**5.1 Amyloidosis misdiagnosed as a coronary artery or heart valve disease**

Unsuspected cardiac amyloidosis as a cause of sudden fatal circulatory collapse in the course other cardiological or surgical intervention has been reported rather early (Goldman and Legnami 1966; Lindholm and Wick 1986; Kotani, Hashimoto et al. 2000; Wang and Pollard 2000). Postmortem examination in these case reports usually reveals surprisingly advanced stage of structural damage of the myocardium by amyloid deposits. Striking disparity between the gross morphological alteration and paucity of both clinical signs and diagnostic findings underlines the obvious difficulties of proper management strategies in cardiac amyloidosis.

Fatal response of the amyloidotic myocardium to the insult conveyed by anesthesia, general or cardiac surgery can be explained by concurrence of various pathophysiology mechanisms. Potential dysbalance of circulating volume in reaction to administration of anesthetic drugs cannot be adequately compensated in restrictive cardiomyopathy. Vicious circle is further potentiated by the myocardial inability to increase its contractile performance as well as by diffuse myocardial ischemia and susceptibility to arrhythmias. Standard treatment options, pharmacological support or counterpulsation, usually fail to resolve the circulatory shock.

In recent era of high volume cardiac surgery, the risk of referral of cardiac amyloidosis misdiagnosed for coronary or valve disease for cardiac surgery operation keeps to be present despite current improvements in diagnostic process. Obvious difficulties in proper diagnosis making of cardiac amyloidosis are combined with systemic bias of routine clinical thinking. Patient´s symptoms that are indicative of far more prevalent diagnoses, namely coronary artery disease, prompt to perform coronarography. Though not typical for cardiac amyloidosis, stenoses of epicardial coronary arteries can either be clearly present on coronarography or at least stenoses of some degree may be assumed as a sufficient explanation of angina symptoms. Once labeled as patients with coronary artery disease a routine echocardiography is usually performed with focus on systolic ventricular function and presence of mitral regurgitation. When cardiac hypertrophy is not strikingly present diastolic dysfunction can be easily overlooked or not taken into account.

Fatal outcome of coronary artery bypass grafting in misdiagnosed patients with cardiac amyloidosis has been reported by several authors (Massoudy, Szabo et al. 2003; Massias, Vyssoulis et al. 2006; Zacek, Medilek et al. 2007). In our institutional records (unpublished data) there were four fatal cases of undiagnosed cardiac amyloidosis indicated for coronary surgery (3x) or mitral and tricuspid valve repair (1x) (Fig. 1). In 3 ischemic patients, however, only two had debatable coronary stenoses while the third had a severe left main stenosis. Echocardiography was undiagnostic in all three of them. Postmortem microscopy revealed advanced stage of cardiac amyloidosis also with documented obliterative deposition of amyloid in small coronary vessels (Fig 2). The echocardiography of the patient

Cardiac surgery, in logical consequence of low prevalence of cardiac amyloidosis, difficult straightforward diagnostics and very limited scope of action due to the nature of the disease, has a relatively small window of experience. Majority of the authors have published anecdotic case reports and only data on transplanted patients accumulate the evidence from small cohorts. Basically, there are three clinical pathways in which a patient with cardiac

Unsuspected cardiac amyloidosis as a cause of sudden fatal circulatory collapse in the course other cardiological or surgical intervention has been reported rather early (Goldman and Legnami 1966; Lindholm and Wick 1986; Kotani, Hashimoto et al. 2000; Wang and Pollard 2000). Postmortem examination in these case reports usually reveals surprisingly advanced stage of structural damage of the myocardium by amyloid deposits. Striking disparity between the gross morphological alteration and paucity of both clinical signs and diagnostic findings underlines the obvious difficulties of proper management strategies in

Fatal response of the amyloidotic myocardium to the insult conveyed by anesthesia, general or cardiac surgery can be explained by concurrence of various pathophysiology mechanisms. Potential dysbalance of circulating volume in reaction to administration of anesthetic drugs cannot be adequately compensated in restrictive cardiomyopathy. Vicious circle is further potentiated by the myocardial inability to increase its contractile performance as well as by diffuse myocardial ischemia and susceptibility to arrhythmias. Standard treatment options, pharmacological support or counterpulsation, usually fail to

In recent era of high volume cardiac surgery, the risk of referral of cardiac amyloidosis misdiagnosed for coronary or valve disease for cardiac surgery operation keeps to be present despite current improvements in diagnostic process. Obvious difficulties in proper diagnosis making of cardiac amyloidosis are combined with systemic bias of routine clinical thinking. Patient´s symptoms that are indicative of far more prevalent diagnoses, namely coronary artery disease, prompt to perform coronarography. Though not typical for cardiac amyloidosis, stenoses of epicardial coronary arteries can either be clearly present on coronarography or at least stenoses of some degree may be assumed as a sufficient explanation of angina symptoms. Once labeled as patients with coronary artery disease a routine echocardiography is usually performed with focus on systolic ventricular function and presence of mitral regurgitation. When cardiac hypertrophy is not strikingly present

Fatal outcome of coronary artery bypass grafting in misdiagnosed patients with cardiac amyloidosis has been reported by several authors (Massoudy, Szabo et al. 2003; Massias, Vyssoulis et al. 2006; Zacek, Medilek et al. 2007). In our institutional records (unpublished data) there were four fatal cases of undiagnosed cardiac amyloidosis indicated for coronary surgery (3x) or mitral and tricuspid valve repair (1x) (Fig. 1). In 3 ischemic patients, however, only two had debatable coronary stenoses while the third had a severe left main stenosis. Echocardiography was undiagnostic in all three of them. Postmortem microscopy revealed advanced stage of cardiac amyloidosis also with documented obliterative deposition of amyloid in small coronary vessels (Fig 2). The echocardiography of the patient

diastolic dysfunction can be easily overlooked or not taken into account.

**5.1 Amyloidosis misdiagnosed as a coronary artery or heart valve disease** 

**5. Cardiac surgery in cardiac amyloidosis** 

amyloidosis may be referred for cardiac surgery:

cardiac amyloidosis.

resolve the circulatory shock.

Fig. 1. Marked myocardial hypertrophy 610 g) in 75-year-old patient indicated for coronary artery bypass grafting for hemodynamically significant left main stem stenosis. Type of cardiac amyloidosis not identified (negative for AL, AA and senile amyloidosis). Besides presyncope in patient history no relevant data indicative of possible presence of amyloidosis were traced.

indicated for mitral and tricuspid surgery displayed no clear indications of amyloid restrictive cardiomyopathy even on retrospective reevaluation.

From the published data there is evident lack of constant and specific signs that could reroute in real world the misdiagnosis in process and avoid disastrous and unjustified cardiac operation. Low QRS voltage seems to be very constant but of low specificity. Interestingly, constant is the surgeon´s immediate tactile recognition of rubbery, stiff and nodular surface of myocardium. In obvious absence of diagnostic pattern that can safely indicate the correct diagnosis of cardiac amyloidosis the only advice is, first, meticulously include in consideration all the available data from patient history and examination, and, second, be sensitive for "small discrepancies" between the symptoms and objective findings (e.g., two of our patients had no clear angina but an effort dyspnea and fatigue were taken as an equivalent of this in presence of moderate stenoses on coronarography).

Correct diagnosis of cardiac amyloidosis would prevent disastrous outcome of bypass surgery in case of insignificant involvement of epicardial coronary arteries. Contrary to this, coincidence of severe coronary disease coinciding with amyloid disease will necessitate

Fig. 2. Obstructive amyloid deposits in the wall of small intramyocardial artery (hematoxyllin-eosin, 400x)

percutaneous coronary intervention even in a difficult topography, instead of a surgery. Severe valve disease in a known cardiac amyloidosis would most probably lead to decision for conservative treatment.
