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Dynamic left ventricular outflow tract (LVOT) obstruction is seen classically in hypertrophic cardiomyopathy. Cardiac amyloidosis can present with asymmetric hypertrophy that resembles hypertrophic cardiomyopathy, and, in some cases, with dynamic LVOT obstruction. The occurrence of syncope in such patients is not uncommon. The syncope is usually thought to be related to mechanisms other than LVOT obstruction, such as arrhythmias, conduction disturbances, orthostatic hypotension, or vasovagal effects associated with neuropathy.
Herein, we report the case of a patient who had immunocyte-derived (primary AL-type) cardiac amyloidosis with the echocardiographic appearance of hypertrophic cardiomyopathy and evidence of LVOT obstruction that caused syncope. We were able to provoke and identify dynamic LVOT obstruction that produced presyncopal symptoms similar to those that typically occur in such patients spontaneously. Dynamic LVOT obstruction as a cause of syncope should be considered in patients who have cardiac amyloidosis and echocardiographic evidence of hypertrophic cardiomyopathy.
The estimated age-adjusted incidence of immunocyte-derived (primary AL-type) amyloidosis is approximately 3,000 cases annually in the United States.1 Cardiac involvement is frequent and is the cause of death in at least 50% of affected patients.2 The most common echocardiographic findings include granular myocardial appearance, thickened ventricular walls, small cavities, the spectrum of diastolic dysfunction (from impaired relaxation to restrictive physiology), and, in advanced stages, systolic dysfunction.3–5 In a small percentage of patients (3%–5%), myocardial infiltration by amyloid has been reported to simulate hypertrophic cardiomyopathy (HCM) with asymmetric septal hypertrophy.6,7
Despite evidence of left ventricular outflow tract (LVOT) obstruction that is identified by documenting systolic anterior motion of the mitral valve,8 early systolic aortic valve closure,9 increase in LVOT flow velocity by continuous-wave Doppler echocardiography,10 and deterioration of hemodynamics after treatment with vasodilators,11 the occurrence of syncope in these patients has been attributed to mechanisms other than LVOT obstruction.12
We report here the case of a patient who had primary AL-type cardiac amyloidosis and syncope with echocardiographic evidence of HCM. We were able to provoke and identify dynamic LVOT obstruction that produced presyncopal symptoms similar to those that typically occur in such patients spontaneously.
In August 2006, a 69-year-old woman was admitted to our hospital for evaluation of syncope that had occurred repeatedly during mild physical activity. She had no major illnesses except for stage-1 essential systemic hypertension, for which she was under treatment with low-dose β-blockers and angiotensin-converting enzyme (ACE) inhibitors.
The most recent episode of syncope had lasted a few seconds, and it was preceded by dizziness and palpitations but not by aura phenomenon, tonic or clonic movements, or post-ictal state. She reported that similar episodes of dizziness and palpitations without loss of consciousness had occurred during the 6 months before her hospital admission.
The patient's initial vital signs were unremarkable, and there were no orthostatic blood pressure changes. The lungs were clear. The heart rate was normal and regular; however, there was a 2/6 systolic ejection murmur, best heard in the 2nd intercostal space at the left sternal border. The murmur increased in intensity upon performance of the Valsalva maneuver. Abdominal, neurologic, and musculoskeletal examinations revealed no abnormalities. There was trace pedal edema. The patient's laboratory values are listed in Table I.
An electrocardiogram, performed upon her hospital admission, revealed sinus rhythm and low voltage (Fig. 1). A 2-dimensional echocardiogram revealed marked asymmetric left ventricular hypertrophy of the basal septum, with a sigmoid shape protruding substantially into the LVOT, apical exclusion, and a submitral apparatus extending into the LVOT with systolic anterior motion in systole (Figs. 2 and and3).3). Biatrial enlargement was also noted. Doppler echocardiographic examination at baseline showed a mildly increased velocity across the LVOT (2 m/sec; gradient, 16 mmHg). During the Valsalva maneuver and after premature ventricular contractions (Fig. 4), the LVOT velocity increased dramatically (5 m/sec; gradient, 84 mmHg). The patient complained of dizziness and palpitations and requested that the test be stopped, because of her fear of losing consciousness. A right ventricular biopsy revealed the presence of significant interstitial amyloid deposits (Fig. 5) with positive immunohistochemistry for lambda light chains; this established the diagnosis of primary AL-type amyloidosis.
The patient had mild anemia, hyponatremia, hypokalemia, hypocalcemia, and hypoglycemia, along with marked hypoalbuminemia that was most likely secondary to multiorgan involvement, because it is frequently present in patients who have primary AL-type amyloidosis. We considered that these electrolytic abnormalities might have enhanced the frequency of premature ventricular contractions, which in turn, along with the vasodilation caused by ACE inhibitors, could have contributed to and aggravated the symptoms.
After the diagnosis was established, we corrected the patient's electrolytic abnormalities and continued treating her with β-blockers, but we discontinued her ACE inhibitors. Thereafter, no arrhythmias were noted during 96 hours of telemetry in the hospital. The patient refused chemotherapy. We discharged her in stable condition for outpatient follow-up. However, her functional status rapidly worsened, and heart-failure symptoms appeared in the ensuing weeks. She died 3 months after her discharge from the hospital.
The case of this patient illustrates an uncommon presentation of cardiac immunocyte-derived primary amyloidosis that simulates HCM along with evidence of dynamic LVOT obstruction and syncope. Cardiac amyloidosis, a diffuse myocardial infiltrative process, usually results in restrictive cardiomyopathy with impaired relaxation13 and myocardial dysfunction.14 However, a pattern of localized myocardial infiltration that resembles HCM has been reported in the medical literature in patients who have amyloidosis.6 In a similar manner, other infiltrative myocardial disorders, such as Fabry's disease, have been reported to have patchy myocardial infiltrate that resembles HCM.15,16
In patients with amyloidosis that resembles HCM, the variant of amyloid most commonly encountered is the senile (amyloid transthyretin) type17; only in a few patients is the AL type present.18 Recognition of the type of amyloid is important prognostically, because patients with AL amyloidosis often experience rapid and progressive cardiac dysfunction that portends an estimated average lifespan of less than 6 months. This contrasts with the familial and senile amyloidosis variants that are typically associated with milder clinical manifestations and slower progression of disease, and for which the reported average survival is 60 months.19,20
The occurrence of syncope in patients who have amyloidosis confers a poor prognosis. The causal mechanisms reported in the medical literature include arrhythmias, conduction disturbances, orthostatic hypotension, or vasovagal effects that are caused by neuropathy.21 As in our patient, dynamic LVOT obstruction can be an additional mechanism of syncope.
In the evaluation of patients who have amyloidosiswith syncope, we recommend specifically seeking echocardiographic evidence of HCM, and, if this is present, performing the Valsalva maneuver or other provocative tests. Identifying this novel hemodynamic cause of syncope is important therapeutically. First-line therapeutic interventions for HCM, such as β-blockers and calcium-channel blockers, are generally considered to be contraindicated in patients who have cardiac amyloidosis. However, a careful trial in patients who have amyloidosis and syncope secondary to LVOT obstruction might be beneficial. Also, myomectomy, a therapeutic alternative for patients with HCM, has been reported in a patient who had evidence of LVOT obstruction that was caused by senile amyloidosis; this treatment led to a successful long-term outcome.21
In conclusion, we believe that dynamic LVOT obstruction was the novel mechanism of syncope in our patient. Identifying this mechanism is important, because the treatment of such patients may differ from the treatments of cardiac amyloidosis patients who do not have HCM and LVOT obstruction.
Address for reprints: José-Luis E. Velazquez-Ceceña, MD, Department of Cardiology, Mount Sinai Hospital, California Avenue at 15th Street, Chicago, IL 60608. E-mail: moc.liamtoh@zeuqzalev;f5000x#&siulesoj