Non-Interventional Study on the Prevalence of Cardiac Amyloidosis in Patients With Higher-Grade Aortic Valve Stenosis - Evaluation Using Echocardiography, Computed Tomography, Tc99-SPECT/CT and Cardiac Magnetic Resonance Imaging (CMR)

Degenerative aortic valve stenosis (AS) is currently the most common heart valve disease in western countries. It is defined as aortic valve opening area <1.0cm² and/or an average gradient of 40mmHg. Elderly patients with higher-grade AS are primarily treated interventionally by means of transcatheter aortic valve implantation (TAVI). The outcome here does not seem to be any worse compared to conventional/cardiac aortic valve replacement. A hallmark of higher grade AS is left ventricular hypertrophy. In addition, there is often a restrictive filling pattern, which can be demonstrated in echocardiography. These characteristics are also found in cardiac amyloidosis of the TTR type (transthyretin type). Amyloid was found in over 70% of surgically removed heart valves in patients who received an aortic valve replacement. The detection of amyloid is of clinical importance for the patient, since there are different therapeutic approaches depending on the respective amyloid form. Endomyocardial biopsy (EMB) is currently the gold standard for the detection of cardiac amyloidosis in many places. However, it is an invasive procedure with associated risks and limitations (e.g. sampling error). Cardiac amyloidosis can be recognized non-invasively by the calcium-associated storage of technetium 99m (Tc99m)-labelled phosphonates, as is traditionally used in skeletal scintigraphy. According to the previous data, Tc99m phosphonate scintigraphy using SPECT/CT has a high specificity for the detection of TTR amyloidosis. If a SPECT/CT is available, this non-invasive diagnostic procedure is preferred to EMB.

The previous data indicate a correlation between the prognosis and the phosphonate storage in the myocardium. Using the Perugini score, the tracer uptake is only classified as a discrete size in a rough grid. A quantification of myocardial radiopharmaceutical intake could provide quantitative parameters that not only better reflect the severity of cardiac amyloidosis, but could also serve as a prognostic parameter. Such a quantification could take place through hybrid imaging using SPECT/CT, in which the anatomical information from computer tomography (CT) is combined with the functional information from single photon emission tomography (SPECT). This quantification takes place in a post-processing of the acquired data sets.

In addition to Tc99-SPECT/CT, cardiac MRI (CMR) with its excellent tissue characterization can also display inflammatory and fibrotic changes in the heart muscle, as can occur in amyloidosis as part of protein deposition. In addition to the established late gadolinium enhancement (LGE) technique, which can primarily map focal fibrotic processes with high accuracy, current CMR techniques for tissue characterization (T1/T2 mapping) can also be used to quantify diffuse myocardial changes, and distinguish fibrotic from inflammatory changes of the heart muscle by T1 or T2 weighting. If the Tc99-SPECT/CT findings are noticeable, a subsequent CMR is carried out for verification at the UKT as standard. This is the case in approximately 10% of patients.

If early detection of cardiac amyloidosis is assured, the clinical course of the patient could possibly be positively influenced by timely adequate therapy.

The aim of this study is to first determine the prevalence of cardiac amyloidosis using SPECT/CT and, if available, to quantify it. In patients with conspicuous SPECT/CT, the multimodal CMR is then (still) more likely to make possible cardiac amyloidosis as a second non-invasive method. The standardized follow-up after 6 or 12/24 months is planned to check the parameters determined by imaging technology (Tc99-SPECT/CT (or CMR)) for their prognostic relevance.

Inclusion criteria

• Patients with severe aortic valve stenosis (valve opening area <1 cm², pmean >40 mmHg, Vmax >4 m/sec)
• Suspected cardiac amyloidosis
• Performance of one or more of the following imaging examinations due to (justifiable) clinical indication: echocardiography, photon-counting computed tomography (CT), Tc99-SPECT/CT, cardiac MRI
• Age ≥18 years
• Written consent of the patient for prospective data collection regarding Tc99-SPECT/CT, CT, and, if applicable, CMR and follow-up

Exclusion criteria

• patients unable to give consent