Heart failure

Dr. Vishvas
DEFINITION
• Heart failure (HF) is a clinical syndrome caused by the
inability of the heart to pump sufficient blood to meet the
metabolic needs of the body. HF can result from any disorder
that reduces ventricular filling (diastolic dysfunction) and/or
myocardial contractility (systolic dysfunction).
PATHOPHYSIOLOGY
• Causes of systolic dysfunction (decreased contractility) are reduction in muscle
mass (e.g., myocardial infarction [MI]), dilated cardiomyopathies, and ventricular
hypertrophy. Ventricular hypertrophy can be caused by pressure overload (e.g.,
systemic or pulmonary hypertension, aortic or pulmonic valve stenosis) or volume
overload (e.g., valvular regurgitation, shunts, high-output states).

• Causes of diastolic dysfunction (restriction in ventricular filling) are increased

ventricular stiffness, ventricular hypertrophy, infiltrative myocardial diseases,
myocardial ischemia and infarction, mitral or tricuspid valve stenosis, and
pericardial disease (e.g., pericarditis, pericardial tamponade).
• The leading causes of HF are coronary artery disease and hypertension.
• As cardiac function decreases after myocardial injury, the heart relies on the following compensatory
mechanisms: (1) tachycardia and increased contractility through sympathetic nervous system
activation; (2) the Frank-Starling mechanism, whereby increased preload increases stroke volume;
(3) vasoconstriction; and (4) ventricular hypertrophy and remodeling. Although these compensatory
mechanisms initially maintain cardiac function, they are responsible for the symptoms of HF and
contribute to disease progression.

• The neurohormonal model of HF recognizes that an initiating event (e.g., acute MI) leads to
decreased cardiac output but that the HF state then becomes a systemic disease whose progression is
mediated largely by neurohormones and autocrine/paracrine factors. These substances include
angiotensin II, norepinephrine, aldosterone, natriuretic peptides, arginine vasopressin,
proinflammatory cytokines (e.g., tumor necrosis factor
• a, interleukin-6 and interleukin-1 b), and endothelin-1.
• Common precipitating factors that may cause a previously compensated patient to
decompensate include noncompliance with diet or drug therapy, coronary
ischemia, inappropriate medication use, cardiac events (e.g., MI, atrial
fibrillation), pulmonary infections, and anemia.

• Drugs may precipitate or exacerbate HF because of their negative inotropic,

cardiotoxic, or sodium- and water-retaining properties.
CLINICAL PRESENTATION
• The patient presentation may range from asymptomatic to cardiogenic shock.
• The primary symptoms are dyspnea (particularly on exertion) and fatigue, which lead to exercise intolerance

• Other pulmonary symptoms include orthopnea, paroxysmal nocturnal dyspnea, tachypnea, and cough.
• Fluid overload can result in pulmonary congestion and peripheral edema.

• Nonspecific symptoms may include fatigue, nocturia, hemoptysis, abdominal pain, anorexia, nausea,
bloating, ascites, poor appetite, mental status changes, and weight gain.
• tachycardia, narrow pulse pressure, cardiomegaly, symptoms of pulmonary edema (extreme breathlessness,
anxiety, sometimes with coughing pink, frothy sputum), peripheral edema, jugular venous distention,
hepatojugular reflux, and hepatomegaly.
DIAGNOSIS
• A diagnosis of HF should be considered in patients exhibiting characteristic signs and symptoms.
• A complete history and physical examination with appropriate lab testing are essential in the initial evaluation
of patient suspected of having HF

• Lab tests for identifying disorder that may cause or worsen HF include CBC, serum electrolyte (ca and mg)
renal, hepatic and thyroid function test: urinalysis, lipid profile, HBA1c

• Ventricular hypertrophy can be demonstrated on chest x-ray or ECG. Chest x-ray may also show pleural
effusions or pulmonary edema.
• The echocardiogram is the single most useful evaluation procedure because it can identify abnormalities of
the pericardium, myocardium, or heart values and quantify the left ventricular ejection fraction (LVEF) to
determine if systolic or diastolic dysfunction is present
b-Blockers

• There is overwhelming clinical trial evidence that certain b-blockers slow disease progression, decrease
hospitalizations, and reduce mortality in patients with HF.

• Beneficial effects of b-blockers may result from antiarrhythmic effects, slowing or reversing ventricular
remodeling, decreasing myocyte death from catecholamine-induced necrosis or apoptosis (  A type of
neurohormone (a chemical that is made by nerve cells and used to send signals to other cells). Catecholamines are important in stress responses.
High levels cause high blood pressure which can lead to headaches, sweating, pounding of the heart, pain in the chest, and anxiety.) ,
preventing fetal gene expression, improving LV systolic function, decreasing heart rate and
• ventricular wall stress and thereby reducing myocardial oxygen demand, and inhibiting plasma renin release.

• The guideline recommend use of b-blockers in all stable patients with HF and a reduced LVEF in the
absence of contraindications or a clear history of b-blocker intolerance.
• Patients should receive a b- blocker even if symptoms are mild or well controlled with ACE inhibitor

• b-Blockers are also recommended for asymptomatic patients with a reduced LVEF (stage B) to decrease the
risk of progression to HF.
• Metoprolol CR/XL, carvedilol, and bisoprolol are the only b-blockers shown to reduce mortality in large HF
trials. It cannot be assumed that immediate-release metoprolol will provide benefits equivalent to metoprolol
CR/XL.
• Carvedilol, 3.125 mg twice daily initially; target dose, 25 mg twice daily (the target dose for patients
weighing more than 85 kg is 50 mg twice daily). Carvedilol CR should be considered in patients with
difficulty maintaining adherence to the immediate-release formulation.

• Metoprolol succinate CR/XL, 12.5 to 25 mg once daily initially; target dose, 200 mg once daily.

• Bisoprolol, 1.25 mg once daily initially; target dose, 10 mg once daily.

• Doses should be doubled no more often than every 2 weeks, as tolerated, until the target dose or the
maximally tolerated dose is reached
PHARMACOTHERAPY OF ACUTE
DECOMPENSATED HEART FAILURE

• Acute decompensated heart failure (ADHF) is a clinical syndrome of new or worsening signs and symptoms
of HF that often lead to hospitalization or an emergency department visit.

• IV loop diuretics, including furosemide, bumetanide, and torsemide, are used for acute decompensated HF,
with furosemide being the most widely studied and used agent.

• Bolus A single dose of a drug or other substance given over a short period of time.) diuretic administration decreases preload
by functional venodilation within 5 to 15 minutes and later (>20 min) via sodium and water excretion,
thereby improving pulmonary congestion. However, acute reductions in venous return may severely
compromise effective preload in patients with significant diastolic dysfunction or intravascular depletion.

• Because diuretics can cause excessive preload reduction, they must be used judiciously to obtain the desired
improvement in congestive symptoms while avoiding a reduction in cardiac output, symptomatic
hypotension, or worsening renal function.
• Diuresis may be improved by adding a second diuretic with a different mechanism of action blocker such as
metolazone or hydrochlorothiazide).

• The loop diuretic thiazide combination should generally be reserved for inpatients who can be monitored
closely for the development of severe sodium, potassium, and volume depletion.

• Very low doses of the thiazide-type diuretic should be used in the outpatient setting to avoid serious adverse
events
Positive Inotropic Agents

• Positive inotropes can help when your heart can't get enough blood to your body because it is too weak to pump
the amount of blood your body needs. Positive inotropes make your heart muscle contractions stronger, raising
your cardiac output to a normal level and increasing the amount of blood your heart can pump out.

• Dobutamine
• is a b1- and b2-receptor agonist with some a1-agonist effects. The net vascular effect is usually vasodilation.

• It has a potent inotropic effect without producing a significant change in heart rate. Initial doses of 2.5 to 5
mcg/kg/min can be increased progressively to 20 mcg/kg/min on the basis of clinical and hemodynamic
responses.

• Dobutamine increases cardiac index because of inotropic stimulation, arterial vasodilation, and a variable
increase in heart rate. It causes relatively little change in mean arterial pressure compared with the more
consistent increases observed with dopamine.
• Although concern over attenuation of dobutamine’s hemodynamic effects with prolonged administration has
been raised, some effect is likely retained.
• Consequently, the dobutamine dose should be tapered rather than abruptly discontinued.
Digoxin
• Although digoxin has positive inotropic effects, its benefits in HF are related to its neurohormonal effects.
Digoxin attenuates the excessive sympathetic
• nervous system activation present in HF patients, perhaps by reducing central sympathetic outflow and
improving impaired baroreceptor function. (Arterial baroreceptors function to inform the autonomic nervous system of beat-to-
beat changes in blood pressure within the arterial system.)

• It also increases parasympathetic activity in HF patients and decreases heart rate, thus enhancing diastolic
filling. Digoxin does not improve survival in patients with HF but does provide symptomatic benefits.

• In patients with HF and supraventricular tachyarrhythmias such as atrial fibrillation, digoxin should be
considered early in therapy to help control ventricular response rate.
• For patients in normal sinus rhythm, effects on symptom reduction and quality-of-life improvement are
evident in patients with mild to severe HF.
• Therefore, it should be used together with standard HF therapies (ACE inhibitors, b-blockers, and diuretics)
in patients with symptomatic HF to reduce hospitalizations.

• Doses should be adjusted to achieve plasma digoxin concentration of 0.5 to 1 ng/mL. Higher plasma levels
are not associated with additional benefits but may increase the risk of toxicity.

• Most patients with normal renal function can achieve this level with a dose of 0.125 mg/day
• Those receiving interacting drugs e.g amiodarone should receive
0.125mg every other day.
 Intravenous inotropic agents such
as phosphodiesterase (PDE) inhibitors
and beta-adrenergic receptor
agonists are used in selected patients with
HF requiring short-term or longer-term
hemodynamic support.
Milrinone

• Milrinone is a bipyridine derivative that inhibits phosphodiesterase III and produces positive inotropic and
arterial and venous vasodilating effects; hence, milrinone has been referred to as an inodilator.
• It has supplanted the use of amrinone, which has a higher rate of thrombocytopenia.

• During IV administration, milrinone increases stroke volume (and cardiac output) with little change in heart
rate.
• Milrinone should be used cautiously as a single agent in severely hypotensive HF patients because it will not
increase, and may even decrease, arterial blood pressure.

• The usual loading dose of milrinone is 50 mcg/kg over 10 minutes.

• the loading dose should be eliminated because of the risk of hypotension. Most patients are simply started on
the maintenance continuous infusion of 0.25 mcg/kg/min (up to 0.75 mcg/kg/min).

• The most notable adverse events are arrhythmia, hypotension, and, rarely, thrombocytopenia. Patients should
have platelet counts determined before and during therapy.

• Phosphodiesterase inhibitors such as milrinone can relieve symptoms and improve hemodynamics in patients
with advanced congestive heart failure. We retrospectively evaluated the hemodynamic and clinical outcomes
of long-term combination therapy with intravenous milrinone and oral β-blockers in 65 patients with severe
congestive heart failure (New York Heart Association class IV function and ejection fraction <25%)
refractory to oral medical therapy. Fifty-one patients successfully began β-blocker therapy while on
intravenous milrinone. Oral medical therapy was maximized when possible. The mean duration of milrinone
treatment in this combination-treatment group was 269 days (range, 14–1,026 days). Functional class
improved from IV to II–III with milrinone therapy. Twenty-four such patients tolerated β-blocker up-titration
and were successfully weaned from milrinone
Dopamine
• Dopamine should be generally avoided in the decompensated HF, but
its pharmacology actions may be preferable to dobutamine or
milrinone in the patient with marked systemic hypotension or
cardiogenic shock.
• Dopamine produce dose dependent hemodynamic effect because of
its relative affinity for alpha1 beta1 beta2.
• Positive inotropic effects mediated primarily by b1-receptors become more prominent with doses of 2 to 5
mcg/kg/min.
• At doses between 5 to 10 mcg/kg/min, chronotropic and a1-mediated vasoconstricting effects become more
prominent.
Nitroprusside

• Sodium nitroprusside is a mixed arterial-venous vasodilator that acts directly on vascular smooth muscle to
increase cardiac index and decrease venous pressure

• Despite its lack of direct inotropic activity, nitroprusside exerts hemodynamic effects that are qualitatively
similar to those of dobutamine and milrinone.

• However, nitroprusside generally decreases PAOP, SVR, and blood pressure more than those agents do.
• Hypotension is an important dose-limiting adverse effect of nitroprusside and other vasodilators

• Therefore, nitroprusside is primarily used in patients who have a significantly elevated SVR and often
requires invasive hemodynamic monitoring.
• Nitroprusside is effective in the short-term management of severe HF in a variety of settings (e.g., acute MI,
valvular regurgitation, after coronary bypass surgery, decompensated HF).

• Generally, it will not worsen, and may improve, the balance between myocardial oxygen demand and supply.
However, an excessive decrease in systemic arterial pressure can decrease coronary perfusion and worsen
ischemia.

• Nitroprusside has a rapid onset and a duration of action of less than 10 minutes, which necessitates use of
continuous IV infusions.
• It should be initiated at a low dose (0.1 to 0.2 mcg/kg/min) to avoid excessive hypotension, and then
increased by small increments (0.1 to 0.2 mcg/kg/min) every 5 to 10 minutes as needed and tolerated
• Because of a rebound phenomenon after abrupt withdrawal of nitroprusside in patients with HF, doses should
be tapered slowly when stopping therapy.
Nitroglycerin

• The major hemodynamic effects of IV nitroglycerin are decreased preload and PAOP because of functional
vasodilation and mild arterial vasodilation.

• It is used primarily as a preload reducer for patients with pulmonary congestion. In higher doses,
nitroglycerin displays potent coronary vasodilating properties and beneficial effects on myocardial oxygen
demand and supply, making it the vasodilator of choice for patients with severe HF and ischemic heart
disease.

• Nitroglycerin should be initiated at 5 to 10 mcg/min (0.1 mcg/kg/min) and increased every 5 to 10 minutes as
necessary and tolerated. Maintenance doses usually range from 35 to 200 mcg/min (0.5 to 3 mcg/kg/min).
Hypotension and an excessive decrease in PAOP are important dose limiting side effects.
• Some tolerance develops in most patients over 12 to 72 hours of continuous administration.
MECHANICAL CIRCULATORY SUPPORT
(Intra aortic Balloon Pump)

• The intra aortic balloon pump (IABP) is typically employed in patients with advanced HF who do not
respond adequately to drug therapy, such as those with intractable myocardial ischemia or patients in
cardiogenic shock.

• IABP support increases cardiac index, coronary artery perfusion, and myocardial oxygen supply accompanied
by decreased myocardial oxygen demand.

• IV vasodilators and inotropic agents are generally used in conjunction with the IABP to maximize
hemodynamic and clinical benefits.
Ventricular Assist Devices

• Ventricular assist devices are surgically implanted and assist, or in some cases replace, the pumping functions
of the right and/or left ventricles.

• Ventricular assist devices can be used in the short-term (days to several weeks) for temporary stabilization of
patients awaiting an intervention to correct the underlying cardiac dysfunction.

• They can also be used long term (several months to years) as a bridge to heart transplantation. Permanent
device implantation has recently become an option for patients who are not candidates for heart
transplantation.