Download Pro: An Incidental PFO Should Be Repaired When Discovered

Pro: An Incidental PFO Should Be Repaired When
Discovered During Planned OPCAB Surgery
Michelle Capdeville, M.D.
Associate Professor
Cleveland Clinic Lerner College of Medicine
PFO--WHAT IS IT?
The foramen ovale is bordered by the septum secundum (limbus of the fossa ovalis) and the septum
primum, which serves as a valve within the fossa ovalis, and allows blood to flow from the right atrium to
the left atrium. Normally, the foramen ovale closes functionally after birth, when lung expansion and
initiation of the pulmonary circulation reverses the pressure gradient between the atria. A PFO develops
when the atrial septum fails to seal with fibrous adhesions after birth (normally this fusion is complete by
1-2 years of age). This allows a potential shunt to be present, although the PFO generally remains closed by
the normally higher left atrial pressure. A PFO occurs in more than 25% of the U.S. population.
PFO--HOW COMMON IS IT?
The reported incidence of PFO is: 25% of normal healthy adults; 27.3% of autopsy specimens; 34.3% in
first 3 decades of life; 25.4% in the 4th-8th decades; and 20.2% in the 9th-10th decades. PFO prevalence
decreases with age in a linear fashion. This has led pathologists to interpret this as meaning there is late
closure of the PFO. Conversely, there may be a shortened longevity associated with PFO, thereby making
the incidence lower in the elderly. The size of a PFO increases with age, secondary to stretching of the
fossa ovalis (causing greater separation of the ostium secundum).
PFO--WHY DO WE CARE?
PFO can lead to two major adverse events: shunting of deoxygenated blood into the systemic circulation,
and paradoxical embolism of air or thrombus/fatty material. PFO has been linked to cryptogenic strokes.
Over 40% of all ischemic strokes have no well documented cause and are considered cryptogenic.
Approximately 50% of patients with cryptogenic stroke have a PFO. This is especially relevant in patients
< 55 years of age. Cases of hypoxemia in patients with a PFO or small ASD have been reported in the
presence of normal right atrial pressures and responded to percutaneous closure.
DIAGNOSIS OF PFO
Contrast TEE is considered to be the modality of choice for diagnosing PFO. A PFO is confirmed if
microbubbles appear in the left atrium within 3 cycles of complete opacification of the right atrium (to
differentiate from extracardiac/pulmonary shunts). Color flow Doppler using a low pulse repetition
frequency provides comparable and perhaps greater accuracy because it is not influenced by the presence of
a Eustachian valve. In the presence of a prominent Eustachian valve, blood injected from the lower
extremities (via the IVC) allows more passage of bubbles across a PFO compared to blood injected via an
upper extremity I.V. (i.e. improved sensity and specificity of the bubble test).
Under normal circumstances, left atrial pressure is greater than right atrial pressure. There is a brief
pressure reversal in early ventricular systole. During the release of a Valsalva maneuver or during
coughing, there is increased venous return to the heart, leading to transient elevation of right atrial pressure.
Coughing or inducing a Valsalva maneuver can increase the detection of a PFO that is not seen without
such provocation.
MORPHOLOGY OF PFO
PFO is characterized by: size (maximum separation of septum primum and septum secundum), presence of
atrial septal aneurysm (ASA), severity of shunting by contrast injection (mild, 3-9 microbubbles; moderate
10-30 microbubbles; severe > 30 microbubbles), prominence of Eustachian valve, presence of Chiari
network; tunnel length (maximum overlap of septum primum and septum secundum).
It has been shown that patients with CVAs had larger PFOs, longer tunnels, and a greater incidence of
ASA.
ATRIAL SEPTAL ANEURYSM
An atrial septal aneurysm (ASA) is made up of thin tissue in the region of the fossa ovalis that moves
rhythmically with the cardiac and respiratory cycles, protruding into and out of the atrial cavities. It is
frequently seen in association with a PFO. Paradoxical embolism is believed to be the likely mechanism of
embolic events in patients with ASA, although other potential mechanisms of cardioembolism have been
postulated, including thrombus formation within the ASA, supraventricular arrhythmias, and associated
mitral valve prolapse.
ROLE OF THE EUSTACHIAN VALVE
The Eustachian valve is the embryological remnant of the fetal sinus venosus valve. It can be seen as an
echo dense ridge-like or undulating structure at the junction of the IVC and right atrium. It is present in up
to 70% of patients who have a PFO. Persistence of the Eustachian valve may prevent spontaneous closure
of a PFO after birth by directing blood from the IVC to the interatrial septum. Eustachian valve thrombosis
has been described, and in the presence of a PFO can lead to paradoxical embolization.
ANATOMY VS. PATHOPHYSIOLOGY
Both anatomic and pathophysiologic variables contribute to stroke risk in patients with a PFO. Interatrial
pressure gradients play an important role in the development of stroke. The mechanisms behind the
etiology of cryptogenic stroke in patients with PFO are speculative at best. Anecdotal observation of large
thrombi migrating across a PFO has led to the assumption that embolization is the primary mechanism.
Others have suggested that smaller embolic material can form in situ within a PFO. The “tunnel” of the
PFO would thereby provide a procoagulant environment where there is stagnation.
EPIDEMIOLOGY OF STROKE
Stroke is the third leading cause of death in developed countries and a primary cause of long-term disability
and hospitalization. Eighty-eight percent of the 700,000 strokes that occur annually in the U.S. are of
ischemic etiology, and in more than 40% of cases of ischemic stroke, no clear source could be identified
(i.e. cryptogenic). There is a 40-56% incidence of PFO in patients with cryptogenic stroke. This is
especially true in patients less than 55 years old. When you add up the numbers, 98,000-139,000 strokes
could theoretically be due to PFO each year. A PFO can allow microemboli to traverse into the left heart
and enter the cerebral circulation. Deep vein thrombosis and clotting deficiencies can potentially increase
this risk.
Government statistics show that the mean lifetime cost of ischemic stroke is $140,000 per patient. In 2007,
stroke-related costs were expected to reach $62.7 billion dollars nationally.
DEEP VEIN THROMBOSIS
The incidence of deep vein thrombosis (DVT) in the general population is close to 1:5,000, and increases
with age. In some patients there is an underlying hypercoagulable disorder (e.g. antiphospholipid
syndrome, Factor S and C deficiency, factor V Leiden, Behcet’s disease, antithrombin III deficiency,
paroxysmal nocturnal hemoglobinuria).
In the presence of a PFO > 4 mm, patients with pulmonary embolism have a 10x risk of death and 5x risk
of systemic embolism compared to patients without a PFO.
PRECIPITATING FACTORS FOR SHUNTING WITH PFO
Conditions that lead to elevated right atrial pressure increase the risk of shunting and hypoxemia in the
presence of a PFO. Likewise, conditions that lower left atrial pressure can increase right-to-left shunting
across a PFO (this is particularly relevant in patients undergoing placement of a left ventricular assist
device). Conditions that alter or distort the normal anatomical relationships within the heart can result in
increased right-to-left shunting in the presence of a PFO. Finally, numerous conditions are associated with
elevated right atrial pressure: pulmonary embolism, adult respiratory distress syndrome (ARDS), severe
tricuspid regurgitation, hypoxic pulmonary vasoconstriction, right ventricular infarction, poor right
ventricular preservation during cardiopulmonary bypass, right-sided tamponade, severe COPD, obstructive
sleep apnea (OSA), Pickwickian syndrome, asthma, PEEP, and mechanical ventilation.
It has been shown in one study that patients with severe COPD have an increased prevalence of PFO, and
that approximately 50% of patients with severe COPD and PFO show significant oxygen desaturation
during a Valsalva maneuver.
During nocturnal apneic periods, patients with OSA develop transient elevations of right-sided pressures.
PEEP and the inspiratory phase of mechanical ventilation can lead to an increase in pulmonary vascular
resistance, and lead to a reversal of normal interatrial pressure gradients.
During sitting craniotomy for posterior fossa surgery, it is not uncommon for air to be entrained into the
venous system. Venous air embolism is a well recognized phenomenon with these types of procedures, and
can result in systemic air embolization in the presence of a PFO.
Long bone fractures and total joint arthroplasty can lead to paradoxical fat embolism in the presence of a
PFO.
Deep sea divers with a PFO are at greater risk for decompression sickness. During decompression, nitrogen
bubbles develop and become trapped in the pulmonary microvasculature, leading to an increase in
pulmonary artery pressure. This finding, along with a Valsalva maneuver, that is often done to equalize
middle ear pressure, can lead to gas embolization across the PFO. PFO can worsen hypoxemia in scuba
divers at great depths.
At high altitudes, PFO can lead to hypoxia secondary to hypoxic pulmonary vasoconstriction, leading to
elevated pulmonary artery pressures. Hypobaric decompression sickness has been described in high altitude
aviators and astronauts during extravehicular activity.
Platypnea-orthodeoxia syndrome is a rare condition that manifests as dyspnea (platypnea) and arterial
desaturation (orthodeoxia) occurring in the upright position, and relieved by assuming a recumbent
position. It was originally described in 1949, and has been associated with pneumonectomy, lobectomy,
COPD, cirrhosis, and ascending aortic aneurysm. Most cases have been described in patients with
previously asymptomatic interatrial shunts who underwent pneumonectomy. In particular, right
pneumonectomy can alter venous return to the right heart by distorting the relationship of the IVC to the
fossa ovalis, such that IVC blood is preferentially directed towards a PFO.
During migraine attacks, there is hyperaggregation of platelets. It has been suggested that
microembolization in the vertebrobasilar territory across a PFO causes migraine with aura in some
instances.
PFO may also be associated with arterial vascular occlusion to the retina and optic nerve.
Decreased left ventricular afterload with normal right atrial pressure has been described as leading to rightto-left interatrial shunting.
The concept of atrial vulnerability, which is based on effective refractory periods, atrial conduction time,
and inducible atrial fibrillation, is apparently frequent in patients with cryptogenic stroke (PFO, ASA, or
both). PFO and ASA have also been associated with an increased incidence of postoperative atrial
fibrillation following CABG.
SO, WHAT IF YOU HAVE A PFO AND…
Do a Valsalva maneuver?
Require PEEP during postoperative mechanical ventilation?
Have a THA complicated by fat embolism?
Sustain long bone fractures?
Undergo sitting craniotomy?
Have obstructive sleep apnea?
Have severe COPD?
Have transient global amnesia?
Develop a pulmonary embolism?
Scuba Dive?
Work in a compressed air tunnel?
Have a chronic cough?
Are a high altitude aviator? (HPV occurs at high altitude)
Are an astronaut engaging in extravehicular activity?
Use birth control pills and develop ATIII deficiency?
Develop tamponade following OPCAB?
TREATMENT OPTIONS FOR PFO
There are four: do nothing, anticoagulation with warfarin, antiplatelet therapy, and PFO closure (surgical or
percutaneous device)
WHAT WE DO KNOW ABOUT PFO CLOSURE
Between 1998 and 2004 the surgical volume for PFO closure has remained relatively stable, while
percutaneous closure has increased more than 50-fold. Antiplatelet and anticoagulant therapy (i.e. medical
management) have a significant failure rate for the prevention of recurrent stroke/TIA in patients with a
PFO.
In cryptogenic stroke patients, PFO closure does not guarantee freedom from recurrent neurological events
in the future. Furthermore, other stroke etiologies may come into play. One has to keep in mind, however,
that published studies lack consistency. Things to consider when reviewing and interpreting this literature
include:
Echocardiography: TTE or TEE? Biplane or multiplane? Contrast and color? Effect of Eustachian valve on
detection of PFO? Use of low pulse repetition frequency with color flow Doppler? Post-pump TEE done?
Provocative maneuvers?
Other risk factors for stroke: hypercoagulable state?
How often do we ask our patients about specific risk factors, such as their interest in scuba diving, or
whether their migraines are associated with aura?
CABG AND THE INCIDENTAL FINDING OF A PFO
Because intraoperative TEE is frequently used in cardiothoracic surgery (routinely in many institutions), it
goes without saying that incidental PFOs are being detected with greater frequency. The question that
remains to be answered is whether or not an incidental PFO should be closed. For open cardiac procedures,
PFO closure adds little to the operating time and does not alter cannulation strategy. Greater consideration
must be given when an off-pump strategy or a non-intracardiac operation (i.e. CABG, AVR) should be
altered to address a PFO. To date, there are no randomized trials that help to answer this question, so the
question that must be addressed is whether the benefit of closing an incidental PFO is greater than the risk
of leaving it alone. The other point that needs to be questioned is the rationale behind off-pump versus onpump CABG. Reasons for avoidance of cardiopulmonary bypass include patient characteristics (comorbidity, aortic atherosclerosis precluding aortic manipulation) and surgeon preference. By itself, PFO
closure is a relatively low risk procedure, and published studies report no mortality and little morbidity.
There have been several case reports describing patients with PFO who underwent uncomplicated onpump CABG that was complicated by worsening of right-to-left shunting in the postoperative period.
Clearly, any factor leading to worsening right ventricular function (infarction, pulmonary embolism, poor
myocardial preservation) can lead to an increase in right atrial pressure and increased shunting with
hypoxemia.
During off-pump CABG, cardiac manipulation/elevation can potentially lead to right-to-left shunting and
hypoxemia, which can be even more detrimental when the wide hemodynamic disturbances that can occur
are taken into consideration. A case has been reported where a patient underwent OPCAB (without
intraoperative TEE) and had to return to the OR for PFO closure for refractory hypoxemia.
We really don’t know the impact of a PFO on postoperative outcomes. Is the risk of placing a patient on
cardiopulmonary bypass for a short interval greater or less than the risk of developing a stroke in the short
or long term?
Things to consider when deciding on whether to change operative strategies from off-pump to on-pump in
order close a PFO include presence of:
Shunting without provocative maneuvers
History of TIA/stroke of unknown etiology
Atrial septal aneurysm
Elevated right-sided pressures
Pulmonary hypertension
Presence of a prominent Eustachian valve
Obstructive sleep apnea
Hypercoagulable state
Severe right ventricular dysfunction
History of migraine with aura
DVT or PE history
Activities associated with shunting from a PFO (scuba diving, flying, high altitude climbing)
We don’t know the actual incidence of perioperative PFO-related morbidity. It can also be difficult to
differentiate between individual causes of stroke and hypoxemia.
A large body of equivocal information comes from case reports, case series, and retrospective or
observational analyses. Until properly conducted randomized prospective studies are undertaken, the
answer to the question “What should be done when an incidental PFO is detected at the time of cardiac
operation?” will elude us. The escalating number of percutaneous device closures for PFO may hinder
matters further, because of unwillingness to randomize patients to a non-treatment group.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
American Heart Association Heart Disease and Stroke Statistics—2006 Update
(http:///www.americanheart.org/presenter)
Asirdizer M, Tatlisumak: The role of Eustachian valve and patent foramen ovale in sudden death.
Journal of Clinical and Forensic Medicine 2006;13:262-7.
Berthet K, Lavergne T, Cohen A, et al.: Significant association of atrial vulnerability with atrial
septal abnormalities in young patients with ischemic stroke of unknown cause. Stroke
2000;31:398-403.
Cabanes L, Coste J, Derumeaux G, et al.: Interobserver and intraobserver variability in detection
of patent foramen ovale and atrial septal aneurysm with transesophageal echocardiography. J Am
Soc Echocardiogr 2002;15:441-6.
Capdeville M, Yang SX: Utility of transesophageal echocardiography in the diagnosis of a
previously undetected atrial septal aneurysm with shunt. J Cardiothorac Vasc Anesth
2005;19:529-38.
Chaney MA: Patent foramen ovale and off-pump coronary artery bypass graft surgery. SCA
Newsletter, October 2002.
Chidambaram M, Mink S, Sharma S: Atrial septal aneurysm with right-to-left interatrial shunting.
Tex Heart Inst J 2003;30:68-70.
Dearani JA, Ugurlu BS, Danielson GK, et al.: Surgical patent foramen ovale closure for
prevention of paradoxical embolism-related cerebrovascular ischemic events. Circulation
1999;100:II171-5.
Desai AJ, Fuller CJ, Jesurum JT, Reisman M: Patent fopramen ovale and cerebrovascular
diseases. Nature Clinical Practice 2006;3:446-55.
Djaiani G, Phillips-Bute B, Podgoreanu M, et al.: The association of patent foramen ovale and
atrial fibrillation after coronary artery bypass graft surgery. Anesth Analg 2004;98:585-9.
Fowkes FJ, Price JF, Fowkes FG: Incidence of diagnosed deep vein thrombosis in the general
population: Systematic review. Eur J Vasc Surg 2003;25:1-5.
Frumento RJ, OZ MC, Bennett-Guerrero E: National survey regarding management of an
intraoperatively diagnosed patent foramen ovale during coronary artery bypass graft surgery. J
Cardiothorac Vasc Anesth 2005;19:150-4
Gersony DR, Kim SH, DiTullio M, et al.: Acute myocardial infarction caused by paradoxical
coronary embolization in a patient with a patent foramen ovale. J Am Soc Echocardiogr
2001;14:1227-9.
Godart F, Rey C, Prat A, et al.: Atrial right-to-left shunting causes severe hypoxaemia despite
normal right-sided pressures: Report of 11 consecutive cases corrected by percutaneous closure.
Eur Heart J 2000;21:483-9.
Goel SS, Tuzcu EM, Shishebor MH, et al.: Morphology of the patent foramen ovale in
asymptomatic versus symptomatic (stroke or transient ischemic attack) patients. Am J Cardiol
2009;103:124-9.
Hagen PT, Scholz DG, Edwards WD: Incidence and size of patent foramen ovale during the first
10 decades of life: An autopsy study of 965 normal hearts. Mayo Clin Proc 1984;59:17-20.
Homma S, Di Tullio MR, Sacco RL, et al.: Surgical closure of patent foramen ovale in
cryptogenic stroke patients. Stroke 1997;28:2376-81.
Jaffe RA, Pinto FJ, Schnittger I, Brock-Utne JG: Intraoperative ventilator-induced right-to-left
intracardiac shunt. Anesthesiology 1991;75:153-5.
Kerut EK, Norfleet WT, Plotnick GD, Giles TD: Patent foramen ovale: A review of associated
conditions and the impact of physiological size. J Am Coll Cardiol 2001;38:613-23.
Kessel-Shaefer A, Lefkovits M, Pfisterer ME, Buser P: Migrating thrombus trapped in patent
foramen ovale. Circulation 2001;203:1928.
Lechat P et al.: Prevalence of patent foramen ovale in patients with stroke. N Engl J Med
1988;318:1148-52.
Levine BD, Grayburn PA< Voyles WF, et al.: Intracardiac shunting across a patent foramen ovale
may exacerbate hypoxemia in high-altitude pulmonary edema. Ann Intern Med 1991;114:569-70.
23. Landzberg MJ, Khairy P: Indications for the closure of patent foramen ovale. Heart 2004;90:21924.
24. Nootens MT, Berarducci LA, Kaufmann E, et al.: The prevalence and significance of patent
foramen ovale in pulmonary hypertension. Chest 1993;104:1673-5.
25. Opotowsky AR, Landzberg MJ, Kimmel SE, Webb GD: Trends in the use of percutaneous closure
of patent foramen ovale and atrial septal defect in adults, 1998-2004. JAMA 2008;299:521-2.
26. Overell JR, et al.: Interatrial septal abnormalities and stroke: A meta-analysis of case-control
studies. Neurology 2000;55:1172-9.
27. Roxas-Timonera M, Larracas C, Gersony D, et al.: Patent foramen ovale presenting as platypneaorthodeoxia: Diagnosis by transesophageal echocardiography. J Am Soc Echocardiogr
2001;14:1039-41.
28. Ruchat P, Bogousslavsky, Hurni M, et al.: Systematic surgical closure of patent foramen ovale in
selected patients with cerebrovascular events due to paradoxical embolism. Early results of a
preliminary study. Eur J Cardiothorac Surg 1997;11:824-7.
29. Sandifer DP, Gonzalez JL: Refractory hypoxemia associated with regional cardiac tamponade and
patent foramen ovale. Crit Care Med 1997;25:1608-11.
30. Schneider B, Zienkiewicz T, Jansen V, et al.: Diagnosis of patent foramen ovale by
transesophageal echocardiography and correlation with autopsy findings. Am J Cardiol
1996;77:1202-9.
31. Schuchlenz HW, Weihs W, Hackl E, Rehak P: A large Eustachian valve is a confounder of
contrast but not of color Doppler transesophageal echocardiography in detecting a right-to-left
shunt across a patent foramen ovale. Int J Cardiol 2007;117:138-9.
32. Schuchlenz HW, Saurer G, Weihs W, Rehak P: Persisting eustachian valve in adults: Relation to
patent foramen ovale by transesophageal echocardiography and cerebrovascular events. J Am Soc
Echocardiogr 2004;17:231-3.
33. Shanoudy H, Soliman A, Raggi P, et al.: Prevalence of patent foramen ovale and its contribution
to hypoxemia in patients with obstructive sleep apnea. Chest 1998;113:91-2.
34. Soliman A, Shanoudy H, Liu J, et al.: Increased prevalence of patent foramen ovale in patients
with severe chronic obstructive pulmonary disease. Chest 1999;12:99-105.
35. SukernikMR, Mets B, Bennett-Guerrero E: Patent foramen ovale and its significance in the
perioperative period. Anesth Analg 2001;93:1137-46
36. Sukernik MR, Mets B, Kachulis B, Oz MC, Bennett-Guerrero E: The impact of newly diagnosed
patent foramen ovale in patients undergoing off-pump coronary artery bypass grafting: Case series
of eleven patients. Anesth Analg 2002;95:1142-6.
37. Sukernik MR, Bennett-Guerrero: The incidental finding of a patent foramen ovale during cardiac
surgery: Should it always be repaired? A core review. Anesth Analg 2007;105:602-10.
38. Tabry I: Patent foramen ovale causing refractory hypoxemia after off-pump coronary artery
bypass: A case report. Heart Surgery Forum #2003-90953Sukernik MR, Sumeet G,
39. Webster MW et al.: Patent foramen ovale in young stroke patients. Lancet 1988;2:11-2.