A 59-year-old male presented with worsening dyspnea and orthopnea over the past five months. A review of systems revealed anorexia and an unintentional 40-pound weight loss over the past year. The patient has also been hospitalized six months prior after presenting with right-sided weakness and facial droop, and was found to have a left temporal and basal ganglia cerebrovascular accident (CVA).
Physical examination findings were consistent with fluid overload: jugular venous distention, decreased breath sounds at the right base up to the mid lung field, pulsatile liver and 1+ bilateral lower extremity pitting edema. Laboratory studies identified an elevated brain natriuretic peptide of 512 pg/mL and troponin I of 0.40 with normal total creatine kinase. Chest radiograph revealed cardiomegaly and a moderate-sized right pleural effusion (Figure 1). Electrocardiogram demonstrated sinus rhythm with a first-degree arteriovenous (AV) block, low voltage in limb leads, and Q-waves in anterior and inferior leads (Figure 2).
The patient was initially diuresed and then underwent a right and left heart catheterization to evaluate the etiology of newly diagnosed congestive heart failure. Left heart catheterization demonstrated non-obstructive coronary artery disease and elevated left ventricular end-diastolic pressure (17 mmHg). Right heart catheterization was markedly abnormal, with elevated right atrial pressures (mean 12 mmHg) with prominent Y descent (Figure 3); dip-and-plateau (“square root sign”) right ventricular tracing (Figure 4) with an elevated end-diastolic pressure (11 mmHg); elevated pulmonary artery systolic pressure (36 mmHg); and elevated pulmonary capillary wedge pressure (17 mmHg). These findings prompted an echocardiogram, which revealed increased left ventricular myocardial thickness with speckled appearance (Figure 5); moderate global hypokinesis; biatrial dilatation with elevated right atrial pressure; and diminished mitral annular E velocities suggestive of a restrictive cardiomyopathy. Abdominal fat biopsy was later performed, but the pathology was indeterminate. Subsequently, right ventricular biopsy was performed using an 8 French RVB guide and bioptome (Cordis Corporation) with four samples taken from the mid-right ventricular septum. Pathology demonstrated birefringent material under polarized light with Congo red stain and interstitial fibrosis, confirming the diagnosis of amyloidosis.
Amyloidosis is a deposit of fibrils composed of various serum proteins that can result in a restrictive cardiomyopathy. It may be classified as primary amyloidosis when caused by a plasma cell defect resulting in deposition of immunoglobulin light chain proteins, or secondary amyloidosis when associated with other illnesses resulting in accumulation of amyloid fibrils. Cardiac involvement is common in primary amyloidosis, where it is the predominant manifestation in about one-third of patients, leading to progressive left ventricular dysfunction and conduction disease.1 Amyloid infiltrates the atria as well, causing electromechanical dysfunction of the atrium during sinus rhythm, which can predispose atrial thrombi. A report of 116 autopsy or explanted cardiac amyloidosis cases identified intracardiac thrombi in 33% of amyloid hearts.2 Ischemic stroke occurs in some patients with amyloidosis, although the incidence is not well defined. Of forty patients with primary AL and ischemic stroke evaluated at the Mayo Clinic from January 2000 to July 2006, ischemic stroke was the initial presentation in 33% of patients, preceding a pathological diagnosis of amyloidosis by a mean of 9.6 months.3 History, physical examination, electrocardiography and echocardiography are key elements in evaluating amyloid cardiomyopathy but are not confirmatory in the diagnosis of cardiac amyloidosis. Endomyocardial biopsy demonstrating apple-green birefringence using Congo red stain is the gold standard for diagnosing amyloidosis.4 Endomyocardial biopsy has been proven to be safe and effective, with diagnostic accuracy approaching 100% with a minimum of four biopsy specimens5, although rare cases of biopsy-negative amyloid cardiomyopathy have been reported.6 Treatment is usually ineffective and generally consists of symptomatic and supportive measures. Chemotherapy and device therapy have shown limited or no benefit.7 Heart transplantation is not generally accepted as a viable treatment due to vast majority of patients having noncardiac amyloidosis, leading to disease progression or recurrent amyloidosis in the transplanted heart.8 It is therefore not surprising that median survival in amyloidosis has been reported to be 6-9 months in those with heart failure and 1.1 years in those with any sign of cardiac involvement.9
Herein, we report a rare case of cardiac amyloidosis diagnosed primarily based on cardiac catheterization findings, illustrating the importance of accurate interpretation of hemodynamic tracings in the appropriate clinical setting.
Dr. George can be contacted at: firstname.lastname@example.org.
Disclosure: Dr. George reports he is a consultant for Boston Scientific Corporation. Dr. Hakimi and Dr. Luft report no conflicts of interest regarding the content herein.
- Falk RH, Skinner M. The systemic amyloidosis: an overview. Adv Intern Med 2000;45:107-137.
- Feng D, Edwards WD, Oh JK, Chandrasekaran K, et al. Intracardiac thrombosis and embolism in patients with cardiac amyloidosis. Circulation 2007 Nov 20;116(21):2420-2426.
- Zubkov AY, Rabinstein AA, Dispenzieri A, Wijdicks EF. Primary systemic amyloidosis with ischemic stroke as a presenting complication. Neurology 2007 Sep 11;69(11):1136-1141.
- Cooper LT, Baughman KL, Feldman AM, Frustaci A, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol 2007 Nov 6;50(19):1914-1931.
- Pellikka PA, Holmes DR Jr, Edwards WD, Nishimura RA, Tajik AJ, Kyle RA. Endomyocardial biopsy in 30 patients with primary amyloidosis and suspected cardiac involvement. Arch Intern Med 1988 Mar;148(3):662-666.
- George JC, Katrapati P, Fang J. An unusual case of biopsy-negative amyloid cardiomyopathy. Congest Heart Fail 2010 Jan-Feb;16(1):39-41.
- Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm 2008 Feb;5(2):235-240.
- Hosenpud JD, DeMarco T, Frazier OH, Griffith BP, et al. Progression of systemic disease and reduced long-term survival in patients with cardiac amyloidosis undergoing heart transplantation. Follow-up results of a multicenter survey. Circulation 1991 Nov;84(5 Suppl):III338-III343.
- Dubrey SW, Cha K, Anderson J, Chamarthi B, et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM 1998 Feb;91(2):141-157.