Management of Congestive Heart Failure, by Christina VanderPluym.

My name is Christina VanderPluym. I'm the Director of the Ventricular Assist Device

Program at Boston Children's Hospital. And today I'm going to speak about heart failure

in children, focusing on management strategies.

In our first section, we discussed the pathophysiology and diagnosis of heart failure. And in the

subsequent session, we're going to discuss management of congestive heart failure. When

thinking about the management of heart failure, we first must consider what are the goals

for therapeutic intervention? And following this, we'll then look into the components

of therapy, be it either surgical or catheter based therapies, pharmacological and non pharmacological

therapies. And then we will focus on preventing morbidity, or complications related to heart

failure. Specifically, intracardiac thrombus, arrhythmias, and nutritional and growth deficiencies.

Let's begin with the goals of therapeutic intervention. The goals of therapy for heart

failure include relieving symptoms of heart failure, such as congestion and low cardiac

output, decreasing morbidity, such as those related to intracardiac thrombi and arrhythmia,

and including the risk of hospitalization itself. To slow, or even potentially reverse

the progression of heart failure, to improve patient survival, and importantly, improve

patients' quality of life.

Next we move on to the components of therapy. Management of heart

failure depends firstly on the etiology and pathophysiology of heart failure. This was

further described in our first section, but broadly consists of pump dysfunction, volume

overload, or pressure overload. Many children presenting in heart failure may have a combination

of these types of dysfunction, be it either pump dysfunction with volume or pressure overload,

or one of these in isolation.

We must also consider the severity of heart failure. We can classify severity using a

multitude of different classification systems including New York Heart Association classification,

which has been most widely described and used in adults, the Ross classification, which

is most commonly used in children, as well as staging of heart failure from stage A to

D, with stage A consisting of those patients with no symptoms and otherwise normal cardiac

function, but who may be at risk of cardiac dysfunction, and stage D, those with end stage

heart failure refractory to maximum medical management.

Another consideration of management therapies in children is how do they present with their

symptoms? For patients who present with symptomatic heart failure, treatment must also be focused

at what type of symptoms they present with, be it either congestion or low profusion,

or a combination of both. The ideal patient is that person who presents well-profused

with no evidence of congestion, and ultimately, no treatment is warranted at that time. This

is in converse to patients who may present with good profusion, however with evidence

of congestion-- be it either pulmonary edema, peripheral edema, or ascites-- and these patients

may benefit from non-pharmacological therapies, such as fluid restriction, or pharmacological

therapy, such as intravenous or oral diuretics.

There are also those patients who present with evidence of low profusion secondary to

poor cardiac output. They may also present with signs or symptoms of congestion or no

congestion. And in the setting of a patient being cold and dry, they may benefit from

fluid resuscitation, plus or minus the addition of inotropic intravenous medications.

And then there are those patients who present with evidence of poor profusion, as well as

evidence of congestion, and these patients may benefit from fluid restriction, diuretic

therapy, as well as inotropic medication. As you can see, the treatment strategies for

heart failure it can be very varied, and one must always consider not only the pathophysiology

or the severity, but the symptoms that we are trying to target.

In addition to heart failure therapy, we must also try to identify and correct all non-cardiac

factors that may be contributing to cardiac dysfunction or poor perfusion. These include

sepsis, or active infection, metabolic derangements, such as acidosis, anemia that may be impairing

oxygen delivery to end organs and renal failure. Renal failure and heart failure are two significant

problems that sometimes require very different treatment strategies. While heart failure

requires low systemic arterial pressures and lower volumes, renal failure, unfortunately,

requires the opposite, with higher systemic arterial pressures and more volume. As such,

this can be a significant challenge to the treating physician.

Also we must consider any surgical or catheter based therapies that may correct either volume

loading or pressure loading anatomical defects. Let's move on to pharmacological heart failure

therapies. These therapies are used in patients with either pump dysfunction, otherwise known

as systolic dysfunction, with a goal to improve function and/or stabilize or relieve symptoms

of poor output. It can also be used for patients with poor ventricular relaxation, otherwise

known as diastolic dysfunction with the goal to improve pump compliance and relieve symptoms

of congestion. And lastly, can be used in patients with normal pump function in the

setting of symptoms of congestion.

Most add-on heart failure medication has come from studies in adult patients, with

only very small trials conducted in children. This is due to the fact that we are unable

to conduct large trials in children because the prevalence of heart failure in children

is relatively low as compared to our adults. Additionally, there are many different causes

of heart failure in children, resulting in significant heterogeneity for large studies.

Let's begin with drugs for mild to moderate heart failure, stages B and C. There's a large

armamentarium of medications that can be used for symptomatic heart failure in the setting

of poor ventricular function or congestion. These include diuretics, with the goal to

reduce filling pressures and reduce symptoms of congestion, to digoxin to increase inotropy,

or contraction of the ventricle. Angiotensin converting enzyme inhibitors to reduce afterload

and decrease the LV workload. Beta blockers to reduce the maladaptive sympathetic activation

of the heart to reduce heart rate and allow for more diastolic filling time. And lastly,

pulmonary vasodilators that decrease pulmonary vascular resistance and decrease the workload

of the right ventricle.

Let's begin with diuretics. Diuretics decrease preload by promoting natriuresis and relieve

symptoms of volume overload, be it other pulmonary or peripheral edema. They are generally used

in children with stage C and D heart failure. This is symptomatic heart failure secondary

to ventricular dysfunction, or end-stage heart failure refractory to other medical managements.

There are multiple different classes of diuretics. And these include loop diuretics that inhibit

sodium and chloride reabsorption in the thick ascending loop of Henle. These include furosemide,

bumetanide, and torsemide.

Next are thiazide diuretics that inhibit reabsorption of sodium and chloride in the convoluted tubules

of the kidney. These include chlorothiazide, hydrochlorothiazide, and metolazone. And lastly,

aldosterone antagonists that decrease sodium reabsorption and potassium excretion in the

collecting ducts of the kidney, including spironolactone and eplerenone. These medications

are used in conjunction with loop and thiazide diuretics, and they have been shown to reduce

mortality and morbidity in patients with heart failure, in addition to standard medications.

Let's move on to digoxin. Digoxin has a positive inotropic effect, mediated by the sodium potassium

ATPase pump and increases intracellular calcium. Intracellular calcium is imperative to increase

the squeeze or the contraction of the ventricle. Additionally, it has a negative chronotropic

effect that slows the atrial conduction and vagotonic properties that counter the sympathetic

upregulation, which is maladaptive for heart failure. This ultimately decreases heart rate,

and allows for more time for the ventricle to fill. It's generally used in infants and

children with stage C heart failure for symptomatic relief. Benefits of digoxin can be actually

seen at much lower doses than traditionally thought, with trough levels of only 0.5 to

1 nanogram per mL, resulting in lower risk of adverse effects, such as arrhythmias.

Next are renin-angiotensin-aldosterone inhibition. The renin-angiotensin-aldosterone system is

a very active system in heart failure. It leads to increased sympathetic tone, which

is a compensatory for low cardiac output in the short term, but becomes maladaptive over

time, resulting in tachycardia, fluid retention, and hypertension. Inhibition of this system

are target medications for heart failure. And these include Angiotensin Converting Enzyme

inhibitors, otherwise known as ACE inhibitors, and Angiotensin Receptor Blockers, or ARBs.

Angiotensin Converting Enzyme inhibitors inhibit formulation of angiotensin II, which is a

potent vasoconstrictor that promotes myocite hypertrophy and fibrosis. ACE inhibitors improve

survival in adults with symptomatic heart failure in clinical trials, and reduce the

rate of progression of heart failure. However, there are a limited small studies in ACE use

in children.

Experts suggest that use of ACE inhibitors in children with pump dysfunction, such as

those with stage B or C heart failure, may be of benefit. However, close monitoring of

blood pressure and renal function is imperative, as ACE inhibitors will decrease patients' blood

pressure. And this may adversely affect already tenuous renal function. Enalopril, which has

twice-daily dosing, is traditionally used for larger children. And captopril, which

is three times daily dosing, is used for smaller infants and children.

The next medication is Angiotensin Receptor Blockers, otherwise known as ARBs. There is

limited data on the effectiveness for use in children. However, there are smaller case

studies demonstrating its use as an alternative to ACE inhibitors when there are significant

side effects or intolerance of ACE inhibition due to ACE-induced cough or angioedema.

Beta blockers. Beta blockers counteract the maladaptive effects of chronic sympathetic

activation. In adults, they improve survival, reverse LV remodeling, and decrease myocardial

fibrosis. It should be noted that they should only be added once stable on other heart failure

medications, including ACE inhibitors and diuretics. Carvedilol is generally the recommended

beta blocker for use in children with LV dysfunction, and dosing of carvedilol can be started very

low, generally at 1/8 of the eventual target dose, at 0.05 milligrams per kilo per dose

twice daily, and increased cautiously every two weeks to minimize side effects. Side effects

of beta blockers include dizziness, fatigue, hypotension, bradycardia, and hypoglycemia.

Pulmonary vasodilators. Pulmonary vasodilators are used in the setting of right-sided heart

failure secondary to elevated pulmonary vascular resistance. Pulmonary vascular resistance

may be increased due to a multitude of different reasons, including abnormalities of the pulmonary

vasculature, such as idiopathic pulmonary hypertension, or secondary to left heart failure

with subsequent elevated left-sided pressures resulting in secondary pulmonary hypertension.

Phosphodiesterase-5 inhibitors, sildenafil, is the most commonly used. And this has been

associated with improved LV function, functional capacity, and quality of life in adults. There

are, to date, limited large studies in children. However, there are a multitude of small studies

demonstrating its usefulness in a multitude of different congenital anatomies, including

Fontan circulation.

Let's move on to drugs for advanced heart failure-- namely, heart failure stage D. These

include inotropes, which are used for acute exacerbations of heart failure with the goal

to increase cardiac output by contraction and heart rate response. Catecholamines are

the most frequently used to improve myocardial contractility. Generally we prefer the use

of dopamine in combination with milrinone for decompensated heart failure due to the

fact that it not only improves myocardial contractility and relaxation, but it also

reduces peripheral vascular resistance, resulting in a decreased workload for the left ventricle.

Milrinone is a phosphodiesterase-3 inhibitor. It increases contractility, reduces afterload,

and has no significant increase in myocardial oxygen consumption. All of these features

make it very attractive for chronic use in children who are awaiting transplantation.

Infusions of milrinone can commence at 0.25 micrograms per kilo per minute, up to 1 microgram

per kilo per minute. Additionally, this medication has been shown to be effective and safe in

an outpatient setting.

Let's move on to non-pharmacological therapies for heart failure, which are as equally important

as pharmacological therapies.

Nutrition. Growth failure, feeding intolerance, and anorexia is a common complication, as

well as presenting symptom of children with heart failure. Increasing caloric intake by

fortification with diet is generally necessary in all children with significant symptomatic

heart failure. Additionally, the use of tube feeds via nasogastric, nasojejunal, or direct

surgical gastric tubes may be necessary.

Another primary therapeutic intervention is focused at fluid restriction. Fluid restriction

should be one of the first steps in non-pharmacological treatment of heart failure with symptoms of

congestion. Heart failure may result in maladaptive excessive thirst and water intake, leading

to electrolyte derangements such as hyponatremia and symptoms of congestion and edema. Simply

by limiting fluid intake to high-caloric fluids only and limiting total fluid intake may ameliorate

symptoms of congestion dramatically. They may also limit the use of diuretics that may

have long-term negative effects on renal function.

While there is currently no recommended total fluid intakes for children, general guidelines

suggest infants having around 100 cc's per kilo per day, children weights 10 to 30 kilos

between 600 to 1 liter per day, and older children and adolescents, between 1 to 2 liters

per day.

For more advanced forms of heart failure, positive pressure ventilation may be necessary.

This may be delivered by invasive methods, such as intubation, or noninvasive, such as

continuous positive pressure. Positive pressure ventilation alleviates respiratory distress

from cardiogenic pulmonary edema. It has also been shown to improve alveolar recruitment,

lung compliance, and decrease LV preload, as well as afterload.

And lastly, for patients with end-stage heart failure, refractory to maximal medical management,

mechanical circulatory support is an option. There currently are many different forms of

mechanical circulatory support that can provide both short and long-term cardio and cardiopulmonary

support. For short-term support, these include Extracorporeal Membrane Oxygenation, otherwise

known as ECMO. And for long-term support, it includes ventricular assist devices. These

can be used as a bridge to transplantation or to stabilize patients with subsequent removal

of the mechanical circulatory support with ventricular myocardial recovery.

Let's move on to preventing morbidity or complications

related to heart failure. There are a multitude of complications that can be related to heart

failure. These include thrombi formation. Intra-cardiac clots can form in the setting

of severe RV or LV dysfunction, leading to either pulmonary embolus, cerebral embolic

strokes, or any other arterial embolic events.

We suggest the use of anti-coagulation, be it unfractionated or low-molecular heparin,

or an oral vitamin K antagonist for severe RV or LV dysfunction. And we suggest the use

of an anti-platelet agent, such as aspirin, in the setting of mild to moderate RV or LV

dysfunction. There are currently no clear guidelines on what ejection fraction should

be used as the cutoff between the use of anti-coagulation or anti-platelet therapy, however many adult

studies demonstrate that an LV ejection fraction less than 30% should be treated with anti-coagulation

to prevent intra-cardiac thrombi formation.

Next is arrhythmias. Decreased ventricular function can lead to ventricular and atrial

enlargement that predispose to sustain atrial and ventricular arrhythmias. As can be expected,

atrial and ventricular arrhythmias can result in significant hemodynamic compromise and

destabilize already marginal patients. As such, medication, ablation, or even implantable

cardioverter-defibrillators are all recommended depending on the severity of the heart failure

and the frequency of arrhythmias.

In summary, there are a multitude of approaches to heart failure, and ultimately they all

depend on the pathophysiology of the underlying cause of the heart failure as well as the

severity of the presentation. In considering patients with heart failure, we must first

consider any surgical or based cath correction of structural heart disease that may be resulting

or contributing to heart failure. Next, we must focus on therapies that are tailored

to the severity of the heart failure.

For stage A patients-- those are those that are at risk of heart failure but who currently

have normal function-- no therapy is recommended. For stage B-- these are patients who are asymptomatic

with abnormal function-- simply an ACE inhibitor may cause regression or remodeling of the

ventricle and normalization of function. For stage C-- patients with symptomatic heart

failure in the setting of abnormal function-- there's a large armamentarium of medications

recommended, such as ACE inhibitors, aldosterone antagonists, beta blockers, digoxin, and diuretics.

Utilization of these therapies must be tailored at what symptoms the patient presents with,

be it congestion or low perfusion. And lastly, for stage D-- patients presenting with end

stage heart failure refractory to oral medications-- the use of intravenous inotropes, diuretics,

ventilation, mechanical circulatory support, and lastly heart transplant are all warranted.

Non-pharmacological therapy is also equally important to pharmacological therapy, including

nutritional support and exercise programs.

And lastly, we must focus on prevention and treating of complications related to heart

failure, both thrombotic events and arrhythmias. Thank you for watching this video on heart

failure management in children.

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