The Contribution of Aerospace Medicine Specialty Expertise in the Diagnosis and Treatment of Headache Disorders with Concomitant Clinically Symptomatic Dyscapnia (Respiratory Alkalosis/Acidosis).
A subset of patients with headache disorders presents with a dyscapnic state typically clinically symptomatic chronic respiratory alkalosis (CSCRA). CSCRA is well described as an important factor in increased neuromuscular irritability and reduces tissue oxygen delivery through reduction of cerebral blood flow (vasospasm) and left shift of the oxygen-hemoglobin dissociation curve, as well as increasing metabolic tissue oxygen demand all thought to be important factors in headache disorders. Novel testing paradigms that allow assessment of hypoxemia / orthodeoxia-platypnea include hypoxic echocardiography with bubble contrast to diagnose clinically significant right to left shunts (RLS). RLS (commonly through a patent foramen ovale (PFO)) is associated with migraine, particularly migraine with aura. We evaluate patients with an in-depth acid base analysis (including arterial blood gas analysis, comprehensive metabolic profile and urinalysis) and then pursue diagnostic evaluation of potential causative factors. Common causes of CSCRA include sleep disordered breathing, RLS (anatomic and capillary shunting), post-concussive states as well as post-viral or postoperative derangements of acid base status and associated with altered autonomic function. A focused diagnostic approach to discern the root cause for CSCRA may uncover treatable causes such as hypoxemia secondary to RLS or lung disease, sleep disorders and diaphragmatic dysfunction. The time-limited intervention with carbonic anhydrase to normalize acid base status and tissue carbon dioxide stores, as well as rehabilitation measures to normalize breathing patterns serve to normalize the acid base status, reduce neuromuscular irritability and reduce symptoms including headache.
- Research Article
- 10.3760/cma.j.issn.1006-7876.2018.01.009
- Jan 8, 2018
Objective To investigate the effect of the transcatheter closure of patent foramen ovale (PFO) on the treatment of migraine. Methods This prospective clinical trial enrolled 43 consecutive migraine patients with PFO from Department of Neurology, Beijing Anzhen Hospital from March 2014 to March 2015, in which PFO was diagnosed by transesophageal echocardiography (TEE) and contrast-enhanced transcranial Doppler (c-TCD). We grouped subjects according to their selection or refusal of PFO closure. Nine patients were allocated to treatment with PFO closure. Thirty-four patients were given with medical treatment and were assigned to control group. Basal clinical data, frequency of migraine, duration of migraine and scores of Headache Impact Test-6 (HIT-6) were collected. c-TCD was performed after procedure of PFO closure transthoracic echocardiography. Changes of HIT-6 scores were analyzed after closure of PFO in the follow-up period. Results Successful PFO procedure was achieved in all patients without any complications both in hospital and in follow-up period. Only one patient had residual Ⅱ-grade right-to-left shunt (RLS) tested by c-TCD. Mean scores of HIT-6 in the surgical group were reduced significantly (49.3±3.6 vs 67.5±4.9, t=15.129, P=0.000). There were statistically significant differences in mean reduction of HIT-6 scores in the following one year for the female (48.8±3.1 vs 69.8±2.6, t=15.674, P=0.002), constant RLS (47.8±2.1 vs 67.9±3.5, t=8.572, P=0.043), RLS Ⅲ (50.6±2.3 vs 65.4±2.7, t=7.663, P=0.039)/ RLS Ⅳ(48.2±1.9 vs 68.5±3.9, t=8.924, P=0.028)as well as migraine with aura subgroup (47.9±1.6 vs 68.3±3.8, t=13.532, P=0.001). Conclusion Our results suggest that transcatheter PFO closure is a safe and effective approach for the treatment of migraine, especially for female migraineur with aura and with constant serious RLS. Key words: Migraine; Patent foramen ovale; Septal occluder device
- Research Article
- 10.1161/str.50.suppl_1.wp261
- Feb 1, 2019
- Stroke
Introduction: Recent patent foramen ovale (PFO) closure trials have demonstrated efficacy in secondary stroke prevention. Transcranial Doppler (TCD) can reliably detect the presence of PFO, with sensitivity comparable to echocardiography. We sought to compare the sensitivity of TCD in detecting right to left shunt (RLS) using transesophageal echocardiogram (TEE) criteria as described in the CLOSE and REDUCE trials. Methods: We retrospectively reviewed all TCD studies at our institution who also had TEE studies. We excluded patients who had their PFO closed prior to one of these studies being performed. We classified the size of the PFO based on both REDUCE and CLOSE criteria (large was defined as greater than 25 microbubbles and greater than 30 microbubbles, respectively) and compared to the size based on the Spencer grade. Results: A total of 525 TCD bubble studies were performed at our institution from May 2013 to June 2018, 220 of which also underwent TEE. Using TEE as the gold standard, TCD detected 97.61% (41/42) of any moderate-large RLS and 100% (10/10) of any large RLS. The single patient who had a moderate RLS on TEE, but not TCD had a poor Valsalva during the TCD study. TCD detected 33 patients with RLS not detected on TEE [33% (33/100)], 33.3% of which were considered significant (Spencer grades 3-5). Conclusion: TCD is comparable to TEE in detecting moderate-to-large RLS based on REDUCE/CLOSE criteria. TCD detected an appreciable amount of RLS (a third of which were Spencer grades 3-5) not detected by TEE. Further study is needed to clarify the role of PFO closure in patients with significant RLS on TCD, but no RLS on TEE. TCD is a good alternative screening tool for RLS as compared with TEE methods from recent positive trials.
- Research Article
86
- 10.1016/j.jstrokecerebrovasdis.2008.12.001
- Aug 28, 2009
- Journal of Stroke and Cerebrovascular Diseases
Transcranial Doppler and Transesophageal Echocardiography: Comparison of Both Techniques and Prospective Clinical Relevance of Transcranial Doppler in Patent Foramen Ovale Detection
- Research Article
27
- 10.1111/echo.12403
- Oct 18, 2013
- Echocardiography
Although the "3 beat rule" is widely utiized to discriminate patent foramen ovale (PFO)-mediated right-to-left shunt (RTLS) from intrapulmonary RTLS using saline contrast transthoracic echocardiography (SCE), SCE diagnostic performance has yet to be validated using an invasive intracardiac standard. Percutaneous PFO occluder placement was recently shown to ameliorate hypoxia in patients with suspected PFO-mediated RTLS. We evaluated the ability of SCE to predict PFO presence and size using intracardiac echocardiography (ICE) as a gold standard in a hypoxic cohort. Sixty-three hypoxic patients with suspected PFO-mediated RTLS who underwent SCE at rest, with Valsalva maneuver, and with cough prior to ICE were evaluated retrospectively. PFO RTLS was defined by ICE findings including PFO anatomy, RTLS by saline contrast and color Doppler, and probe patency. SCE shunt severity and timing of left heart saline target appearance were compared to the presence of ICE-defined PFO RTLS. Forty-seven patients (75%) met criteria for PFO-mediated RTLS. A 4 beat cutoff for resting SCE provided optimal diagnostic performance for detection of PFO-mediated RTLS with a 71% sensitivity, 94% specificity, and 97% positive predictive value (PPV). Valsalva and cough maneuvers improved sensitivity compared to rest SCE (89% and 80%, respectively). Valsalva SCE shunt severity more accurately predicted PFO size than resting SCE. In contrast to the widely accepted "3 beat rule," resting SCE for the detection of PFO RTLS in a hypoxic population performs optimally using a 4-cycle cutoff with both excellent specificity and PPV.
- Research Article
15
- 10.1097/md.0000000000024175
- Jan 29, 2021
- Medicine
Background:Right-to left shunt (RLS) is regarded as a risk factor resulting in migraine, but the relevance between the RLS and migraine remains controversial. This paper aims at investigating the prevalence and RLS grade of patent foramen ovale (PFO) in cases of migraine (including migraine with and without aura) and evaluate the relationship between PFO and migraine.Methods:Synchronous test of contrast transthoracic echocardiography and contrast transcranial Doppler ultrasonography was performed in 251 cases of migraine, which contains 62 cases of migraine with aura (MA) and 189 cases without aura (MO) and 275 healthy adults. Among these cases, 25 cases with migraine and 14 healthy adults were evaluated through transesophageal echocardiography.Results:(1). The prevalence of permanent RLS, total RLS, and large RLS in migraine was 11.16%, 39.04%, and 17.13%, respectively, which was significantly higher than that of the controls (P = .042, <.001, and.001, respectively). (2). Permanent RLS was detected as 7.93% of the cases in MO, 20.96% in MA, and 6.18% in controls. Total RLS was detected as 35.98% of the cases in MO, 48.38% in MA, and 23.64% in controls. Large RLS was detected as 13.76% of the cases in MO, 27.41% in MA, and 7.27% in controls. Compared with controls, the positive rate of total RLS and large RLS in MO increased (P = .004 and.022, respectively), the that of permanent RLS, total RLS, and large RLS in MA also increased (P < .001 for each of the comparisons). The positive rate of permanent RLS and large RLS in MA was remarkably higher than that in MO (P = .005 and.013, respectively). (3) The presence of large-size PFO (≥2.0 mm) of migraine showed higher than that of the controls (P = .048).Conclusions:PFO is associated with the migraine (especially with aura), when it is permanent RLS, large RLS, and large-size PFO (≥2.0 mm).
- Research Article
4
- 10.1186/s40001-022-00855-0
- Nov 3, 2022
- European Journal of Medical Research
PurposeThe purpose of this study was to observe the morphologic characteristics of patent foramen ovale (PFO) by transesophageal echocardiography (TEE), and to analyze its correlation with right-to-left shunt (RLS) of contrast-transthoracic echocardiography (c-TTE) and contrast-transcranial Doppler ultrasonography (c-TCD).Methods124 patients with PFO were divided into four groups according to the morphological characteristics of PFO. RLS grade of each group PFO with c-TTE and c-TCD in resting and Valsalva manoeuvre was measured. Anatomical structures influencing RLS grade were analyzed statistically through multivariate logistic analyses and predictive models.ResultsThe 124 cases of PFO were divided into four groups: 55 cases (44.4%) with smooth uniform tubular tunnel (SUT), 21 cases (16.9%) with granule uniform tubular tunnel (GUT), 23 cases (18.5%) of right funnelform, 25 cases (20.2%) of left funnelform. Between group comparisons and multivariate logistic analyses revealed that PFO morphotype and interatrial septum(IAS) mobility were influencing factors of RLS degree. During Valsalva, the probability of c-TCD RLS ≥ 2 for the right funnelform PFO was 13.428 times that of the GUT, one unit increase in IAS mobility increased the probability of c-TCD RLS ≥ 2 by a factor of 2.029, model predicted c-TCD RLS ≥ 2 with 78.1% sensitivity and 94.7% specificity; During Valsalva, the probability of c-TCD RLS ≥ 2 for the SUT PFO was 4.244 times that of the GUT, one unit increase in IAS mobility increased the probability of c-TTE RLS ≥ 2 by a factor of 2.392, model predicted c-TTE RLS ≥ 2 with 80.2% sensitivity and 87.9% specificity.ConclusionsStudies have shown that the morphological structure of PFO is an influencing factor of RLS, and TEE can observe the specific morphological characteristics of PFO, which can further predict the level of RLS, help predict the occurrence of Cryptogenic stroke (CS). The above provides more evidences and surgical options for Interventional device closure indications.
- Research Article
1
- 10.1152/japplphysiol.00507.2012
- Jun 6, 2013
- Journal of Applied Physiology
A variation in right atrial and pulmonary arterial pressure might result in a shunt dynamic across a patent foramen ovale (PFO). In the present study we tested if peak exercise facilitates a restoration of right to left shunt (RLS) in stroke patients who demonstrated a functional PFO closure (no evidence of RLS across an initially demonstrated PFO). In stroke patients with PFO demonstrating a functional closure, the RLS was reassessed on peak exercise using contrast-enhanced transcranial Doppler sonography. The exercise procedure consisted of a cardiopulmonary exercise test with supplementary stress echocardiography for assessment of pulmonary circulation. Four stroke patients with initially PFO curtain pattern and a subsequent functional PFO closure (no evidence for RLS) underwent the procedure. In all four patients a RLS could be resurrected during peak physical exercise after a Valsalva strain. While in two patients peak exercise led to an RLS in a countable range of microembolic signals, in two patients a curtain pattern was obtained. One patient showed evidence for reoccurrence of RLS on peak exercise without a Valsalva strain. The patients with curtain pattern had a better peak exercise performance. Although the systolic pulmonary arterial pressure increased during exercise in all patients, there was no direct correlation with the detected RLS. After a functional PFO closure peak exercise combined with a Valsalva strain facilitates the reoccurrence of RLS in stroke patients.
- Research Article
2
- 10.1186/1471-2261-11-54
- Aug 26, 2011
- BMC Cardiovascular Disorders
BackgroundAs previously reported there is evidence for a reduction in right to left shunt (RLS) in stroke patients with patent foramen ovale (PFO). This occurs predominantly in patients with cryptogenic stroke (CS). We therefore analysed factors associated with a shunt reduction on follow-up in stroke patients suffering of CS.MethodsOn index event PFO and RLS were proven by transesophageal echocardiography and contrast-enhanced transcranial Doppler-sonography (ce-TCD). Silent PE was proved by ventilation perfusion scintigraphy (V/Q) within the stroke work-up on index event; all scans were re-evaluated in a blinded manner by two experts. The RLS was re-assessed on follow-up by ce-TCD. A reduction in shunt volume was defined as a difference of ≥20 microembolic signals (MES) or the lack of evidence of RLS on follow-up. For subsequent analyses patients with CS were considered; parameters such as deep vein thrombosis (DVT) and silent pulmonary embolism (PE) were analysed.ResultsIn 39 PFO patients suffering of a CS the RLS was re-assessed on follow-up. In all patients (n = 39) with CS a V/Q was performed; the median age was 40 years, 24 (61.5%) patients were female. In 27 patients a reduction in RLS was evident. Silent PE was evident in 18/39 patients (46.2%). Factors such as atrial septum aneurysm, DVT or even silent PE were not associated with RLS dynamics. A greater time delay from index event to follow-up assessment was associated with a decrease in shunt volume (median 12 vs. 6 months, p = 0.013).ConclusionsIn patients with CS a reduction in RLS is not associated with the presence of a venous embolic event such as DVT or silent PE. A greater time delay between the initial and the follow-up investigation increases the likelihood for the detection of a reduction in RLS.
- Research Article
35
- 10.1159/000430998
- Jul 1, 2015
- Cerebrovascular Diseases
Background: For patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), it is unknown whether the magnitude of right-to-left shunt (RLSh) measured by contrast transcranial Doppler (c-TCD) is correlated with the likelihood an identified PFO is related to CS as determined by the Risk of Paradoxical Embolism (RoPE) score. Additionally, for patients with CS, it is unknown whether PFO assessment by c-TCD is more sensitive for identifying RLSh compared with transesophageal echocardiography (TEE). Our aim was to determine the significance of RLSh grade by c-TCD in patients with PFO and CS. Methods: We evaluated patients with CS who had RLSh quantified by c-TCD in the Multicenter Study into RLSh in Cryptogenic Stroke (CODICIA) to determine whether there is an association between c-TCD shunt grade and the RoPE Score. For patients who underwent c-TCD and TEE, we determined whether there is agreement in identifying and grading RLSh between these two modalities. Results: The RoPE score predicted the presence versus the absence of RLSh documented by c-TCD (c-statistic = 0.66). For patients with documented RLSh by c-TCD, shunt severity was correlated with increasing RoPE score (rank correlation (r) = 0.15, p = 0.01). Among 293 patients who had both c-TCD and TEE performed, c-TCD was more sensitive (98.7%) for detecting RLSh. Of the 97 patients with no PFO identified on TEE, 28 (29%) had a large amount of RLSh seen on c-TCD. Conclusions: For patients with CS, severity of RLSh by c-TCD is positively correlated with the RoPE score, indicating that this technique for shunt grading identifies patients more likely to have pathogenic rather than incidental PFOs. c-TCD is also more sensitive in detecting RLSh than TEE. These findings suggest an important role for c-TCD in the evaluation of PFO in the setting of CS.
- Research Article
- 10.1161/str.47.suppl_1.wp214
- Feb 1, 2016
- Stroke
Introduction: Patent Foramen Ovale (PFO) is the most common right-to-left shunt (RLS) and is often found in young patients with stroke related to paradoxical embolism. Contrast-Enhanced Transesophageal Echocardiography (TEE) is considered a gold standard to visualize PFO. Transcranial Doppler (TCD) with bubble test is often used to detect RLS with good correlation to TEE for the diagnostic of PFO. More recently, Transcranial Color Coded Sonography (TCCS) which included B-mode and color coded imaging has overcome TCD in many clinical applications but the accuracy of TCCS for detection of RLS and PFO has not been systematically evaluated. Hypothesis: To determine if the TCCS is an accurate tool to identify both PFO and RLS. Methods: We investigate 106 patients with ischemic stroke under 55 years-old admitted from 2012 to 2014 in a tertiary academic hospital. Patients were evaluated with TEE, TCD and TCCS, and all exams included a saline bubble test. The examiners were blinded for the other tests results. Kappa agreement was calculated inter-examiners for TCCS and TCD. Accuracy of TCCS was calculated in comparison to TEE. Results: We detected a RLS in 54 (50.9%) patients (age mean 43.9 ± 8.2) with kappa agreement 0.92 (95%CI 0.78-1.0) when performed TCCS and TCD. TEE and TCSS were positive in 23/98 (23.4%) and TEE did not reveal contrast in 20/98 (20.4%). In 30 (28.3%) patients only TEE revealed a PFO. TCSS had a sensitivity of 88.4% (95%CI 0.68-0.97), specificity of 72.2% (95%CI 0.60-0.81) and positive likelihood ratio of 3.18 (2.14-4.73) of the diagnosis of PFO. Conclusion: TCCS and TCD had an excellent agreement. TCCS has a good accuracy for the detection of PFO and RLS in young patients with stroke.
- Research Article
1
- 10.1186/s41983-021-00273-9
- Feb 15, 2021
- The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
BackgroundContrast-enhanced transcranial duplex (c-TCD) might be more sensitive than transesophageal echo (TEE) for detection of right to left shunting (RLS), which misses some cases with substantial RLS and might be valuable for prediction of recurrent stroke or transient ischemic attack in patients with PFO. Our aim is to detect sensitivity and specificity of contrast-enhanced TCD in detection of RLS among stroke patients with patent foramen ovale (PFO) in comparison to TEE.MethodsTEE and contrast-enhanced TCD for cryptogenic stroke patients with PFO were done to detect right to left shunting.ResultsOn testing characteristics of TCD in detecting RLS compared to the gold standard of TEE, TCD sensitivity was 85.7%, specificity was 100%, negative predictive value was 96.55%, and positive predictive value was 100%.ConclusionWe concluded that PFO is considered an important hidden etiology for ischemic stroke. Contrast-enhanced TCD is considered sensitive method for detection of right to left shunting among PFO patients.
- Research Article
- 10.3877/cma.j.issn.1672-6448.2016.03.006
- Mar 1, 2016
Objective To compare the safety, stability and effectiveness of modified right heart contrast echocardiography and traditional right heart contrast echocardiography in detection of intra- or extra-cardiac right to left shunt (RLS). Methods (1) Microscopic analysis: After agitating 10 times or 20 times (AS10, AS20, ASb10, ASb20), two right heart contrast agent (modified: 8 ml saline+ 1 ml blood+ 1 ml air; traditional: 9 ml saline+ 1 ml air) underwent the microscopic examination to compare the bubble size, bubble number and red blood cell morphology; (2) Clinical experiment: Thirty-two inpatients or outpatients suspected of RLS (cryptogenic stroke, transient ischemic attack, migraine with aura or platypnea-orthodeoxia syndrome) in Sichuan Provincial Hospital were selected. All patients underwent two right heart contrast echocardiography in which contrast agents had been agitated for 10 and 20 times (AS10, AS20, ASb10, ASb20). Monitor the right heart developing time, RLS and the oxygen saturation change were monitored and the RLS were semi-quantitatively analyzed. The indirect bilirubin and urobilinogen change after the contrast echocardiography were compared. Results Microscopic analysis showed that red blood cell membrane damaged more seriously as the agitated times increased. ASb20 generated more bubbles and the number of bubbles was about 4 times of that of AS10 generated (t=14.180, P<0.01); but the bubble size difference was not significant. With the modified method, RLS were detected in 22 patients (68.8%, 22/32). With the traditional method, RLS were detected in 18 patients (56.3%, 18/32). The results of semi-quantitative analysis of RLS was significant different between any two groups (ASb20 vs. AS10, AS20, ASb10: χ2=13.567, 11.646 and 9.001, respectively; ASb10 vs. AS10, AS20: χ2=9.125 and 2.589; AS20 vs. AS10: χ2= 8.127; all P<0.01). The change of oxygen saturation, the indirect bilirubin and urobilinogen were not significant after the contrast echocardiography. Conclusions Modified right heart contrast echocardiography is a safe, stable and cost-effective method to detect RLS. The semi-quantitative analysis of RLS with modified right heart contrast echocardiography and their relationship with clinical accident needs further research. Key words: Right heart contrast echocardiography; Microbubble; Right-to-left shunt; Patent foramen ovale
- Research Article
16
- 10.1080/00207454.2019.1672681
- Oct 7, 2019
- International Journal of Neuroscience
Objectives: In this study, we aimed to explore the influence of right-to-left shunt (RLS) presence on the clinical features of migraine and to follow-up on the post-operative curative effect of transcatheter patent foramen ovale (PFO) closure on migraine features.Methods: A total of 103 migraine patients were divided into a mild volume RLS group, moderate volume RLS group, large volume RLS group and non-RLS group in accordance with contrast enhancement transcranial Doppler (c-TCD) findings. The Visual Analogue Scale (VAS) score, migraine frequency, migraine duration, migraine disability assessment (MIDAS) and headache impact test-6 (HIT-6) scores were compared amongst the different groups. A total of 39 patients with moderate or large RLS received transcatheter PFO closure and those patients were followed up by the same criteria.Results: The attack frequency, HIT-6 and MIDAS scores amongst the migraine patients with moderate or large RLS were significantly higher than those in patients from the mild RLS group and non-RLS group (p < .05). The transcatheter closure was successful in all patients (n = 39), and no post-operative complications were observed during the hospitalisation and follow-up period. The differences in VAS, HIT-6 and MIDAS scores as well as the headache duration were statistically significant amongst patients before and after PFO closure (p < .05).Conclusions: Moderate to large RLS significantly influenced the clinical features of migraine, and transcatheter PFO closure could significantly relieve headache symptoms in migraine patients with PFO.
- Research Article
3
- 10.2174/0115734056284889240102095034
- Feb 26, 2024
- Current medical imaging
This study aims to comprehensively assess the characteristics of patent foramen ovale (PFO) in relation to Cryptogenic Strok (CS) by utilizing transesophageal echocardiography (TEE) and contrast transthoracic echocardiography (c-TTE) and to identify high-risk factors associated with PFO-related CS. Transcatheter PFO closure has demonstrated its effectiveness in preventing PFO-related CS. Therefore, understanding the specific structural attributes of PFO associated with CS is imperative. Enrollment comprised 113 test patients who experienced CS in conjunction with PFO and 117 control patients diagnosed with migraine with PFO but without a history of stroke. The characteristics of the PFO were observed by TEE and c-TTE. A comparative analysis was undertaken to assess the variations in PFO characteristics between the test patients and controls, and to uncover the independent factors relevant to CS. The patients in the test group were older than the controls. Both the height and length of the PFO during Valsalva exhibited greater dimensions in the test group when contrasted with controls. Notably, the test group presented higher incidence rates of low-angle PFO (defined as an angle between the inferior vena cava (IVC) and PFO ≤ 10°) and atrial septal aneurysm (ASA) as contrasted with the control group. Right-to-left shunt (RLS) III during Valsalva demonstrated a significantly elevated occurrence within the test group as opposed to the controls. Conversely, RLS II during Valsalva exhibited a significantly higher frequency in the controls in contrast to the tests. No significant disparities were observed between the two groups with respect to RLS I during Valsalva and all grades of RLS at rest. Multivariate analysis revealed that the length of the PFO during Valsalva, the presence of ASA, RLS III during Valsalva and low-angle PFO were independent relevant factors associated with CS. The length of the PFO tunnel, low-angle PFO, RLS III during Valsalva and the presence of ASA were independent risk factors for CS. The combined utilization of TEE and c-TTE may prove valuable in identifying PFO patients at a heightened risk of CS and in facilitating the screening process for transcatheter PFO closure.
- Discussion
1
- 10.1111/echo.13021
- Sep 1, 2015
- Echocardiography
© 2015, Wiley Periodicals, Inc. DOI: 10.1111/echo.13021 Echocardiography LETTER TO THE EDITOR Patent Foramen Ovale and Atrial Septal Defect: Utility of Alternative Imaging Modalities for the Diagnosis of Patent Foramen Ovale and Atrial Septal Defect Dear Editor, We read with interest the article “Patent Foramen Ovale (PFO) and Atrial Septal Defect (ASD)” by Hari et al. 1 The article is a review describing the anatomy and embryology of the atrial septum and the diagnosis of PFO and ASD using echocar- diography. The authors mention the importance of transesophageal echocardiography (TEE) in visualizing the atrial septal anatomy, measuring the degree of right-to-left shunting (RLS), and determining the type and size of the closure device preprocedure. For the readers of Echocar- diography, we would like to provide additional information on the accuracy, optimal protocol, advantages, and limitations of the different imag- ing modalities that are commonly used for the diagnosis of intracardiac RLS. Transthoracic echocardiography (TTE) is the most commonly used method for diagnosing cardiac RLS due to its low cost and easy avail- ability. Conventional TTE has a low sensitivity of 49% but a high specificity of 99% when com- pared with TEE. 2 A recent review comparing dif- ferent protocols used in conventional TTE found that utilizing different contrast agents, different microbubble cutoffs for a positive study, and different cardiac cycle cutoffs did not alter the accuracy of conventional TTE. 2 Harmonic imag- ing capability improves the sensitivity of TTE while compromising specificity. 3,4 The accuracy of TTE harmonic imaging may be enhanced by the addition of blood to the agitated saline contrast, injection of contrast immediately before the provocation maneuver (as opposed to during), and when the test is considered pos- itive for RLS by the appearance of ≥1 microbub- ble in the left atrium within 3 cardiac cycles. 4 TTE, with or without harmonic imaging, is lim- ited by its inability to accurately assess the atrial septal anatomy. The Valsalva maneuver causes inflation of the lungs and shifting of the dia- phragm which results in a transient loss of image as bubbles cross the interatrial septum; this may partly explain the lower accuracy of TTE. 5 Transcranial Doppler (TCD) bubble study may be preferable for detecting RLS due to its low cost, high accuracy, and noninvasive nat- ure. TCD indirectly assesses for a RLS by injec- tion of agitated saline contrast and detection of bubbles after a provocation maneuver through insonation of the middle cerebral arteries. When compared to TEE, TCD has a sensitivity of 97% but a lower specificity of 93% likely due to its inability to differentiate between cardiac and pulmonary RLS. A recent review observed that using different contrast agents, changing the timing and type of provocation maneuvers and insonating unilateral versus bilateral middle cerebral arteries did not affect the accuracy of TCD for detecting RLS. 6 However, increasing the microembolic threshold for a positive TCD to 30 microbubbles significantly improves the specificity of TCD without compromising sensi- tivity compared to the diagnosis of PFO by heart catheterization. 7 As Hari et al mentioned, TEE is essential for visualizing the atrial septal anatomy, measuring RLS severity and determining the type and size of a potential closure device. However, 10% of PFOs may still be missed with TEE. A recent meta-anal- ysis comparing the diagnostic accuracy of TEE to confirmation by autopsy, cardiac surgery, and/or cardiac catheterization demonstrated TEE to have a sensitivity of 89% and specificity of 91%. 8 TEE has the limitation of being time-consuming, uncomfortable for the patient, and has a low risk of esophageal bleeding or perforation. We recommend utilizing TCD as an initial screening test with TEE used as a subsequent confirmatory test. In stroke patients, TEE is still essential for the diagnosis of other etiologies of stroke including an intracardiac thrombus and to assess the left atrial appendage or the presence of aortic disease. Disclosures: Dr. Tobis is a consultant for St. Jude Medical, Inc. and W.L. Gore, Inc. No funding was provided to write this letter. Dr. Mojadidi has no disclosures.
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