This clinical case highlights the potential value of dobutamine stress echocardiography in anticipated low-grade true-severe AS. After the initial echocardiography showing low LVEF, a mean valvular gradient <40 mmHg and a calculated valve area <1 cm2, the patient was suspected to have low-flow, low-gradient aortic stenosis [3]. This disease entity would normally lead to valve replacement because of the potential benefits in terms of symptoms and survival gained from this procedure [3, 11], but should also be assessed very carefully when planning valve replacement. The American College of Cardiology recommends AVR for “symptomatic patients with severe AS and decreased systolic opening in calcified or congenitally stenotic aortic valves and an aortic velocity of >4.0 m/s or greater, or a mean pressure gradient of 40 mmHg or higher and symptoms of heart failure” [11]. However, in particular patients without contractile reserve have been shown to have exceedingly high operative mortality [12]. Differentiation between patients with low-flow, low-gradient stenosis and those with pseudo-severe stenosis can be very difficult in clinical practice since echocardiographic characteristics might differ only marginally at rest between both groups. Dobutamine stress echocardiography was first used as early as 1995 to distinguish these two subgroups. Based on the results from this study, it was already speculated that a broader use of this method might be clinically useful [13]. In 2001 it was first shown that clinical management of individuals with aortic stenosis and left ventricular dysfunction as well as low or intermediate valve gradients can indeed be improved by dobutamine stress echocardiography, because not only the distinction between patients with severe and non-severe aortic stenosis is improved, but this has indeed relevant implications on clinical outcome [14]. True-severe low-flow, low-gradient stenosis patients primarily benefit from AVR, since the valve itself is the main problem, whereas the primary pathology in pseudo-severe stenosis is located in the myocardium, requiring intensified conservative or specialized treatment based on the underlying disease [15].
In the present case, aortic stenosis of our patient could be clearly classified pseudo-severe by low dose dobutamine stress echocardiography. In the respective guidelines of the European Society of Cardiology, this procedure is not well established, but mentioned as potentially useful for the aforesaid diagnostic indication [3]. It is a widely-used, non-invasive method that can be done not only in-hospital but also in ambulatory patient care. Examination time is actually short and procedural risk has shown to be low [13]. Therefore, the net benefit greatly outweighs potential patient risks, justifying the investment in cases similar to the one described above.
Following stress-echocardiography, we performed cardiac MRI to reveal the origin of high-grade systolic dysfunction in our patient, revealing typical signs of an infiltrative cardiomyopathy such as late gadolinium enhancement [16] and dilated atria as well as a thickened septum and global left ventricular hypertrophy. High sensitive troponin was checked and turned out to be elevated. This serum biomarker has been shown to be a useful but non-specific diagnostic tool in various hereditary or secondary cardiomyopathies such as e.g. Sarcoidosis or Anderson-Fabry disease [17, 18]. In the described case, the final diagnosis ultimately clarifying the etiology of the pathological myocardial findings was made by endomyocardial biopsy from the right ventricle. Histological findings clearly revealed cardiac amyloidosis.
Amyloidosis is a systemic disease which can affect every organ, but especially cardiac involvement is a major determinant in patients prognosis [19]. In general, amyloidosis is considered a rare disease. However, there is a high probability of under-diagnosis particularly in elderly patients, where specific symptoms can be easily misinterpreted as an expression of advanced aging processes. Different studies have also shown that Amyloidosis and AS may occur together in a significant number of patients [20–23]. Today, several diagnostic tools are available to rule out whether a patient is indeed affected by cardiac amyloidosis, including the ECG, serum biomarkers, echocardiography, MRI and nuclear medicine imaging techniques [24, 25]. In cases where additional advanced imaging techniques are not available, standard echocardiographic examinations can be expanded by speckle tracking analysis of left ventricular (systolic) function [26]. However, in order to come to a definite diagnosis, current guidelines recommend endomyocardial biopsy [27]. Guidelines for therapy also recommend intensified heart failure therapy in respective patients with mainly systolic dysfunction. However, the impact of device therapy such as CRT-D on top of medical therapy on symptoms and prognosis in cardiac amyloidosis is currently not well investigated.
The presented case highlights some important aspects and pitfalls in diagnosis and treatment of elderly patients with aortic valve stenosis transferred to hospital for aortic valve replacement. While the natural history of low-gradient aortic valve stenosis and concept of optimum therapy including valve replacement is generally better understood today, great care has to be taken not to exaggerate these findings to patients with pseudo-severe aortic valve stenosis. Stress echocardiography should be considered part of the standard optimum diagnostic spectrum in all unclear or borderline cases in order to confirm the correct diagnosis and constitute optimal therapy.
