Restrictive Cardiomyopathy: Amyloid, Diastolic Dysfunction, and Kussmaul’s Sign

Restrictive cardiomyopathy is the least common type of cardiomyopathy. The restriction refers primarily to diastolic dysfunction (ie: problems with relaxation of the heart); systolic function is generally well preserved. From a clinical perspective the restrictive cardiomyopathies present similarly to the hypertrophic cardiomyopathies.

There are two main causes of restriction: infiltration of the heart muscle with abnormal substances or scarring of the heart muscle. Each of these causes has many underlying etiologies, a few of which are listed below.

   (1) Infiltration
        (a) Amyloidosis
        (b) Sarcoidosis
        (c) Storage diseases
            (i) Hemochromatosis
            (ii) Glycogen storage diseases
   (2) Fibrosis and scarring
        (a) Post-radiation
        (b) Endomyocardial fibrosis

Regardless of the cause, the heart muscle gets "gunked up" with stuff that shouldn’t be there. The result is decreased contractile ability.

Signs and Symptoms

Patient’s with restrictive cardiomyopathy often present with signs and symptoms of diastolic dysfunction. Pulmonary edema (ie: fluid in the lungs) results in dyspnea (difficulty breathing), paroxysmal nocturnal dyspnea (waking up gasping for air), and orthopnea (inability to lay flat secondary to shortness of breath). Reduced cardiac output results in fatigue, dizziness, and weakness.

On physical exam, Kussmaul’s sign can sometimes be appreciated. Kussmaul’s sign occurs when you can see the jugular vein distend when a patient inspires (breathes in). Normally jugular venous distension decreases with inspiration as venous return to the heart increases due to decreased intrathoracic pressure. However, in restrictive cardiomyopathy the ventricle cannot accommodate the increased blood flow and it backs up into the jugular veins during inspiration, hence the paradoxical worsening.

In addition, signs of systemic volume overload can occur including hepatomegaly (ie: an enlarged liver), ascites (ie: fluid in the abdomen), and bilateral lower extremity edema (ie: leg swelling). Arrhythmias are also common because amyloid deposits can wreak havoc on the conduction system of the heart.

Diagnosis and Work-Up

It is important to distinguish restrictive cardiomypathy from restrictive pericarditis, which is treatable. The gold standard test is a myocardial biopsy, which will reveal infiltrating substances in restrictive cardiomyopathy. MRI and CT can show a thickened pericardium, which is more consistent with restrictive pericarditis.

Treatment and Prognosis

Treatment is aimed at the underlying cause. For example, chemotherapy for multiple myeloma or phlebotomy for hemochromatosis can slow disease progression. Since diastolic function is most affected, treatment is aimed at ensuring adequate filling time for the left ventricle. Diuretics should be used cautiously because patient’s are dependent on higher blood volumes to fill as much of the restricted ventricle as possible. Digoxin and vasodilator therapies are usually not helpful since systolic function is usually well-preserved.

Prognosis is generally poor unless treatment of the underlying condition is curative.


Restrictive cardiomyopathy is caused by infiltrative processes (most commonly amyloidosis). Physical exam reveals signs of diastolic dysfunction resulting in blood backing up in the lungs and body. The gold standard for diagnosis is myocardial biopsy, although this is not routinely performed in clinical practice. Treatment is aimed at the underlying cause, if identifiable. In addition, since diastolic dysfunction is present, treatments should be used that allow the heart adequate time to fill.

Related Articles

References and Resources

Systemic Vascular Resistance: Radius, Length, Viscosity

The systemic vascular resistance is the resistance that blood “sees” as it travels throughout the circulatory system of the body.

It is controlled by three different factors: length of the blood vessel (l), radius of the blood vessel (r), and the viscosity of the blood (η). The equation that relates these three factors to resistance is known as Poiseuilles’ equation:

R ≈ (η x l) / r4

Let’s discuss how each of the factors above influences resistance. The longer the vessel, the more likely blood will sludge and stick up against the walls; this tendency intuitively causes an increase in overall resistance. Blood vessel length does not typically change during adulthood, therefore its contribution to vascular resistance in humans is relatively constant.

When blood is more viscous than usual the resistance also increases. For example, molasses flows very slowly because it is highly viscous; blood is no different. There are a few uncommon instances in human physiology where blood viscosity increases; therefore, like vessel length, its contribution to vascular resistance is also relatively constant.

The most important parameter is the radius of the vessel. When the radius of a vessel shrinks, the resistance increases; when the radius of a vessel dilates, the resistance drops. Imagine trying to pump a set amount of fluid through a small opening versus a larger opening. There is much less resistance encountered through the larger opening. The same is true for large and small blood vessels. Even more importantly, as indicated by Poiseuille’s equation above, when the radius of a vessel is halved, the resistance increases by 16 fold! Therefore, even small changes in blood vessel diameter can have dramatic consequences on the bodies’ vascular resistance.

How the Body Controls Resistance

How do you think the body controls resistance most effectively? You guessed it! By controlling the radius of blood vessels. When there is an abnormal drop in vascular resistance, the body compensates by pumping out hormones (ie: epinephrine and norepinephrine); these hormones cause muscle cells surrounding blood vessels to constrict. Constriction leads to a decreased radius of the vessel, which leads to increased resistance.

Clinical Measurements

How do you measure systemic vascular resistance? Well, first off, systemic vascular resistance is not measured, but is calculated from other cardiovascular vital signs such as the mean arterial pressure (MAP), cardiac output (CO), and central venous pressures (CVP). The equation that relates these three values to resistance is:

SVR = [(MAP – CVP) / CO] x 80

Mean arterial pressure is a sort-of average between the systolic and diastolic blood pressure readings. It can be calculated using blood pressures obtained from an arterial catheter or a blood pressure cuff.

Central venous pressures are normally low, and do not contribute much to vascular resistance, but when very accurate measurements are needed they can be obtained from a central venous and/or a pulmonary artery catheter.

Cardiac output can be obtained from a pulmonary artery catheter if accurate values are needed; it can also be roughly estimated from a cardiac echocardiogram (ie: an ultrasound of the heart).

Role in Disease

So what’s the big deal? Why all this talk about vascular resistance? Vascular resistance is important because it is one determinant of blood pressure, and therefore organ perfusion.

The mean arterial pressure is calculated by multiplying the cardiac output by the systemic vascular resistance, and then adding the result to the central venous pressure (MAP = CO x SVR + CVP, a reorganization of the equation above).

Since the mean arterial pressure is the driving force behind the delivery of blood and oxygen to the organs, it is of vital importance that it stays above a certain threshold. Otherwise organs will not receive enough oxygen and will eventually die. One way of ensuring that the mean arterial pressure stays within a set range is for the body to constrict and/or dilate the vessels as needed.

On the flip side, if systemic vascular resistance is too "clamped" down then hypertension occurs. If severe enough, the heart may not be able to generate enough force to eject an adequate amount of blood into the tightened arterial system, which over time could result in systolic heart failure.


Systemic vascular resistance is the resistance blood sees as it travels throughout the bodies blood vessels. It is influenced by the length and radius of the blood vessel(s), as well as the viscosity of blood. It is calculated from the mean arterial pressure, central venous pressure, and cardiac output. Systemic vascular resistance plays a vital role in maintaining blood pressures within set ranges so that organ perfusion is maximized.

References and Resources

Cardiac Output: Pump, Pump, Squeeze

The cardiac output (CO) measures how much blood the heart pumps per minute. It is directly related to the stroke volume (SV) and heart rate (HR). The stroke volume is the amount of blood in the left ventricle of the heart just before it contracts. The cardiac output is calculated by multiplying the heart rate by the stroke volume (CO = HR x SV).

The cardiac output is related to Ohm’s law, which in electrical terms states that the change in voltage of a circuit is equal to the flow of current, I, multiplied by the resistance, R, of the circuit (ΔV = I x R).

Like electrical current in a circuit, blood flows in a circular pathway from the left ventricle, through the body, where it eventually ends up in the right ventricle. We can change Ohm’s law to govern hemodynamics by stating that the change in voltage is equivalent to the change in pressure between the aorta and right atrium (mean arterial pressure and central venous pressures, respectively), flow of current is equal to the amount of blood pumped per unit time (ie: cardiac output), and resistance is equal to the resistance the blood sees as it travels through the vessels of the body (aka: the systemic vascular resistance).

Therefore, if we re-write Ohm’s law for the hemodynamics of cardiac output we get: central venous pressure (CVP, measured in mmHg) subtracted from the mean arterial pressure (MAP, measured in mmHg) is equal to cardiac output (CO, measured in liters/minute) multiplied by the systemic vascular resistance (SVR, measured in dynes-s / cm5), or:

(MAP – CVP) = (CO x SVR) / 80
(ΔV = I x R)

Doing a simple mathematical rearrangement of the equation above we get:

CO = [(MAP – CVP) / SVR] x 80
*** The 80 in the equation is a conversion factor to convert Wood to metric units ***.

In essence, the cardiac output is directly proportional to the difference in blood pressure between the left (arterial side) and right (venous side) sides of the body, and inversely proportional to the vascular resistance. In other words, if the pressure difference between the arterial and venous side of the body decreases the cardiac output will fall. Along the same lines, if the systemic vascular resistance increases then cardiac output will decrease.

Clinical Measurements

How do you clinically measure the components that constitute the cardiac output?

The most reliable, but invasive way is to use a pulmonary artery catheter, also known as a "Swan Ganz" catheter. The catheter is inserted into the pulmonary artery and advanced until it “wedges” in a small branch of the pulmonary arterial tree. From there a balloon in the tip of the catheter is inflated to keep it in place. At this location the tip of the catheter is effectively measuring the pressure of blood in the left atrium (ie: the "pulmonary artery wedge pressure"). Using the catheter, and various methods such as the thermodilution technique, the cardiac output and/or stroke volume can be measured directly.

Unfortunately, the use of Swan-Ganz catheters are fraught with serious problems such as arrhythmias and infection. Therefore, other less invasive techniques such as echocardiography with doppler (ie: an ultrasound of the heart) can be used to estimate cardiac output and stroke volume.

The other elements of cardiac output can also be measured clinically. The mean arterial pressure is calculated from the systolic and diastolic blood pressures, which are measured from a cuff or arterial catheter. Central venous pressure can be measured with a central venous catheter (ie: a "central line").

Role in Disease

A normal cardiac output is roughly 5.5 L/min for an average sized male and 5.0 L/min for an average sized female. However, in individuals with diseased heart muscle the pumping ability of the heart is reduced. The result is a decrease in cardiac output.

So what’s the big deal? A fall in cardiac output means that the body sees less oxygenated blood per minute. Every organ in the body requires oxygen to function properly. If cardiac output is decreased the organs may not receive enough oxygen to do their job. In super severe cases, when cardiac output approaches zero, cardiogenic shock occurs. If no oxygen reaches the organs multi-organ failure occurs and the patient may die.


Cardiac output is related to the stroke volume, heart rate, systemic vascular resistance, and difference in pressure between the arterial and venous sides of the body. When cardiac output drops the bodies’ organs receive less oxygen per unit time. In severe cases this may lead to organ death.

Related Articles

References and Resources