Management of Platypnea-Orthodeoxia Syndrome by Transcatheter Closure of Atrial Communication: Hemodynamic Characteristics, Clin

Platypnea-orthodeoxia syndrome (POS) is defined as dyspnea and arterial desaturation induced by upright posture and relieved by recumbence.1,2 Although the precise underlying mechanism by which an atrial communication accounts for this disorder is unknown, it is thought to be secondary to right to left shunt through an atrial septal defect, most commonly a PFO.3 It has been reported in association with increased4 or normal right-sided heart pressures.5,6 POS is a rare disorder with no more than 50 cases described since initially reported in 1949.7 Management of POS by surgical8 and percutaneous closure of the atrial defect has been previously reported.9–11 The present study prospectively assessed the baseline characteristics and the clinical and echocardiographic outcome of 18 consecutive patients with POS who underwent percutaneous atrial communication closure at Massachusetts General Hospital. This is the largest reported collection of patients with POS. Methods Patient population. The patient population is comprised of 18 patients with platypnea and orthodeoxia who underwent percutaneous transcatheter device closure of a PFO or ASD at the Massachusetts General Hospital between January 1995 and June of 2002. The diagnosis of POS was established when patients with upright posture dyspnea and arterial desaturation were shown to have an interatrial communication with right-to-left shunt by 2-D or transesophageal echocardiography (TEE) with color flow Doppler and microbubble administration (Figure 1). Closure of the atrial communication was performed using the Buttoned (n = 6), CardioSEAL (n = 11), or Amplatzer (n = 1) occluder devices as previously described.9–11 Atrial communication closure was performed under general anesthesia with TEE and fluoroscopic guidance. Patients received Cefazoline 1 gram IV at the time of the procedure, followed by 1 gram IV every 8 hours for an additional 2 doses. Vancomycin 1 gram IV at the time of procedure, followed by an additional dose 12 hours later, was used in patients allergic to penicillin. Patients were anticoagulated at the time of the procedure with unfractionated IV heparin (70–100 U/kg). Prior to device implantation, patients underwent percutaneous diagnostic cardiac catheterization from the right femoral artery and right femoral vein. Hemodynamic and oxygen saturation measurements were performed. A 7 French (Fr) Goodale Lubin catheter was used to cross from the right atrium into the left atrium across the atrial communication. The catheter was then advanced into the right upper pulmonary vein and exchanged for a 5.5 Fr pigtail catheter with 1 cm radiopaque markers over a 0.035 = 2 was chosen, advanced through the Mullins sheath and deployed under cinefluoroscopy and TEE guidance. Optimal placement of the device was confirmed by TEE and by the presence of minimal or no shunt after deployment by color flow Doppler and microbubble administration. Two-dimensional echocardiography, chest x-ray and electrocardiogram were repeated 24 hours post-procedure prior to hospital discharge. Patients were discharged on aspirin 325 mg daily and subacute bacterial endocarditis prophylaxis for a 6-month period. In patients with aspirin allergy, clopidogrel 75 mg daily or ticlopidine 250 mg twice daily were prescribed. Follow-up Evaluation. Patients were followed clinically and echocardiographically at 24 hours, 1 month, 3 months, 6 month, and 12 months after device implantation and yearly thereafter. Follow-up information was obtained by periodical visits with physicians. When necessary, local physicians were contacted for further information and medical records were reviewed. Echocardiographic examinations were reviewed and assessed for the presence of residual shunt. Residual shunt was determined by 2-D echocardiography, color flow Doppler and agitated saline solution contrast injection from an antecubital vein and were categorized as follows: (0) None: no microbubbles in the left atrium following administration of agitated saline, (1) Small: the presence of 3–9 microbubbles in the left atrium following administration of agitated saline, (2) Moderate: 10–30 microbubbles in the left atrium following administration of agitated saline, (3) Large: more than 30 microbubbles in the left atrium following administration of agitated saline.12 Excursion of the atrial septum into the left or right atrium was classified as hypermobile if it extended at least 11 mm beyond the plane of the atrial septum and as aneurysm if it exceeded 14 mm.12,13 Follow-up events included death, recurrent dyspnea or arterial desaturation on upright posture, and need of reintervention for significant residual shunt or device malalignment. Statistical Analysis. All data were entered into a computerized database specifically designed for this study. Data are presented as mean ± SD and p values Patient Population. The patient population included 18 consecutive patients with POS who underwent transcatheter closure of their atrial communication. Baseline characteristics of the patient population are shown in Table 1. There were 10 (56%) males and 8 (44%) females with a mean age of 65 ± 18 (range 19–83) years. All patients had platypnea and orthodeoxia with a mean supine oxygen saturation of 92.5 ± 6.0 % and upright posture oxygen saturation of 82.6 ± 5.4%. Associated conditions included: ischemic cerebrovascular accident and pulmonary embolism (in the same patient), pulmonary hypertension, severe tricuspid regurgitation, obstructive sleep apnea and chronic obstructive pulmonary disease. Procedural Results. The interatrial communication was a PFO in 16 (89%) patients and a secundum ASD in 2 (11%). PFO or ASD stretched diameter by both cinefluoroscopy and TEE was 12.5 ± 4.5 (5–23) mm. Seven (39%) patients had a concomitant atrial septal aneurysm and 4 (22%) of patients had atrial septal hypermobility. The mean right atrial pressure was 9.6 ± 5.6 (17–3) mmHg, mean left atrial pressure was 12.5 ± 13.2 (3–60) mm Hg. and mean right ventricular pressure was 13.9 ± 7.8 (6.3–34.4) mmHg. Right to left shunt was present in all patients. The mean left ventricular ejection fraction was 62.3 ± 9 (44–78)%. ASD or PFO closure was performed using a buttoned device (Sideris) in 6 patients, CardioSEAL device in 11 patients, and Amplatzer PFO Occluder in 1 patient. The average device size was 29.5 ± 7.7 (14–48) mm resulting in a device size/ atrial communication stretched diameter size ratio of 2.5 ± 0.7. Successful device size implantation was accomplished in 18 (100%) patients. Effective occlusion (none or small residual shunt) was achieved in 18 (100%) patients immediately after device deployment. Full occlusion (no shunt) was present in 10 (55%) patients. In 1 patient with PFO persistent right-to-left shunt was observed after placement of a 30 mm CardioSEAL device with a 3.0 device-to-ASD ratio. During the same procedure a second counter occluder was placed achieving effective closure. No other septal defects were seen. At 24 hours post device placement full occlusion was present in 12 (66%), small shunt in 4 (22%), moderate shunt in 2 patients (11%), and large shunt in no patient (Table 2). Upright mean oxygen saturation increased from 82.6 ± 5.4 to 96.1 ± 2.2 % (p In-hospital complications. There were no deaths or major adverse events associated with device implantation. Follow-Up. The mean follow-up was 2.9 ± 2.2 years. There were no deaths. Recurrent platypnea or orthodeoxia. Platypnea and orthodeoxia, associated with moderate shunt and device malalignement occurred in an 80-year-old female 6 years after successful device implantation. Upon reintervention portions of the device appeared to be non-adherent to the atrial septum, no other abnormalities including device integrity were noted. This kind of non-adherence was not seen in any other patient. She underwent closure with a new device and had no symptom recurrence, no residual shunt, and correct device position in subsequent clinical and echocardiographic assessments. Kaplan-Meier analysis revealed an actuarial risk of recurrent platypnea-orthodeoxia of 4.6% at 2.9 years of follow-up. Reintervention. Two patients required reintervention for significant residual shunt or symptom recurrence, resulting in a 9.2% actuarial freedom from reintervention at 2.9 years of follow-up. Both patients underwent repeat percutaneous device closure. The first one, was the patient described above with device malalignement, moderate shunt, and symptom recurrence 6 years after the initial procedure. The second one, a 67-year-old male with persistence of moderate shunt but no symptoms 1 month after initial procedure requiring successful repeat transcatheter closure. These patients’ initial devices were a Sideris buttoned and a CardioSEAL device, respectively. No arm fractures or lost of integrity were identified in any patient. Therefore, the actuarial freedom from combined endpoint (reintervention and recurrence of symptoms) was 79% at 2.9 ± 2.2 years (Figure 3). Residual Shunt at Follow-up. Follow-up echocardiography showed total occlusion in 13 (72%) patients, small shunt in 2 (11%) patients, and moderate shunt in one patient. No patient had large shunts. Finally, a moderate shunt associated with symptoms was present in two patients at 1 month and 6 months of follow-up, requiring repeat transcatheter closure as described above. Discussion We report the largest single institution collection of patients with POS to undergo transcatheter closure of PFO or ASD. The present study demonstrates that this technique is safe and effective; has a high success rate, a low incidence of procedural and in-hospital complications, and excellent immediate and follow-up results. Even though the precise mechanism for platypnea and orthodeoxia is not yet known the most common cause is a right-to-left shunt through an interatrial communication. The cause of right-to-left shunt across this communication is not completely understood. There are several potential explanations: decreased right atrial compliance,14 inferior vena cava15 or persistent eustachian valve16 redirection of flow toward an interatrial communication, upright posture stretching of septal defect and transient (rather than sustained) interatrial pressure differentials during the cardiac cycle.6,7 Other causes of POS include: intrapulmonary shunts,17 pulmonary parenchymal disease,18 aortic aneurysm,19 aortic elongation,20 autonomic dysfunction,21 pericardial effusion,22 and postpneumonectomy.23 Treatment options have included correction of hypovolemia,24 opiates25 and closure of the interatrial communication. Mixed and anecdotal results of surgical closure have been reported. Seward et al.2 reported their results in 5 patients with POS who underwent surgical closure. They had no operative mortality, but one patient died 1 week later from massive cerebral infarction. There is no comment on non-fatal surgical complications. Transcatheter occlusion offers the advantages of closure of the defect without the disadvantages of open-heart surgery.9–11 In the present study, the atrial septal closure device was successfully deployed, and an effective occlusion (none or trivial shunt) was achieved in all patients. Procedural and in-hospital complications were low. There were no deaths and no adverse events associated with the procedure. We demonstrated excellent immediate results with an increase in mean oxygen saturation from 82.6% to 96.1% and resolution of symptoms in all patients. Recurrence of platypnea and orthodeoxia occurred in only one patient six years after successful device implantation. In addition, the present study also showed that the need for surgical or transcatheter intervention for device malalignement or significant shunt was low. These findings are reflected in the 79% freedom from symptom recurrence and reintervention at follow-up. Although, the device was successfully deployed in all patients at the time of procedure, 2 patients required repeat catheter intervention for significant shunt associated with device malalignement. POS has been associated with increased4 and normal.5,6 right-sided heart pressures. In this study, we found that 6 (33%) patients had high right atrial pressure (9.6 ± 5.6 mmHg) and 4 (22%) had high right ventricular pressure (26.5 ± 3.1 mmHg). Three (17%) patients had high left atrial pressure (33 ± 23.4 mmHg), which was related to concomitantly elevated right atrial pressure in 2 patients. No patient had elevated right ventricular pressure in the absence of elevated right atrial pressure. Despite normal right-sided heart pressures in the majority of patients (66%), right-to-left shunt was present in all. This observation is in agreement with previous studies showing that the presence of high right-sided pressures is not a requisite for right-to-left shunt.5,6 Although two of our patients had a condition associated with POS and right-to-left shunt (pulmonary hypertension and severe tricuspid regurgitation), other previously described associations, i.e. prominent eustachian valve, aortic abnormalities, right atrial flow redirection, etc.., were not present or could not be demonstrated. Comparison With Previous Studies of Percutaneous Transcatheter Closure of PFO or ASD for treatment of POS. Rao et al.,10 reported the results of a multicenter study using a transcatheter buttoned device for closure of PFO and ASD in 10 patients with POS and a mean oxygen saturation of 76%. Successful device implantation was achieved in all patients, and complete closure was accomplished in 50% of patients (the rest had “trivial” residual shunt). No complications were encountered. Mean oxygen saturation increased to 95% and persistent resolution of symptoms was seen in all patients at a median follow-up of 12 months. In 2 patients, pulmonary artery pressure was elevated. Waight et al.11 reported the results of transcatheter closure in 4 patients with POS using the PFO and ASD Amplatzerer devices. Successful closure in all patients with no complications and an increase in oxygen saturation from 81% to 96% with complete resolution of symptoms were described. Two patients had a mildly elevated right atrial pressure. No follow-up data is available. Landzberg et al.26 reported their experience of percutaneous PFO closure in 8 patients with POS using the clamshell (double umbrella) device. Device embolization occurred in 2 patients requiring transcatheter extraction and deployment of a second device. Nonsustained atrial and ventricular arrhythmia occurred in one patient. Minimal angiographic evidence of residual right-to-left shunt was seen immediately postimplantation in four patients. All patients experienced an immediate rise in oxygen saturation to > 95% and sustained resolution of symptoms at latest follow-up (29–63 months). None of these patients had an elevated right atrial pressure. Finally, Godart, et al.,27 reported the results of transcatheter closure in 11 patients with symptomatic hypoxemia and evidence of right-to-left shunt across a PFO or ASD on transesophageal echocardiography. Only 6 of them had associated platypnea and orthodeoxia. All but one were successfully occluded. In 1 patient, delivery of the device failed due to kinking of the introducer sheath. Two supraventricular arrhythmias and a cerebrovascular accident occurred following the procedure. No desaturation of recurrence of symptoms occurred during follow-up (up to 30 months). All patients had normal right-sided pressures. Our results compare favorably with those obtained with surgical or percutaneous closure of PFO or ASD for patients with POS. We achieved successful device implantation, effective occlusion, oxygen saturation improvement, and complete symptom resolution in all patients. We had no in-hospital mortality, minimal in-hospital morbidity and 4.6% recurrence of symptoms at a mean follow-up of 2.9 years. The learning curve, technical improvement, and patient selection may account for these differences. Limitations of the Study. We acknowledge some limitations of the present study. First, our patient population was a selected cohort referred to our center for percutaneous PFO or ASD closure and might differ from other series published. Second, the low incidence of POS and the small number of symptom recurrence underpowered the present study to identify predictors of recurrent events or re-intervention after device implantation. Because the incidence of recurrent symptoms was low, longer-term results are necessary before drawing final conclusions. Third, the pathophysiology and hemodynamic mechanisms involved in POS are not completely understood. Further study in these areas is necessary before a complete etiologic and therapeutic theory can be brought about.

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