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CARDIOVASCULAR ANESTHESIOLOGY

Massive Cardiac Hypertrophy in a Patient with Danon Disease: An Intraoperative Transesophageal Echocardiographic Evaluation

Alexander J. C. Mittnacht, MD^*, Christine Moung, MD, and Wyman W. Lai, MD, MPH

From the Departments of *Anesthesiology, Pathology, Mount Sinai Medical Center; and Departments of Pediatrics and Radiology, Division of Pediatric Cardiology, Mount Sinai Medical Center, New York City, New York.

Address correspondence and reprint requests to Alexander J. C. Mittnacht, MD, The Mount Sinai Medical Center, Box 1010, One Gustave L. Levy Place, New York, NY 10029. Address e-mail to alexander.mittnacht{at}msnyuhealth.org.

A 14-yr-old male, weighing 60 kg, with hypertrophic cardiomyopathy (HCM) of unknown etiology and severe biventricular dysfunction presented for orthotopic heart transplantation. Intraoperative transesophageal echocardiography (TEE) was used before and after discontinuation of cardiopulmonary bypass (CPB) to guide hemodynamic management. A pulmonary artery catheter was not inserted as per our institutional protocol for pediatric orthotopic heart transplantation. TEE Doppler interrogation of the tricuspid valve regurgitation was used to estimate right-sided systolic pressures, which were half-systemic (systolic maximal instantaneous gradient of 41 mm Hg, central venous pressure 16 mm Hg, with systemic pressure of 112 mm Hg) before CPB. After implantation of the donor heart and discontinuation of CPB, direct measurement of right ventricular pressure by the surgeon revealed less than half-systemic right-sided pressures (40 mm Hg, with systemic blood pressure of 108 mm Hg). The patient was tracheally extubated in the operating room. The postoperative course was uneventful, and the patient was discharged to the referring hospital on postoperative day 6.

Pathologic examination of the excised heart revealed massive intracellular accumulation of glycogen. The diagnosis of Danon disease, a deficiency of lysosome-associated membrane protein-2, was made based on the typical histopathologic findings of glycogen deposition with vacuoles, the massive cardiac hypertrophy, and the ventricular pre-excitation present on electrocardiogram. Diagnostic genetic testing could not be performed because of test coverage denial by the patient's insurance. According to the American Heart Association classification of cardiomyopathies, Danon disease is a genetic primary cardiomyopathy with abnormal glycogen storage, mimicking HCM with or without left ventricular outflow tract (LVOT) obstruction (1–3).

Intraoperative TEE showed hypertrophy of the whole heart without a specific pattern of distribution (Fig. 1 and Video clip 1, please see video loop available at www.anesthesia-analgesia.org). At the midpapillary level, left ventricular free-wall thickness measured 4.1–4.3 cm on transgastric views, and the interventricular septum 5.2 cm (versus 5.9 cm on preoperative magnetic resonance imaging). Because of the degree of hypertrophy, the heart had to be cut in half so as to enable excavation from the chest cavity; it weighed 2.16 kg (Fig. 2). The imaging sector was too small to accommodate the heart in its whole dimensions. The massive hypertrophy resulted in additional technical limitations in TEE image acquisition, including lateral "drop out," decreased far field resolution of the ventricular apex, foreshortening of the ventricular cavities, and large voltage amplitudes resembling electrocardiogram artifacts typical for patients with Danon disease.

View larger version (47K): [in this window] [in a new window]   Figure 1. Midesophageal 4-chamber view showing severe hypertrophy of the heart. The imaging sector, even at the maximum setting, is too small to accommodate the heart in its whole dimensions. IVS = interventricular septum, LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle.

View larger version (117K): [in this window] [in a new window]   Figure 2. Image of the heart after excavation from the chest cavity. The heart had to be cut in half by the surgeon so as to allow removal through the sternotomy incision. LVOT = left ventricular outflow tract, RVOT = right ventricular outflow tract.

The presence or absence of LVOT obstruction is an important determination in the clinical care of patients with cardiac hypertrophy. LVOT obstruction (30 mm Hg) is present in 37% of HCM patients at rest and 70% with exercise (4). LVOT obstruction may also be provoked by altered hemodynamic loading conditions. Various mechanisms have been described to explain the incidence and dynamic pattern of LVOT obstruction. Hypertrophy of the ventricular septum, in the form of a septal bulge, causes narrowing of the LVOT and increases the angle of the flow in the LVOT relative to the mitral valve (MV). The resultant anterior position of the left ventricular papillary muscles relative to the LVOT places the coaptation point of the MV into the path of flow across the LVOT. Systolic anterior motion (SAM) of the MV leaflets is the most common cause of LVOT obstruction (5). The hemodynamic cause of SAM is debated, and the reader is referred to a review of its pathophysiology discussing drag (pushing) versus Venturi (pulling) mechanisms that produce the anterior motion of both MV leaflets (6). Although the anterior leaflet is usually enlarged or elongated, chordal slack is generally necessary for SAM to occur. Restricted MV leaflet motion will prevent "typical" SAM, but significant mitral regurgitation may occur when restriction of motion is limited only to the posterior leaflet (7).

In the case presented here, there was laminar flow across the LVOT (flow velocity, 0.83 m/s; peak gradient, 2.8 mm Hg), and only a trace of mitral regurgitation was seen despite massive hypertrophy of the ventricular septum (Video clip 2, please see video loop available at www.anesthesia-analgesia.org). Several interesting echocardiographic findings in this patient could have accounted for this: 1) the basal segments were less hypertrophied than the rest of the ventricular septum, allowing the LVOT to remain open; 2) severe left ventricular dysfunction; 3) restricted MV leaflet motion of both, the anterior as well as the posterior, leaflets (Fig. 3) due to leaflet tethering caused by hypertrophy, and changes in ventricular geometry; and 4) hypertrophy of the posterior LV wall shifts the posterior annulus and posterior leaflet anteriorly, thus maintaining coaptation with the anterior leaflet.

View larger version (132K): [in this window] [in a new window]   Figure 3. Anatomic details of part of the posterior mitral valve (MV) leaflet including the subvalvular apparatus. Leaflet tethering caused severe restriction in posterior leaflet motion. The posterior MV leaflet is pulled apically leaving it almost immobile; the anterior leaflet is pulled apically and posteriorly. This restricted leaflet motion prevents the anterior leaflet from being pushed into the left ventricular outflow tract and allows leaflet coaptation with the posterior leaflet.

In summary, we present the intraoperative TEE findings in an unusual case of cardiomyopathy in a patient with Danon disease. Despite the massive cardiac hypertrophy, LVOT obstruction was not present due to the anatomic features discussed that were readily evaluated by intraoperative TEE.

Footnotes

Accepted for publication July 3, 2007.

This article has supplementary material on the Web site: www.anesthesia-analgesia.org.

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