Sixty-Eight-Year-Old Woman With Intermittent Hypoxemia
A 68-year-old woman presented on September 30, 1994, with shortness of breath, nonproductive cough, and retrosternal chest tightness radiating to the neck. She believed her symptoms correlated with exposure to an unknown inhalant earlier that day, while she sat in her ophthalmologist’s office. Eleven other patients and two ophthalmologists in the same clinic were exposed to the same “toxic inhalant” and reported similar symptoms including burning eyes. All were transported to the hospital for evaluation, and all but this patient were discharged from the emergency department in good condition.
The patient initially improved in the emergency department while lying supine with an O2 saturation of 97% on 2 L/min O2 by nasal cannula. However, when she stood up to make a telephone call, she noted acute increase in dyspnea, and her O2 saturation fell to the low 80s and was minimally corrected with increased oxygen supplementation. Consequently, she was admitted to the intensive care unit for further evaluation and treatment.
She had had one previous episode of prolonged shortness of breath and fatigue approximately 3 months earlier while raking leaves in the hot summer sun. She attributed her symptoms to the heat. Otherwise, she had been fairly active at home, was able to perform daily chores without dyspnea or chest pain, denied paroxysmal nocturnal dyspnea or orthopnea, and noted only mild swelling of her ankles occasionally. She had no dyspnea or cyanotic spells during childhood and had tolerated two pregnancies without difficulty. She denied hemoptysis or pleuritic chest pain, had smoked five to six cigarettes per day for several years, and had used alcohol occasionally. A routine yearly stress test had been performed recently and was reported as normal.
Her past medical history was significant for treated systemic hypertension, osteoporosis with resultant kyphosis, bilateral varicosities of the lower extremities (varicose vein stripping in 1992), and recurrent pain and swelling of the left lower extremity (venogram in January 1994 was negative for deep vein thrombosis). Her current medications included diltiazem, calcium supplementation, and a nonsteroidal anti-inflammatory agent as needed for lower-extremity pain.
On physical examination, the patient was alert and able to converse while lying flat despite tachypnea. Her temperature was 98°F; pulse, 98 and regular; and respirations, 22 per minute. Blood pressure was 150/90 mm Hg and did not change with positioning. Oxygen saturation on room air was 85%. There was no jugular venous distention, and carotid pulses were full without bruits.
The point of maximal cardiac impulse was in the fifth intercostal space at the midclavicular line. The rhythm was regular with a normal S1, normal physiological splitting of S2, normal P2 component, and an S4. A 2/6 holosystolic murmur was evident at the left lower sternal border with radiation to the apex and axilla. The lungs were clear to auscultation. The abdomen was soft and nontender with normal bowel sounds and no hepatosplenomegaly. There was slight edema (left>right) and mild cyanosis but no clubbing of the digits. The femoral pulses were normal without bruits. Her dorsalis pedis and pretibialis pulses were 1+ bilaterally.
The laboratory values on admission appear in Table 1⇓. The electrocardiogram showed normal sinus rhythm, an axis of −30°, and nonspecific ST-segment and T-wave changes.
The patient was admitted to the intensive care unit on external oxygen supplementation. During the next 2 weeks, she continued to experience intermittently worse hypoxemia. Improved oxygenation appeared to correlate with being in the supine position; however, this was not consistent. She required oxygen supplementation in varying degrees. At times, she would have adequate oxygen saturation on 2 L per minute O2 by nasal cannula, and at other times she experienced prolonged hypoxemia on 100% O2 by nonrebreather face mask. One episode of hypoxemia was recorded at po2 of 49 mm Hg on 2 L per minute O2 by nasal cannula and required initiation of continuous positive airway pressure of 15 L at 10 cm H2O.
Doppler examination of the lower extremities was negative for deep vein thrombosis. Cardiac catheterization showed normal right- and left-sided pressures, normal coronary arteries, and no significant shunt by angiography. Arterial saturation during the catheterization was 95% on room air. However, after the procedure, intermittent hypoxemia continued. Consequently, the patient underwent a diagnostic procedure and further therapy.
Phebe Chen, MD
Admission chest radiograph showed slight cardiomegaly, atherosclerotic changes of the aorta, and mild emphysematous changes of the lungs (Fig 1⇓). A V-Q lung scan showed low probability for pulmonary embolism; there was, however, increased uptake of radioactive material in the liver, kidneys, and brain suggesting a right-to-left shunt (Fig 2⇓). A pulmonary angiogram showed no evidence of emboli or arteriovenous malformations.
Wayne Dear, MD
This 68-year-old woman presented to the emergency department with 13 other adults after exposure to noxious fumes. The others recovered quickly and were released. This patient, however, was observed to become short of breath when standing and demonstrated coincident arterial blood oxygen desaturation. She was known to have long-term venous insufficiency with persistent leg discomfort and mild edema despite previous bilateral vein strippings. Previous venography had provided no evidence of deep venous thrombosis. Her heart rate, blood pressure, and temperature were normal, but she was tachypneic and cyanotic without clubbing. The jugular venous pressure was normal and the lungs were clear on both physical examination and chest x-ray. The cardiac examination was normal except for a fourth heart sound and a moderate systolic murmur most prominent at the lower left sternal border with audible radiation to the apex and left axilla; no respiratory variation was noted. The ECG simply showed nonspecific ST-T–wave changes and no evidence of an acute inferior wall myocardial infarction. Initial laboratory data were normal except for arterial blood gas oxygen saturations of 47 and 52 mm Hg obtained during her first observed episode. During hospitalization, she repeatedly demonstrated dyspnea and cyanosis when standing, with recovery when supine. It is not stated whether she was observed to have a decubitus preference (trepopnea).
At cardiac catheterization, hemodynamics were reported as normal, without evidence of significant intracardiac shunts. Indeed, the systemic arterial blood oxygen saturation was reported to be 95%. Pulmonary angiography and coronary arteriography were essentially normal. Doppler study detected no thrombi in the deep veins of the lower extremities, and a V-Q scan was low probability for pulmonary emboli.
There is neither a pulmonary nor a hematologic basis for the patient’s episodes of cyanosis. Therefore, these events must be based on an intermittent intracardiac right-to-left shunt. The most reasonable explanation is a PFO. This embryological remnant is present in 25% to 30% of adults.1 The anatomy of a PFO allows it to open when right atrial pressure exceeds that in the left atrium; the potential orifice can range from a few millimeters to 2 cm in diameter.2 Typical causes for systemic arterial oxygen desaturation secondary to right-to-left shunting through a PFO include pulmonary emboli, right ventricular infarction, and obstruction of the tricuspid valve.
This woman’s cyanosis when standing and relief when supine must also be reasonably explained. The most tempting hypothesis is a mobile obstruction in the right atrium, which could intermittently impair tricuspid valve flow. A pedunculated right atrial myxoma would certainly be a most attractive explanation, because such a mass could abruptly obstruct the tricuspid valve and produce the reversed atrial pressure gradient necessary for right-to-left shunting.
Slower recovery after lying down may relate to transient elevation of pulmonary artery pressure in response to the hypoxemia. Her nondescript heart murmur could be associated with trauma to the tricuspid valve from a right atrial tumor. Coates and Drake3 reported a similar case of an intermittently cyanotic 50-year-old patient with such a tumor. Several other similar cases have subsequently been reported.4
Contrast echocardiography will be useful in demonstrating the PFO and perhaps even a right atrial tumor.
Eddy Barasch, MD
A transthoracic echocardiographic-Doppler examination was performed shortly after the patient’s admission. The cardiac chambers were not enlarged. Both ventricles had normal wall thickness and normal systolic and diastolic function. The coronary sinus was not enlarged. Aortic root and ascending aorta were dilated (4.5 cm). Thickening of the mitral valve with bileaflet prolapse and mild to moderate mitral regurgitation were noted. Doppler interrogation of the other three valves was normal. The calculated pulmonary artery systolic pressure was 34 mm Hg. Agitated 0.9% saline (10 mL) injected into a peripheral vein demonstrated immediate opacification of the left atrium. A TEE, performed with a biplane 5-MHz probe, followed the transthoracic study to get a better visualization of the interatrial septum and to identify the distal end of all four pulmonic veins. Examination of the interatrial septum revealed normal septal thickness and a PFO with a maximal diameter of 1 cm (Fig 3⇓). Color Doppler, pulse-wave Doppler, and a contrast study with agitated saline during quiet respiration demonstrated a right-to-left shunt across the PFO (Fig 4⇓). The confluence of all four pulmonic veins with the left atrium was identified. Agitated 0.9% saline (10 mL) was injected into the left and right cephalic veins and into the right femoral vein to exclude any possible connection between superior or inferior vena cava and left atrium. No such connections were demonstrated. A final contrast bolus was injected into the main pulmonary artery through the pulmonary artery lumen of a Swan-Ganz catheter to identify the presence of pulmonary vascular malformations. These were excluded as well.
TEE is the most accurate tool for detecting a PFO.5 The presence of a large PFO may also be identified by two-dimensional echocardiography. The timing and magnitude of the right-to-left shunt across the interatrial septum are assessed with color Doppler, pulse Doppler, and contrast study during quiet respiration or during maneuvers that increase venous return for a brief period of time (eg, release from Valsalva maneuver or cough), with subsequent augmentation of physiological end-systolic right-to-left atrial pressure gradient.6 Color Doppler is a very sensitive method for evaluating a PFO, and contrast echocardiography provides confirmatory information. The microbubbles injected into a peripheral vein are trapped in the pulmonary capillary network or shrink and disappear by diffusion.7 In the presence of an intact interatrial septum and normal pulmonary vasculature, not a single bubble should appear in the left atrium when a contrast agent is injected into a peripheral vein. In the presence of a PFO, the appearance of microbubbles in the left atrium will be seen within the first two to three cardiac cycles after right atrial appearance; their later appearance raises the possibility of pulmonary vascular malformations. A semiquantitative method of evaluating the degree of shunt has been proposed recently.8 9 It consists of counting the maximal number of microbubbles seen in the left atrium after injection of contrast material into a peripheral vein. Numbers greater than 20 or 50 microbubbles suggest large shunts.
In our patient, a large PFO was diagnosed as the only intracardiac abnormality that could explain hypoxemia despite normal right heart pressures. The immediate surgical result was assessed by intraoperative TEE, which proved the successful closure of the PFO.
H. Vernon Anderson, MD, and Annie T. Varughese, MD
Right heart pressures and saturations were measured by means of a fluid-filled Swan-Ganz catheter with transducer setting of zero at the midchest. Left heart pressures and saturation were measured with a pigtail catheter placed in the left ventricle. Attempts to cross the interatrial septum with a Berman angiographic catheter were fruitless; thus, left atrial saturation was not obtained. The data appear in Table 2⇓. Due to technical difficulties, a precise pulmonary capillary wedge saturation was not obtained, and thus QP/QS was not calculated. Angiography with a Berman angiographic catheter at the atrial level revealed a mild right-to-left shunt. A prominent coronary vein was noted on injection of the right atrium. Pulmonary artery angiography showed normal pulmonary veins, and no arteriovenous malformations were appreciated. Coronary angiography revealed no significant abnormalities. Left ventricular ejection fraction was 47% with mild anterolateral and inferobasal hypokinesis.
The data obtained at cardiac catheterization reiterated previous findings of a right-to-left shunt and localized it at the atrial level. The data also confirmed normal right and left heart pressures and clarified the coronary artery status as being essentially normal. The patient’s working diagnosis was a PFO with intermittent hypoxemia but no significant postural component (with arterial blood gas sampling in the supine and sitting positions not significantly different). Because cardiac catheterization did not answer the question as to a vena cava to left atrium connection (by saturation sampling of the high superior vena cava), a repeat TEE was performed that excluded this possibility.
Michael Macris, MD
The patient was explored via median sternotomy. External appearance of the heart was remarkable for the presence of an unusually thin and dilated aortic root that measured 5 cm at maximum diameter. The wall of the right atrium was also exceptionally thin, suggesting a connective tissue disorder. The remainder of the heart appeared outwardly normal.
Following institution of total cardiopulmonary bypass by bicaval cannulation, the heart was arrested by use of cardioplegic solution. The right atrium was explored via standard lateral atriotomy. A large PFO was found, measuring 2 cm in diameter (Fig 5⇓). The edges of the septum primum were very thick and smooth, as would be expected in a long-standing defect. There were no findings to suggest any recent change in this atrial septal defect, such as rupture of part of the septum or the formation of any vegetations. Also of note, the remainder of the septum appeared normal as did the coronary sinus and the tricuspid valve. Exploration of the left atrium through the large PFO revealed normal pulmonary venous drainage and a normal mitral valve.
Repair of the defect was performed with a patch of knitted Dacron. The patch was used rather than primary closure because of the large size of the defect. There are reports that long-term follow-up of patients in whom primary repair was used indicates a higher incidence of dehiscence of the repair, as well as possibly greater incidence of arrhythmias.10
To complete the operation, the right atriotomy was repaired, the cross clamp released, and the heart revived. Residual air was removed from the heart by standard measures. TEE was repeated, indicating complete closure of the shunt. The patient was then easily weaned from cardiopulmonary bypass.
Postoperatively, the patient had a transient episode of profound hypoxia, with the Po2 dropping to 60 mm Hg on an Fio2 of 1.0. The TEE was repeated because of concerns about recurrent right-to-left shunting, but there was only a trivial amount of air bubble contrast seen passing through the interstices of the patch material, which is to be expected. The material requires about 2 days to seal completely. In retrospect, the hypoxia was most likely due to a transfusion reaction, as it resolved spontaneously and did not recur.
Subsequently, the patient gradually recovered. She was weaned from the ventilator to room air and then discharged. I last saw her about 1 month after surgery, and she was doing well.
H. Vernon Anderson, MD
Although patency of the foramen ovale can be shown to have been present in approximately one quarter of otherwise “normal” adult hearts at autopsy,1 in most cases the patency is undetected and not associated with clinical events during life. Patency, when it exists, probably is transient. The left atrial pressure normally remains greater than the right atrial pressure, and this pressure differential keeps the membrane of the foramen ovale pressed against the muscular interatrial septum. Shunting either left to right or right to left is prevented most of the time. However, a right-to-left shunt on contrast echocardiography has been described in healthy adults as well as in patients with surgically proven absence of an atrial septal defect.11 This generally small-magnitude shunt has been ascribed to the presence of a PFO. Transient reversal of the atrial pressure differential during the normal cardiac cycle, combined with spontaneous or provoked respiratory maneuvers that increase right atrial pressure, such as the Valsalva maneuver, may open the foramen ovale and create the right-to-left shunting.12 13 It is this shunting that has been associated with paradoxical systemic emboli, including such clinically significant events as stroke, transient cerebral ischemia, and peripheral embolization. While the existence of acute or chronically elevated right heart pressures—as with large pulmonary emboli, chronic lung diseases, or right ventricular failure—may be associated with increased shunting through a PFO and thereby with an increased risk of paradoxical emboli, this need not be the case. Any unexplained clinical events that raise the suspicion of embolic phenomena should prompt consideration of a cardiac source, including the possibility of a PFO. TEE appears to be superior to transthoracic echocardiography for delineation of the interatrial septum and for documentation of the shunt. In our case, the intermittent right-to-left shunting occurred in the absence of demonstrable pulmonary or systemic emboli.
Isolated PFO with intermittent right-to-left shunting.
Selected Abbreviations and Acronyms
|PFO||=||patent foramen ovale|
|QP/QS||=||pulmonary flow/systemic flow|
This clinicopathological conference was presented at The University of Texas Medical School at Houston on November 21, 1994.
1 Selected abbreviations and acronyms are defined on the next page.
- Copyright © 1995 by American Heart Association
Thompson T, Evans W. Paradoxical embolism. Q J Med. 1930;23:135-150.
Coates EO Jr, Drake EH. Myxoma of the right atrium, with variable right-to-left shunt: clinical and physiologic observations and report of a case with successful operative removal. N Engl J Med. 1958;259:165.
Soulié P, Acar J, Renault P, Lainée R. Azoulay. Les myxomes de l’oreillete dnoite. Arch Mal Coeur. 1961;54:241.
Sone D, Godard J, Hawke MW, Correti MC, Kittner S, Price T, Plotnick GD. Patent foramen ovale: the degree of shunting by contrast echocardiography predicts future events. Circulation. 1994;90(Pt 2):I-237.
Job FP, Ringelstein EB, Grafen Y, Fachskapf FA, Doberty C, Stockmanns A, Hanrath P. Comparison of transcranial contrast Doppler sonography and transesophageal contrast echocardiography for the detection of patent foramen ovale in young stroke patients. Am J Cardiol. 1994;74:381-384.
Cooley, DA. Techniques in Cardiac Surgery. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1984:108.