1Deutsches Herzzentrum der Charite (DHZC) Berlin, Deutschland; 2Institute of biometry and clinical epidemiology (iBikE), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin, Deutschland; 3Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin, Deutschland; 4Universitätsklinikum Frankfurt Med. Klinik III - Kardiologie, Angiologie Frankfurt am Main, Deutschland; 5Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik für Neurologie und Experimentelle Neurologie Berlin, Deutschland; 6Sana Klinikum Lichtenberg Klinik für Innere Medizin II, Schwerpunkt Kardiologie Berlin, Deutschland
Background: Patients with aortic valve stenosis (AS) commonly suffer from additional cardiac amyloidosis (CA). The concomitant occurrence of both diseases leads to a relevant increase in morbidity and mortality. However, due to similar clinical presentations, CA in AS is often overlooked. The present SAVER study (Screening for Amyloidosis before Aortic Valve Elective Replacement) aimed to develop a CA screening tool for AS patients in daily clinical practice.
Methods: AS patients with an age of at least 40 years who underwent surgical (SAVR) or transcatheter aortic valve implantation (TAVI) were enrolled in the multicenter, prospective cohort trial. Exclusion criteria comprised New York Heart Association (NYHA) class IV, redo-TAVI or -SAVR, ongoing chemotherapy, bicuspid AS in patients younger than 70 years, and patients who were unable to consent. The CA screening approach was based on current literature and recommendations and comprised of a CA-specific patient questionnaire as well as clinical and paraclinical parameters assessed in clinical routine. In case of four or more positive findings, patients were recommended to undergo a bone scan or a magnetic resonance imaging (MRI).
Results: A total of 1002 patients were enrolled in the study. Most of the patients were male (58%) and had a median age of 81 (76-84) years. TAVI was implanted in 85%, whereas SAVR was performed in 15% of cases. According to the SAVER screening tool, 41% of patients exhibited signs of concomitant CA. These patients were older and, accordingly, more frequently experienced TAVI than SAVR. 49% of patients with suspected CA underwent the recommended bone scan. A Perugini Score ≥1 was observed in 15 patients (7,5%). Compared to patients with a Perugini Score of 0, those with a Perugini Score ≥1 more frequently reported a bilateral carpal tunnel syndrome, spinal stenosis, increase of the tongue, and numbness in the arms and legs. Patients with a Perugini Score ≥1 had a higher occurrence of N-terminal prohormone of brain natriuretic peptide (NTproBNP) levels >4000png/ml, troponin T (TnT-hs) levels ≥40pg/ml, and right bundle branch block. Echocardiographic examinations prior to TAVI or SAVR revealed a higher prevalence of patients with sparkling myocardium and diastolic dysfunction (E/E`>20) in patients with a Perugini Score ≥1. Further parameters that did not exhibit a clear trend as indicators for CA comprised hands, that fall asleep, polyneuropathy, unsteady gait, biceps tendon rupture, gastrointestinal complaints, new atrial hypotension, atrial fibrillation, implanted pacemaker, left and right ventricular wall thickening, interatrial wall thickening, apical sparing, global longitudinal strain >-10%, mean pressure gradient across the aortic valve <40mmHg pericardial effusion, reduced mitral annular plane systolic excursion (MAPSE), low-voltage, and Sokolow-Lyon-index <1.9mV in ECG. Five patients (2%) without and one patient with Perugini Score ≥1 (11%) had a monoclonal gammopathy of undetermined significance or a plasmacytoma.
Conclusion: The presented SAVER study established an easy tool to screen for ATTR-CA in AS in daily clinical practice. Indicators for a Perugini Score ≥1 comprised bilateral carpal tunnel syndrome, spinal stenosis, numbness in arms and legs, elevated NTproBNP and TnT-hs levels, a right bundle branch block, sparkling myocardium, and diastolic dysfunction.