What is CD4 count

CD4 count is a laboratory test that measures CD-4 T lymphocytes (T cells) via flow cytometry. CD4 T cells help to fight infection and play an important role in your immune system function. CD4 count test is an important parameter in human immunodeficiency virus (HIV) management and is used to guide clinical treatment. The CD4 count is a reliable indicator of a patient’s immunologic status and is used to determine the necessity for initiation of prophylactic treatment against opportunistic infections ¹. The CD4 molecule is a member of the immunoglobulin family and primarily mediates adhesion to major histocompatibility complex molecules. CD4 T cells are selectively targeted and infected by HIV. HIV proliferates rapidly during acute infection leading to high levels of viremia and rapid impairment and death of CD4 T cells.

CD4 T cells are white blood cells called helper T lymphocytes or helper T cells that express cluster determinant 4 (CD4) molecules or markers on their surfaces. The CD number identifies the specific type of cell. CD4 cells are sometimes called T-helper cells. CD4 T cells help to identify, attack, and destroy specific bacteria, fungi, and viruses that cause infections. CD4 cells are a major target for HIV, which binds to the surface of CD4 cells, enters them, and either replicates immediately, killing the cells in the process, or remains in a resting state, replicating later.

If HIV goes untreated, the virus gets into the cells and replicates, the viral load increases, and the number of CD4 cells in the blood gradually declines. The CD4 count decreases as the disease progresses. If still untreated, this process may continue for several years until the number of CD4 cells drops to a low enough level that symptoms associated with AIDS begin to appear.

Treatment for HIV infection, called antiretroviral treatment (ART or ARV) or sometimes highly active antiretroviral therapy (HAART), typically involves taking a combination of drugs. This treatment reduces the amount of HIV (viral load) present in your body and reduces the risk of disease progression. When this occurs, the CD4 count will increase and/or stabilize.

CD8 cells are another type of lymphocyte. They are sometimes called T-suppressor cells or cytotoxic T cells. CD8 cells (cytotoxic T cells) identify and kill cells that have been infected with viruses or that have been affected by cancer. CD8 cells (cytotoxic T cells) play an important role in the immune response to HIV infection by killing cells infected with the virus and by producing substances that block HIV replication.

As HIV disease progresses, the number of CD4 cells will decrease in relation to the number of total lymphocytes and CD8 cells. To provide a clearer picture of the condition of your immune system, test results may be reported as a ratio of CD4 to total lymphocytes (percentage).

CD4 and CD8 tests may be used occasionally in other conditions, such as lymphomas and organ transplantation.

CD4 T cells are made in the thymus gland and they circulate throughout your body in the blood and lymphatic system. CD4 count tests measure the number of these cells in your blood and, in conjunction with an HIV viral load test, help assess the status of the immune system in a person who has been diagnosed with HIV infection.

Viral load (HIV RNA). This test measures the amount of virus in your blood. A higher viral load has been linked to a worse outcome.

How is the sample collected for testing?

A health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

How is HIV infection diagnosed?

HIV infection is usually screened for with an HIV antibody test or a combination test for HIV antibody and antigen (p24). If the screening test is positive, it must be followed with another test, such as a second antibody test that can differentiate HIV-1 and HIV-2. If results of the first and second test do not agree, then the next test to perform is an HIV-1 RNA test (nucleic acid amplification test, NAAT). If either the second antibody test or the HIV-1 RNA is positive, then the person tested is diagnosed with HIV infection.

Why do I need a CD4 count?

Your health care provider may order a CD4 count when you are first diagnosed with HIV. You will probably be tested again every few months to see if your counts have changed since your first test. If you are being treated for HIV, your health care provider may order regular CD4 counts to see how well your medicines are working.

CD4 count monitoring is primarily used to assess when to initiate prophylaxis against several opportunistic infections. Although it is also obtained in monitoring response to ART (antiretroviral therapy), CD4 count is, by itself, insufficient in evaluating response to therapy. Viral load monitoring remains the most reliable indicator of treatment response. The CD4 count must be obtained at baseline 3 months after initiation of ART (antiretroviral therapy). It is subsequently monitored every 3 to 6 months during therapy. According to treatment guidelines, less frequent monitoring (every 12 months) may be done after 2 years of ART in patients who have a stable CD4 count of greater than 300 cells/mm³ and consistently undetectable viral load.

Your doctor may include other tests with your CD4 count, including:

• A CD4-CD8 ratio. CD8 cells are another type of white blood cell in the immune system. CD8 cells kill cancer cells and other invaders. This test compares the numbers of the two cells to get a better idea of immune system function.
• HIV viral load, a test that measures the amount of HIV in your blood.

What is CD4 count used for?

A CD4 count is usually ordered along with an HIV viral load when a person is first diagnosed with HIV infection as part of a baseline measurement. After the baseline, a CD4 count will usually be ordered at intervals over time, depending on a few different factors.

A CD4 count may be used to:

• See how HIV is affecting your immune system. This can help your health care provider find out if you are at higher risk for complications from the disease.
• Decide whether to start or change your HIV medicine
• Diagnose AIDS (acquired immunodeficiency syndrome)
  • The names HIV and AIDS are both used to describe the same disease. But most people with HIV don’t have AIDS. AIDS is diagnosed when your CD4 count is extremely low.
  • AIDS is the most severe form of HIV infection. It badly damages the immune system and can lead to opportunistic infections. These are serious, often life-threatening, conditions that take advantage of very weak immune systems.

You may also need a CD4 count if you’ve had an organ transplant. Organ transplant patients take special medicines to make sure the immune system won’t attack the new organ. For these patients, a low CD4 count is good, and means the medicine is working.

Table 1. Recommendations for the timing of CD4 counts and viral load testing

How is CD4 count used?

CD4 counts are most often used, along with an HIV viral load, to evaluate the immune system of a person diagnosed with human immunodeficiency virus (HIV) infection and to monitor effectiveness of antiretroviral treatment (ART or ARV), also called highly active antiretroviral therapy (HAART).

CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection and play an important role in immune system function. They are made in the thymus gland and they circulate throughout the body in the blood. (See the “What is being tested?” section for more details.)

CD4 cells are the main target of HIV. The virus enters the cells and uses them to make copies of itself (replicate) and spread throughout the body. HIV kills CD4 cells, so if an HIV infection is not treated, the number of CD4 cells will decrease as HIV infection progresses.

It is recommended that all individuals diagnosed with HIV infection receive antiretroviral treatment as soon as possible, including pregnant women, to reduce the risk of disease progression. People typically take at least three drugs from two different classes in order to prevent or minimize virus replication and the emergence of drug-resistant strains. Combinations of three or more antiretroviral drugs are referred to as highly active antiretroviral therapy or HAART.

Since CD4 cells are usually destroyed more rapidly than other types of lymphocytes and because absolute counts can vary from day to day, it is sometimes useful to look at the number of CD4 cells compared to the total lymphocyte count. The result is expressed as a percentage, i.e., CD4 percent.

The results can tell a health practitioner how strong a person’s immune system is and can help predict the risk of complications and debilitating opportunistic infections. CD4 counts are most useful when they are compared with results obtained from earlier tests. They are used in combination with the HIV viral load test, which measures the amount of HIV in the blood, to monitor how effective ART is in suppressing the virus and determine the risk of progression of HIV disease.

Sometimes, CD4 tests may be used along with a test for CD8 cells to help diagnose or monitor other conditions such as lymphoma, organ transplantation, and DiGeorge syndrome. CD8 cells are another type of lymphocyte that identify and kill cells that have been infected with viruses or that have been affected by cancer.

CD4 count clinical significance

CD4 count depletion is a consequence of HIV infection and leads to devastating opportunistic infections when left untreated. It affects both CD4 helper T cells in the lymphoid tissue as well as T cells circulating in the peripheral blood. In the natural history of HIV infection, there is an abrupt decline in the CD4 count during acute HIV infection that is usually followed by a rebound as a result of CD8 lymphocyte response to viral replication. Without antiretroviral treatment, the CD4 count will then decline over the next several years.

CD4 cell counts are used to monitor immunologic response to ART. With effective viral suppression, CD4 count is expected to increase by at least 50 cells/microliter after 4 to 8 weeks of treatment and by approximately 100 to 150 cells/microliters increase from baseline at one year. This is then followed by an expected increase of 50 to 100 cells/microliter per year. Several factors such as older age, lower CD4 baseline, and severe immunocompromised status have been associated with a less than expected improvement in the CD4 count while on treatment.

CD4 count is not a reliable indicator of virologic suppression and medication adherence. In patients who develop virologic resistance while on ART, it may take months for the CD4 count to decline and it may even initially increase. Several factors may falsely increase or decrease CD4 cell counts that may not necessarily reflect a patient’s true immunologic status. Inter-laboratory variability must also be taken into consideration. Thus, any significant but unexpected difference between two CD4 count measurements, which is defined as a 30% change in absolute CD4 count or 3% change in CD4 percentage, must be confirmed with a repeat testing.

What is a normal CD4 count

• CD4 count normal range: 500–1,400 cells per cubic millimeter (500–1,400 cells/mm³) ¹

The CD4 count tends to be lower in the morning and higher in the evening. Acute illnesses, such as pneumonia, influenza, or herpes simplex virus infection, can cause the CD4 count to decline temporarily. Cancer chemotherapy can dramatically lower the CD4 count.

Low CD4 count

CD4 results are given as a number of cells per cubic millimeter of blood. Below is a list of typical results. Your results may vary depending on your health and even the lab used for testing. If you have questions about your results, talk to your health care provider.

• HIV CD4 count range: 250–500 cells per cubic millimeter (250–500 cells/mm³). It means you have a weakened immune system and may be infected with HIV.

• AIDS CD4 count range: 200 or fewer cells per cubic millimeter (<200 cells/mm³). It indicates AIDS and a high risk of life-threatening opportunistic infections. The Centers for Disease Control and Prevention (CDC) considers people who have an HIV infection and CD4 counts below 200 cells/mm³ to have AIDS (stage III HIV infection), regardless of whether they have any signs or symptoms.

The CD4 count does not always reflect how someone with HIV disease feels and functions. For example, some people with higher CD4 counts are ill and have frequent complications, and some people with lower CD4 counts have few medical complications and function well.

While there is no cure for HIV, there are different medicines you can take to protect your immune system and can prevent you from getting AIDS. Today, people with HIV are living longer, with a better quality of life than ever before. If you are living with HIV, it’s important to see your health care provider regularly.

What are some common opportunistic infections I might get if I have an HIV infection?

Examples include fungal infections such as candidiasis and other infections such as tuberculosis or those caused by nontuberculosis mycobacteria. The Centers for Disease Control and Prevention (CDC) provides a table with examples of common opportunistic infections.

Table 2. Most common opportunistic infections for people living in the United States

What does the CD4 count test result mean?

A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 500–1,200 cells/mm³ in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).

In general, a normal CD4 count means that the person’s immune system is not yet affected by HIV infection. A low CD4 count indicates that the person’s immune system has been affected by HIV and/or the disease is progressing. However, any single CD4 test result may differ from the last one even though the person’s health status has not changed. Usually, a health practitioner will take several CD4 test results into account rather than a single value and will evaluate the pattern of CD4 counts over time.

CD4 counts that rise and/or stabilize over time may indicate that the person is responding to treatment. If someone’s CD4 count declines over several months, a health practitioner may recommend starting prophylactic treatment for opportunistic infections such as Pneumocystis carinii (jiroveci) pneumonia (PCP) or candidiasis (thrush).

How to increase CD4 count

There’s no cure for HIV/AIDS, but many different drugs are available to control the virus. Such treatment is called antiretroviral therapy, or ART. Each class of drug blocks the virus in different ways. ART is now recommended for everyone, regardless of CD4 T cell counts. It’s recommended to combine three drugs from two classes to avoid creating drug-resistant strains of HIV.

The classes of anti-HIV drugs include:

• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) turn off a protein needed by HIV to make copies of itself. Examples include efavirenz (Sustiva), etravirine (Intelence) and nevirapine (Viramune).
• Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are faulty versions of the building blocks that HIV needs to make copies of itself. Examples include Abacavir (Ziagen), and the combination drugs emtricitabine/tenofovir (Truvada), Descovy (tenofovir alafenamide/emtricitabine), and lamivudine-zidovudine (Combivir).
• Protease inhibitors (PIs) inactivate HIV protease, another protein that HIV needs to make copies of itself. Examples include atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva) and indinavir (Crixivan).
• Entry or fusion inhibitors block HIV’s entry into CD4 T cells. Examples include enfuvirtide (Fuzeon) and maraviroc (Selzentry).
• Integrase inhibitors work by disabling a protein called integrase, which HIV uses to insert its genetic material into CD4 T cells. Examples include raltegravir (Isentress) and dolutegravir (Tivicay).

When to start treatment

Everyone with HIV infection, regardless of CD4 T cell count, should be offered antiviral medication.

Treatment with HIV medicines (ART) is recommended for everyone with HIV. ART helps people with HIV live longer, healthier lives and reduces the risk of HIV transmission.

The Department of Health and Human Services guidelines ⁴ on the use of HIV medicines in adults and adolescents recommend that people with HIV start ART as soon as possible. In people with HIV who have certain conditions, it’s especially important to start ART right away.

HIV therapy is particularly important for the following situations:

• You have severe symptoms.
• You have an opportunistic infection.
• Your CD4 T cell count is under 350.
• You’re pregnant.
• You have HIV-related kidney disease.
• You’re being treated for hepatitis B or C.
• Early HIV infection
• AIDS

Pregnancy

All pregnant women with HIV should take HIV medicines to prevent mother-to-child transmission of HIV. The HIV medicines will also protect the health of the pregnant woman.

All pregnant women with HIV should start taking HIV medicines as soon as possible during pregnancy. In general, women who are already taking HIV medicines when they become pregnant should continue taking HIV medicines throughout their pregnancies. When HIV infection is diagnosed during pregnancy, ART should be started right away.

AIDS

Acquired immunodeficiency syndrome (AIDS) is the most advanced stage of HIV infection. People with AIDS should start ART immediately.

A diagnosis of AIDS is based on the following criteria:

• A CD4 count less than 200 cells/mm³. A low CD4 count is a sign that HIV has severely damaged the immune system.
  OR
• Illness with an AIDS-defining condition. AIDS-defining conditions are infections and cancers that are life-threatening in people with HIV. Certain forms of lymphoma and tuberculosis are examples of AIDS-defining conditions.

HIV-related illnesses and coinfections

Some illnesses that develop in people with HIV increase the urgency to start ART. These illnesses include HIV-related kidney disease and certain opportunistic infections. Opportunistic infections are infections that develop more often or are more severe in people with weakened immune systems, such as people with HIV.

Coinfection is when a person has two or more infections at the same time. Coinfection with HIV and certain other infections, such as hepatitis B or hepatitis C virus infection, increases the urgency to start ART.

Early HIV infection

Early HIV infection is the period up to 6 months after infection with HIV. During early HIV infection, the level of HIV in the body (called the viral load) is often very high. A high viral load damages the immune system and increases the risk of HIV transmission.

ART is an important part of staying healthy with HIV. Studies suggest that these benefits begin even when ART is started during early HIV infection. In addition, starting ART during early HIV infection reduces the risk of HIV transmission.

Treatment can be difficult

HIV treatment plans may involve taking several pills at specific times every day for the rest of your life. Each medication comes with its own unique set of side effects. It’s critical to have regular follow-up appointments with your doctor to monitor your health and treatment.

Some of the treatment side effects are:

• Nausea, vomiting or diarrhea
• Heart disease
• Weakened bones or bone loss
• Breakdown of muscle tissue (rhabdomyolysis)
• Abnormal cholesterol levels
• Higher blood sugar

Treatment for age-related diseases

Some health issues that are a natural part of aging may be more difficult to manage if you have HIV. Some medications that are common for age-related heart, bone or metabolic conditions, for example, may not interact well with anti-HIV medications. It’s important to talk to your doctor about your other health conditions and the medications you are taking.

Treatment response

Your doctor will monitor your viral load and CD4 T cell counts to determine your response to HIV treatment. CD4 T cell counts should be checked every three to six months.

Viral load should be tested at the start of treatment and then every three to four months during therapy. Treatment should lower your viral load so that it’s undetectable. That doesn’t mean your HIV is gone. It just means that the test isn’t sensitive enough to detect it.

1. Li R, Gossman WG. CD4 Count. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470231[↩][↩]
2. Guidelines for the Use of Antiretroviral Agents in HIV-1–Infected Adults and Adolescents, Table 4. Recommendations on the Indications and Frequency of Viral Load and CD4 Count Monitoring[↩]
3. AIDS and Opportunistic Infections. https://www.cdc.gov/hiv/basics/livingwithhiv/opportunisticinfections.html[↩]
4. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/37/whats-new-in-the-guidelines-[↩]

What is PFO

PFO is short for patent foramen ovale, which is a hole in the heart that didn’t close the way it should after birth. During fetal development, a small flap-like opening — the foramen ovale is normally present in the wall between the right and left upper chambers (atria) of the heart. Foramen ovale normally closes during infancy. When the foramen ovale doesn’t close, it’s called a patent foramen ovale or PFO.

PFO occurs in about 25 percent of the normal population, but most people with the PFO never know they have it. A patent foramen ovale is often discovered during tests for other problems. Learning that you have a PFO is understandably concerning, but most people never need treatment for this disorder.

PFO (patent foramen ovale) that abnormally persists into adulthood can contribute to inter-atrial, right-to-left shunting of deoxygenated blood and potential for shunting venous thromboembolism to arterial circulation ¹. This implicates PFO as the underlying pathophysiologic determinant of several conditions including cryptogenic (having no other identifiable cause) stroke, decompression sickness, migraine, platypnea-orthodeoxia syndrome, and acute limb ischemia secondary to emboli ².

Data in 1988 revealed that 30% to 40% of young patients who had a cryptogenic stoke had a PFO ¹. This percentage compared to 25% in the general population. Since that time, the largest target population studied has been patients of all ages with cryptogenic stroke, in whom the frequency of finding a PFO is often double that of the general population ¹. In this population, an optimal secondary prevention strategy is not well defined. Patients with PFO and atrial septal aneurysm who have experienced strokes seem to be at higher risk for recurrent stroke (as high as 15% per year), and secondary preventive strategies are necessary. In another study, 50% of patients with cryptogenic stroke were found to have right-to-left shunting compared to 15% of the controls. Approximately 2/3rds of divers with undeserved (following safe dive profiles) decompression illness, are found to have a PFO. PFOs are especially common in divers with cerebral, inner ear, and cutaneous decompression sickness ³.

PFO primarily increases the risk for stroke from a paradoxical embolism ¹. The risk for a cryptogenic stroke is proportional to the size of the PFO. The presence of an interatrial septal aneurysm in combination with a PFO also increases the risk for an adverse event, perhaps because of increased in situ thrombus formation in the aneurysmal tissue or because PFOs associated with an interatrial septal aneurysm tend to be larger. Despite prior reports concerning paradoxical embolism through a PFO, the magnitude of this phenomenon as a risk factor for stroke remains undefined, because deep venous thrombosis (DVT) is infrequently detected in such patients. In one study, pelvic vein thrombi were found more frequently in young patients with cryptogenic stroke than in those with a known cause of stroke. This may provide the source of venous thrombi, particularly when a source of venous thromboembolism (VTE) is not initially identified ⁴.

By far the most common circumstance prompting the search for PFO is a cryptogenic stroke ¹. Although the prevalence of PFO is about 25 percent in the general population, this increases to about 40 to 50 percent in patients who have stroke of unknown cause, referred to as cryptogenic stroke. This is especially true in patients who have had a stroke before age 40.

Finding out whether you have a PFO is not easy, and it’s something that isn’t usually investigated unless a patient is having symptoms like severe migraines, TIA or stroke. In some cases, the PFO combines with another condition, such as atrial fibrillation (AF), to increase the risk of stroke. There are many causes of stroke and having a PFO accounts for only a very small number. PFO is diagnosed with an echocardiogram. An echocardiogram, also called a cardiac echo, creates an image of the heart using ultrasound. A PFO is usually detected by transthoracic echocardiography, transesophageal echocardiogram (TEE), or transcranial Doppler. Transesophageal echocardiogram is the most sensitive test, especially when performed with contrast media injected during a cough or Valsalva maneuver. Patients with cryptogenic strokes should also be evaluated for the presence of venous thromboembolism (VTE).

Divers with more than one episode of undeserved decompression illness should undergo evaluation for a right to left shunt. A 2015 diving medicine consensus panel recommended contrasted provocative transthoracic echocardiography for this evaluation, because it has a lower complication rate than transesophageal echocardiogram (TEE) and is unlikely to miss a clinically significant PFO ⁵.

If you know you have a PFO (patent foramen ovale), but don’t have symptoms, you probably won’t have any restrictions on your activities.

If someone has a PFO (patent foramen ovale) that is related to symptoms, they can be treated with aspirin, warfarin or catheter closure, depending on the circumstances. The aim of drug treatment is to prevent a clot from forming in the first place. Nothing will close a PFO (patent foramen ovale) except open-heart surgery or a closure device placed by a catheter threaded from the groin through the veins to the heart. Until recently, there were no approved catheter-closure devices designed for PFOs. The FDA has approved a device for patients who’ve had a stroke believed to be caused by a PFO, which reduces the risk of another stroke.

Studies currently demonstrate low recurrent ischemic stroke rates with medical therapy alone ¹. There is some disparity in trials evaluating the superiority of medical and surgical interventions in the prevention of recurrent stroke albeit that risk is apparently low in both approaches. Three randomized clinical trials that totaled more than 2000 patients compared closure of the patent foramen ovale with alternative medical treatment. Data from these trials indicated that PFO offered no benefit compared with medical therapy.

Other studies have shown that patients with cryptogenic stroke and PFO have relatively low outcome rates with medical therapy with or without device closure and that recurrent stroke rates are lower with percutaneously implanted device closure than with medical therapy alone. One study demonstrated that transcatheter closure was found to be superior to medical therapy in the prevention of recurrent neurological events after cryptogenic stroke, and patients taking coumadin had a lower recurrence rate than did those receiving antiplatelet therapy.

Many single-center studies have been published, most have been retrospective, but all have been observational, often with historical controls. The results of these reports have been summarized in meta-analyses supporting the superiority of device closure, frequently with concomitant antiplatelet therapy, versus medical therapy alone. However, prospective studies are lacking.

Figure 1. PFO (Patent Foramen Ovale)

Figure 2. Normal heart blood flow

PFO vs ASD

There are two kinds of holes between the atria (upper chambers of the heart ) of the heart. One is called an atrial septal defect (ASD), and the other is a patent foramen ovale (PFO). Although both are holes in the wall of tissue (septum) between the left and right atrium, their causes are quite different. An ASD is a failure of the septal tissue to form between the atria, and as such it is considered a congenital heart defect, something that you are born with. Generally an ASD hole is larger than that of a PFO. The larger the hole, the more likely there are to be symptoms.

PFOs, on the other hand, can only occur after birth when the foramen ovale fails to close. The foramen ovale is a hole in the wall between the left and right atria of every human fetus. This hole allows blood to bypass the fetal lungs, which cannot work until they are exposed to air. When a newborn enters the world and takes its first breath, the foramen ovale closes, and within a few months it has sealed completely in about 75 percent of us. When it remains open, it is called a patent foramen ovale (PFO), patent meaning open. For the vast majority of the millions of people with a PFO, it is not a problem, even though blood is leaking from the right atrium to the left. Problems can arise when that blood contains a blood clot.

PFO causes

The foramen ovale is a tunnel-like space between the overlying septum secundum and septum primum. The foramen ovale closes in 75% of people at birth when the septum primum and secundum fuse ¹. In utero, the foramen ovale is necessary for the flow of blood across the fetal atrial septum. Oxygenated blood from the placenta returns to the inferior vena cava, crosses the foramen ovale, and enters the systemic circulation. In approximately 25% of people, a PFO persists into adulthood. It’s unclear what causes the foramen ovale to stay open in some people, though genetics may play a role.

An overview of normal heart function in a child or adult is helpful in understanding the role of the foramen ovale before birth.

Normal heart function after birth

Your heart has four pumping chambers that circulate your blood:

• The right atrium. The upper right chamber (right atrium) receives oxygen-poor blood from your body and pumps it into the right ventricle through the tricuspid valve.
• The right ventricle. The lower right chamber (right ventricle) pumps the blood through a large vessel called the pulmonary artery and into the lungs, where the blood is resupplied with oxygen and carbon dioxide is removed from the blood. The blood is pumped through the pulmonary valve, which closes when the right ventricle relaxes between beats.
• The left atrium. The upper left chamber (left atrium) receives the oxygen-rich blood from the lungs through the pulmonary veins and pumps it into the left ventricle through the mitral valve.
• The left ventricle. The lower left chamber (left ventricle) pumps the oxygen-rich blood through a large vessel called the aorta and on to the rest of the body. The blood passes through the aortic valve, which also closes when the left ventricle relaxes.

Baby’s heart in the womb

Because a baby in the womb isn’t breathing, the lungs aren’t functioning yet. That means there’s no need to pump blood to the lungs. At this stage, it’s more efficient for blood to bypass the lungs and use a different route to circulate oxygen-rich blood from the mother to the baby’s body.

The umbilical cord delivers oxygen-rich blood to the baby’s right atrium. Most of this blood travels through the foramen ovale and into the left atrium. From there the blood goes to the left ventricle, which pumps it throughout the body. Blood also travels from the right atrium to the right ventricle, which also pumps blood to the body via another bypass system.

Newborn baby’s heart

When a baby’s lungs begin functioning, the circulation of blood through the heart changes. Now the oxygen-rich blood comes from the lungs and enters the left atrium. At this point, blood circulation follows the normal circulatory route.

The pressure of the blood pumping through the heart usually forces the flap opening of the foramen ovale closed. In most people, the opening fuses shut, usually sometime during infancy.

PFO symptoms

Most people with a PFO (patent foramen ovale) don’t know they have it, because it’s usually a hidden condition that doesn’t create signs or symptoms.

PFO complications

PFOs may be associated with atrial septal aneurysms (a redundancy of the interatrial septum), Eustachian valves (a remnant of the sinus venosus valve), and Chiari networks (filamentous strands in the right atrium) ¹. PFOs may serve as either a conduit for paradoxical embolization from the venous side to the systemic circulation or, because of their tunnel-like structure and propensity for stagnant flow, may serve as a nidus for in situ thrombus formation ⁵.

Generally, a PFO (patent foramen ovale) doesn’t cause complications. But some studies have found the disorder is more common in people with certain conditions, such as unexplained strokes and migraines with aura. PFOs don’t actually cause strokes, but they provide a portal through which a thrombus might pass from the right to the left side of the circulation.

In most cases, there are other reasons for these neurologic conditions, and it’s just a coincidence the person also has a PFO (patent foramen ovale). However, in some cases, small blood clots in the heart may move through a PFO (patent foramen ovale), travel to the brain and cause a stroke.

The possible link between a PFO (patent foramen ovale) and a stroke or migraine is controversial, and research studies are ongoing.

In rare cases a PFO (patent foramen ovale) can cause a significant amount of blood to bypass the lungs, resulting in low blood oxygen levels (hypoxemia).

In decompression illness, which can occur in scuba diving, an air blood clot can travel through a PFO (patent foramen ovale).

In some cases, other heart defects may be present in addition to a PFO (patent foramen ovale).

PFO diagnosis

A doctor trained in heart conditions (cardiologist) may order one or more of the following tests to diagnose a patent foramen ovale:

Echocardiogram

An echocardiogram shows the anatomy, structure and function of your heart.

A common type of echocardiogram is called a transthoracic echocardiogram. In this test, sound waves directed at your heart from a wandlike device (transducer) held on your chest produce video images of your heart in motion. Doctors may use this test to diagnose a patent foramen ovale and detect other heart problems.

Variations of this procedure may be used to identify patent foramen ovale, including:

• Color flow Doppler. When sound waves bounce off blood cells moving through your heart, they change pitch. These characteristic changes (Doppler signals) and computerized colorization of these signals can help your doctor examine the speed and direction of blood flow in your heart. If you have a patent foramen ovale, a color flow Doppler echocardiogram could detect the flow of blood between the right atrium and left atrium.
• Saline contrast study (bubble study). With this approach, a sterile salt solution is shaken until tiny bubbles form and then is injected into a vein. The bubbles travel to the right side of your heart and appear on the echocardiogram. If there’s no hole between the left atrium and right atrium, the bubbles will simply be filtered out in the lungs. If you have a PFO (patent foramen ovale), some bubbles will appear on the left side of the heart. The presence of a PFO may be difficult to confirm by a transthoracic echocardiogram.

Transesophageal echocardiogram

Doctors may conduct another type of echocardiogram called a transesophageal echocardiogram to get a closer look at the heart and blood flow through the heart. In this test, a small transducer attached to the end of a tube is inserted down the tube leading from your mouth to your stomach (esophagus).

This is generally the most accurate available test for doctors to see a PFO (patent foramen ovale) by using the ultrasound in combination with color flow Doppler or a saline contrast study.

Other tests

Your doctor may recommend additional tests if you’re diagnosed with a PFO (patent foramen ovale) and you have had a stroke. Your doctor may also refer you to a doctor trained in brain and nervous system conditions (neurologist).

PFO treatment

Most people with a PFO don’t need treatment. In certain circumstances, however, your doctor may recommend that you or your child have a procedure to close the PFO.

Treatment is aimed at prevention of a secondary event primarily with antiplatelet or anticoagulation therapy or atrial septal device closure. The risk associated with either treatment is low overall, and superiority of one therapy over the other is still contested. Accepted device closure treatment is for large PFOs (greater than 25 mm), and in patients with PFOs who have already had a recurrent neurological event. Any identified venous thromboembolic event involving PFO should be treated with anticoagulation, just as pulmonary embolism would be treated ³.

Reasons for closure

If a PFO is found when an echocardiogram is done for other reasons, a procedure to close the opening usually isn’t performed. Procedures to close the patent foramen ovale may be done in certain circumstances, such as to treat low blood oxygen levels linked to the patent foramen ovale.

Closure of a patent foramen ovale to prevent migraines isn’t currently recommended. Closure of a patent foramen ovale to prevent a stroke remains controversial.

In some cases, doctors may recommend closure of the patent foramen ovale in individuals who have had recurrent strokes despite medical therapy, when no other cause has been found.

PFO repair

Procedures to close a patent foramen ovale include:

Device closure

Using cardiac catheterization, doctors can insert a device that plugs the PFO. In this procedure, the device is on the end of a long flexible tube (catheter).

The doctor inserts the device-tipped catheter into a vein in the groin and guides the device into place with the imaging assistance of an echocardiogram.

Device closure is safe and seems to be effective, with a stroke recurrence rate of between 0% and 3.8% per year ¹. The functional closure is usually followed by permanent fusion of the 2 flaps comprising the defective atrial septum. Complete closure occurs in up to 80%, and in an additional 10% to 15% the residual right-to-left shunting appears to be trivial ¹.

Although complications are uncommon with the device closure procedure, a tear of the heart or blood vessels, dislodgement of the device, or the development of irregular heartbeats may occur. Atrial arrhythmias may occur in 3% to 5% but are transient. Although the rate of development of atrial fibrillation has been 5% to 6% with some devices, they have also been associated with thrombus formation on the device. Late cardiac perforation has been reported with some devices but appears to be rare. In comparisons, atrial fibrillation was more common among closure patients than anticoagulated patients in secondary preventive strategies ⁶.

Intraprocedural complications utilizing device closure include perforation resulting in tamponade, air embolism, device embolization, and stroke ¹. However, these are all rare events in experienced hands, with rates of less than 1% ¹.

PFO surgery

A surgeon can close the patent foramen ovale by opening up the heart and stitching shut the flap-like opening. This procedure can be conducted using a very small incision and may be performed using robotic techniques.

If you or your child is undergoing surgery to correct another heart problem, your doctor may recommend that you have the PFO corrected surgically at the same time. Research is ongoing to determine the benefits of closing the PFO during heart surgery to correct another problem.

Stroke prevention

PFO has been identified as the major contributing factor in cryptogenic stroke in 50% of affected young adults and is present in 25% of the general adult population.

Medications can be used to try to reduce the risk of blood clots crossing a PFO (patent foramen ovale). Antiplatelet therapy such as aspirin or clopidogrel (Plavix) and other blood thinning medications (anticoagulants) — such as warfarin (Coumadin, Jantoven), dabigatran (Pradaxa), apixaban (Eliquis) and rivaroxaban (Xarelto) — may be helpful for people with a patent foramen ovale who’ve had a stroke.

It’s not clear whether medications or procedures to close the defect are most appropriate for stroke prevention in people with a PFO (patent foramen ovale). Studies are ongoing to answer this question.

If you’ll be traveling long distances, it’s important to follow recommendations for preventing blood clots. If you’re traveling by car, stop periodically and go for a short walk. On an airplane, be sure to stay well-hydrated and walk around whenever it’s safe to do so.

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