Nonsurgical Closure of a Patent Foramen Ovale in aPatient With Carcinoid Heart Disease and Severe

Hypoxia From Interatrial Shunting

John Marenco,1 MD, Shapur Naimi,1 MD, Ziyad Hijazi,2 MD, Ayan Patel,3 MD,and Natesa Pandian,3* MD

We report the percutaneous transcatheter closure of a patent foramen ovale using anAmplatzer septal occluder in a rare patient with carcinoid heart disease involving both theright and left heart who presented with severe hypoxemia secondary to intra-atrialshunting. We believe this is the first report of this technique being utilized in a patient withcarcinoid heart disease and it may represent an alternative to surgical closure in thesepatients at high risk for surgical complications. Cathet. Cardiovasc. Intervent. 51:210–213, 2000. © 2000 Wiley-Liss, Inc.

Key words: carcinoid heart disease; malignant carcinoid syndrome; valvular heart dis-ease; heart septal defect, atrial

INTRODUCTION

A 58-year-old woman presented with a 4-month his-tory of fatigue, dyspnea on exertion, flushing, and diar-rhea. The initial work-up included two-dimensionalechocardiography that revealed normal left ventricularfunction and no significant valvular disease. Pulmonaryfunction tests were normal. Computerized tomography ofthe abdomen demonstrated a 13-cm multiloculated massin the left lobe of the liver and a lesion in the terminalileum at the ileocecal valve. Colonoscopy identified themass in the terminal ileum and biopsy was consistentwith carcinoid disease. A 24-hr urine 5 hydroxy-in-doleacetic acid (HIAA) level was markedly elevated at190 mg/24 hr (normal5 2–8 mg/24 hr) consistent withthe diagnosis of carcinoid disease. Medical therapy withOctreotide was initiated with only a transient improve-ment in symptoms and surgical debulking of the tumorby right hemicolectomy and wedge resection of the liverwas recommended. Preoperative arterial blood gas onroom air revealed pH5 7.36, partial pressure of oxygen(PaO2) 5 65 mm Hg, and partial pressure of carbondioxide (PaCO2) 5 25 mm Hg. Baseline room air arterialsaturation (SaO2) was 90%. After induction of anesthesiaand intubation using positive pressure ventilation, thepatient became profoundly hypoxemic with a reductionin the SaO2 to 61% and PaO2 to 45 mm Hg despite afraction of inspired oxygen (FiO2) 5 100%. An intraop-erative transesophageal echocardiogram was performed(Fig. 1). Doppler echocardiography showed severe pul-monic and tricuspid valve regurgitation, moderately se-vere aortic regurgitation, and mild tricuspid valve steno-

sis. The tricuspid valve leaflets were thickened andrestricted. The right ventricle was markedly enlargedwith mildly diminished function. Left ventricular sizeand function was normal. Color doppler of the interatrialseptum clearly demonstrated right-to-left shuntingthrough a patent foramen ovale (Fig. 2) and contrastbubble study was markedly positive. A pulmonary arterycatheter revealed central venous pressure (CVP) of 24mm Hg, pulmonary artery pressure (PAP) of 30/15 mmHg, and pulmonary artery capillary wedge pressure(PACWP) of 12 mm Hg. Surgery was deferred and thepatient was admitted to the intensive care unit. Withionotropic support and withdrawal of anesthesia, she wassuccessfully extubated but remained severely hypoxic.Given the inability to tolerate general anesthesia andintubation, surgical closure of the PFO was not feasibleand it was decided to attempt closure of the patentforamen ovale using an Amplatzer septal occluder (AGAMedical, Golden Valley, MN), a percutaneous, transcath-

1Division of Cardiology, New England Medical Center Hospitals,Boston, Massachusetts2Section of Pediatric Cardiology, University of Chicago Hospi-tals, Chicago, Illinois3Cardiovascular Imaging and Hemodynamic Laboratory, Divi-sion of Cardiology, New England Medical Center, Boston,Massachusetts

*Correspondence to: Dr. Natesa Pandian, Department of Cardiology,New England Medical Center, 750 Washington Street, Boston, MA02111. E-mail: jmarenco@lifespan.org

Received 23 February 2000; Revision accepted 16 May 2000

Catheterization and Cardiovascular Interventions 51:210–213 (2000)

© 2000 Wiley-Liss, Inc.

eter, atrial septal defect closure device. At cardiac cath-eterization, pressure measurements and oxygen satura-tions were measured prior to balloon inflation, with trialballoon inflation and after closure (Table I). The defect

was closed with a 35-mm Amplatzer PFO occluder.Flouroscopy showed the device in good position andaortic oxygen saturations improved from 86% to 95%,indicating a reduction in right-to-left shunting. A trans-thoracic echocardiogram was performed and color Dopp-ler of the interatrial septum showed the absence of inter-atrial flow. The patient was slowly weaned fromsupplemental oxygen without difficulty and remainedhemodynamically stable. After a brief stay at a rehabil-itation facility, she underwent successful right hemico-lectomy and wedge resection of the liver with a markedimprovement in her symptoms.

DISCUSSION

Carcinoid heart disease occurs in nearly two-thirds ofpatients with the carcinoid syndrome [1]. The etiology

Fig. 1. Transesophageal echocardiographic images (four-chamber views, systolic frames).Left: Systolic frame demonstrating thickened tricuspid valve leaflets with incomplete closure,severe tricuspid regurgitation, and bowing of the atrial septum toward the left atrium suggestiveof elevated right atrial pressure. Right: Color flow doppler demonstrating severe eccentrictricuspid regurgitation.

Fig. 2. Transesophageal echocardiographic image of the rightand left atrium with color doppler flow demonstrating right-to-left shunting across a patent formamen ovale.

TABLE I. Saturation and Pressure Measurements at CardiacCatheterization*

Preclosure Trial closure Postclosure

O2 SaturationSVC 56% 59% 61%Aortic 86% 97% 95%

Pressure (mm Hg)RA mean 13 15 17PA 40/12Systemic arterial 166/57 182/67 184/67

*SVC 5 superior vena cavae; RA5 right atrium; PA5 pulmonary artery.

Carcinoid Heart Disease 211

has been linked to humoral factors secreted by these raretumors of neuroendocrine cell origin. Serotonin is thebest characterized of these humoral factors and eleva-tions have been correlated with valvular abnormalities[2]. Carcinoid heart disease occurs most commonly inpatients with liver metastasis where the humoral factorssecreted by the tumor are released into the right side ofthe heart [3]. The characteristic lesion is a fibrous plaquethat commonly involves the endocardial tissue and thetricuspid and pulmonic valves. Regurgitation of the tri-cuspid and pulmonic valve is found in the majority ofpatients and leaflet thickening and retraction often lead topulmonic and tricuspid stenosis. Due to the metabolismof humoral factors in the lungs, involvement of the mitraland aortic valves is less common and usually seen in thepresence of a patent foramen ovale or pulmonary carci-noid disease [4]. Carcinoid tumors are generally slow-growing tumors and recent advances in medical andsurgical treatment have improved the survival and re-duced symptoms in many of these patients [5]. Unfortu-nately, patients with carcinoid heart disease continue tohave progressive symptoms of right-sided heart failureand cardiac involvement has become the major cause ofmortality. Historically, treatment has been primarily sur-gical. Perioperative mortality rates for valve replacementin these patients remains disturbingly high, however.Connolly et al. [6] looked at 26 patients with symptom-atic carcinoid heart disease and reported a 35% periop-erative mortality. Robolio et al. [7] reported a 63% peri-operative mortality in 19 patients. Bleeding and rightheart failure were the most common causes of death.

Cyanosis and hypoxemia associated with carcinoidsyndrome has been reported previously. Stewart et al. [8]reported such a patient in whom right-to-left shuntingwas attributed to intrapulmonary shunting. Blick et al. [9]reported a patient with right-sided carcinoid heart diseasein whom right-to-left shunting through a patent foramenovale was documented and successfully corrected bysurgery. Bogliolo et al. [10] and Millward et al. [11] eachreported a patient with both left and right heart involve-ment of carcinoid heart disease and a large right-to-leftshunt through a patent foramen ovale.

We report an additional case of carcinoid heart diseaseinvolving both the right and left heart presenting ashypoxemia from right-to-left shunting through a patentforamen ovale. The current case is particularly interest-ing for several additional reasons. First, this case high-lights how rapidly carcinoid valvular disease can occur.Echocardiographic evidence of severe valvular disease inthis patient developed over just 6 months. Although theetiology of endocardial plaques and valvular disease incarcinoid syndrome has been investigated, the naturalhistory is poorly characterized in the literature. Second, itdemonstrates the adverse hemodynamic changes that can

accompany intubation and induction of general anesthe-sia on this type of patient. Although intubation withpositive pressure ventilation can have varying hemody-namic effects on the cardiovascular system, in part basedon the type of anesthesia and the volume status of thepatient, right atrial pressure generally increases with littlechange in left atrial pressure [12]. We believe the furtherelevation of right atrial pressure in this patient withsevere tricuspid regurgitation resulted in an increase inthe gradient from the right to left atrium and resulted ina decline in systemic oxygenation. Postmortem studiesshow the presence of a patent foramen ovale in 20% ofadults [13]. This suggests the presence of right-to-leftshunting in patients with carcinoid heart disease may bemore common than previously thought and needs to beconsidered prior to undergoing surgery. Finally, this casedemonstrates the ability to close a patent foramen ovaleand reduce hypoxemia secondary to shunting with apercutaneous transcatheter technique. There is growingexperience with the closure of atrial septal defects andother congenital abnormalities via transcatheter ap-proach. Recent data support the safety and efficacy ofusing this transcatheter technique in the closure of se-cundum type atrial septal defects and the superiority ofthe Amplatzer septal occluder over previous devices[14]. Given the high mortality and complication rates thataccompany cardiothoracic surgery in these patients, thistechnique may be a useful alternative in patients withacute hemodynamic derangements who are at increasedrisk for surgical complications.

Right-to-left shunting through a patent foramen ovalemust be considered in the differential diagnosis of hy-poxemia in patients with carcinoid heart disease andparticular attention paid to those undergoing induction ofanesthesia and intubation. Percutaneous transcatheterclosure of a patent foramen ovale in these patients isfeasible and should be considered in those at increasedrisk for complications of surgical repair.

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