In low output cardiac failure, the heart is unable to maintain a normal pump function.  This would be the case in myocardial failure due to MI, for example.  In contrast, high output cardiac failure involves a heart that maintains its pump function (ex: still pumps 5L/min etc.) but the needs of the body still aren't met.  This could be due to conditions such as anemia or shunts.

Low= body requires normal function, but heart can't work normally.  High= body requires higher than normal output that heart can't meet.

These are signs of myocardial hypertrophy, which may be caused by increased preload, increased afterload, and myocyte loss.

A problem with hypertrophy is that the capillary network may not increase in proportion to the myocardial mass, increasing the likelihood of ischemia.

Digoxin is a cardiac glycoside.  It specifically inhibits the Na+/K+ ATP pump.  This leads to an increased intracellular concentration of Na+.  A result of this is that the Na+/Ca++ exchanger is inhibited, thereby increasing intracellular Ca++ also.  (Remember: intracellular Ca++ concentrations mirror intracellular Na+)

More Ca++ is taken up into the sarcoplasmic reticulum during diastole, allowing for more intracellular Ca++ release during contraction.  This ultimately increases heart contractility.

This action by digitalis is independent of sympathetic stimulation!

Digitalis causes disturbances in the repolarization phase of the heart that lead to an increased risk of arrhythmias.  These disturbances can be visualized on the ECG as:

Longer PR interval

Shorter QRS duration

Shorter QT interval

ST segment depression

Flattened/inverted T wave

Digitalis can act as a parasympathomimetic, directly stimulating the vagal nucleus to induce bradycardia.  It also has a direct depressive action on the SA and AV nodes.  This second mechanism is the main mechanism by which digitalis would impact a transplanted heart, which is devoid of vagal innervation.

Finally, because digitalis helps restore CO in a failing heart, it relieves the burden placed on the sympathetic system to maintain CO, and the sympathetic induced tachycardia subsides.

This woman has digitalis toxicity.  Adjust her dosage!  She can be given lidocaine for the arrhythmias.

If the toxicity is life threatening, for example it pushes the woman into asystole, the digitalis antibody "Digibind" can be used as an antidote.

Digitalis is contraindicated in any situation where there is diastolic dysfunction.  The increased Ca++ levels caused by digitalis impairs diastolic relaxation, so this would compound the problem.  Additionally, any ventricular arrhythmias or nodal blocks would also make digitalis contraindicated.  Because of its direct inhibitory effect on the AV node, digitalis will only worsen any pre-existing nodal block.  Additonally, limiting the conduction through the AV node, digitalis will allow any ventricular arrhythmia to have free reign over the ventricular contraction (i.e. it will block impulses from atria and AV node from overriding the dangerous ventricular arrhythmia).

Digitalis is used in systolic heart failure and atrial fibrillation

At low doses, dopamine is a pure D1 agonist.  This causes vasodilation in the renal and mesenteric beds.

At intermediate doses, dopamine is a D1, B1, and B2 agonist.

At high levels, Dopamine is a D1, B1, B2, and A1 agonist.  With heart failure, activation of this last receptor is unwanted, as it will raise TPR and increase the work of the heart (increased afterload).

Dopamine should be given at intermediate doses, because it will vasodilate the renal arteries(D1) and stimulate the heart (B1, B2).

Dobutamine is also commonly given.  In fact, these two drugs are often titrated according to the patient's symptoms.  If the heart starts failing, dobutamine is pushed.  If the kidneys start suffering, more dopamine is given...

Milrinone

Inamrinone

Milrinone is a phosphodiesterase inhibitor used in heart failure.  It preferentially inhibits phosphodiesterase isoenzyme 3, found in carciac muscle.  This phosphodiesterase inactivates cAMP.  As we know, cAMP is responsible for increasing the contractility of the heart.  Phosphodiesterases normally take this away, so by inhibiting them, we can increase the Ca++ levels and make the heart beat more forcefully.

In the periphery, cAMP increase means inactivation of MLCK and vasodilation, thereby decreasing peripheral resistance!  (This last effect is why milrinone can cause hypotension and syncope).

Milrinone is reserved for acute cases where other drugs have failed to adequately restore cardiac function.  It cannot be given chronically.

Stage A = subclinical. Often discovered by ECG abnormalities.  No symptoms present. 

Stage B = Asymptomatic under normal situation, but there are structural problems with the heart.  May place limits on excessive physical activity etc.

Stage C = Symptomatic, even with normal activity

Stage D = Patient essentially bedridden.  Requires continuous monitoring

Vasodilators can reduce both preload and afterload.  In fact, ACE inhibitors and the Angiotensin receptor antagonists are the preferred vasodilators because they cause a balanced reduction in both of these areas. 

Other vasodilators include nitrates, nitroprusside, milrinone, and hydralazine.

ACE inhibitors reduce angiotensin II levels.  Angiotensin II is responsible for increased TPR, which increases afterload.  Angiotensin II also promotes aldosterone release and therefore salt and water retention.  This increases preload.  By blocking angiotensin II, ACE inhibitors are able to reduce preload and afterload.

ACE inhibitors are normally combined with a loop diuretic as the treatment for heart failure patients.

Nesiritide is brain natriuretic peptide.  It activates guanylyl cyclase, thereby increasing cGMP synthesis.  cGMP promotes NO-mediated vasodilation.

This causes hypotension and may promote renal failure, so this drug is not used in chronic treatment, only emergencies.

SPironolactone is a potassium sparing diuretic that acts by antagonizing aldosterone receptors.  Aldosterone increase is an effect of angiotensin II.  Remember that we want to reduce the impacts of angiotensin in heart failure, and spironolactone helps to accomplish this more completely.

Aldosterone antagonists help to limit the remodeling that occurs in the heart due to cardiac failure.

Thiazide diuretics cause hypokalemia and hypercalcemia.  Recall, the increased tubular fluid flow maintains the K+ gradient, promoting its excretion.  The inhibition of Na+ reabsorption by the tubular cells lowers intracellular Na+, thereby favoring the Ca++/Na+ exchanger.  Na+ enters from the blood, Ca++ is pumped into the blood resulting in hypercalcemia. 

Hypercalcemia and hypokalemia are two conditions that predispose patients to digoxin toxicity!  The hypercalcemia increases the Ca++ trapping in the cells, augmenting digoxin's effects.  The hypokalemic state is inhibitory toward the Na+/K+ pump, yielding additive inhibition when combined with digoxin!

Digoxin because it will accomplish two things:

1) digoxin will increase contractility, restoring stroke volume and systolic blood pressure.  This will relieve the strain placed on the sympathetic system.

2) digoxin will protect the ventricles from the rapidly fibrillating atria due to its direct depressive effect on the AV node!

Furosemide, a loop diuretic, should be given to heart failure patients.

Mannitol, the osmotic diuretic, is absolutely contraindicated in heart failure patients because it can precipitate pulmonary edema.  It will cause an initial transient increase in ECFV, which the heart cannot compensate for, so the back pressure will promote pulmonary edema.

Instead, furosemide would be a drug of choice