiac pacemaker I ("funny") current that controls the spontaneous diastolic
depolarization of the sinoatrial node.
Ivabradine blocks I, 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 I 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 I, 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%.
 Digoxin

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.
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
Hydralazine/lsosorbidedinitrate

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 Il to IV
heart failure compared with placebo. It is inferior to ACE-I or ARB.
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.
 Implantable Cardioverter
Defibrillator

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 I
and IlI HF and systolic dysfunction.
All patients with class Il 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.
 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 Il 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 ID
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).
 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.
Advice : Don't strain Ur Heart

Thank You