(Vienna, 14 October 2026) Cardiac transthyretin amyloidosis (ATTR-CM) is a heart condition affecting older people that is being diagnosed with increasing frequency. A significant proportion of those affected also have mitral valve regurgitation. Until now, the severity of this condition has been assessed using cut-off values developed for patients with other forms of heart failure; a precise quantitative assessment, which is considered the gold standard for grading severity, has never been carried out for this clinical presentation because of the high effort it requires. An international research team led by MedUni Vienna has now carried out these measurements for the first time: on 1,101 patients from eight centres in four countries. The results, currently published in the leading journal "Circulation", show that the current cut-off values significantly underestimate the severity of mitral valve.
In order to develop disease-specific thresholds for assessing the severity of mitral valve regurgitation in cardiac amyloidosis, the research team led by Laurenz Hauptmann, Philipp E. Bartko and Christian Nitsche (Division of Cardiology, Department of Medicine II, MedUni Vienna) carried out quantitative measurements for the first time. The high relevance of these investigations stems from the specific conditions of blood flow in the heart associated with this condition: In cardiac transthyretin amyloidosis (ATTR-CM), misfolded proteins (transthyretin amyloids) are deposited in the heart muscle, causing the muscle to stiffen, restricting the filling of the heart chambers and significantly reducing the amount of blood the heart can pump into the circulation with each beat. Against this background, even a small volume of regurgitation through a leaky mitral valve has a significant impact, as it accounts for a substantial proportion of the already reduced stroke volume. As the study showed, the parameters currently specified in clinical guidelines significantly underestimate the severity of mitral regurgitation in patients with concomitant ATTR-CM, as they were predominantly developed for patients with other forms of heart failure.
The research team reached this conclusion following their investigations of 1,101 patients at eight specialist centres in Austria, Italy, Germany and the Netherlands: the mitral valve was assessed using standardised ultrasound examination of the heart (echocardiography). The analysis and measurement of the images according to disease-specific parameters (narrowest point of the regurgitant jet, size of the regurgitation orifice, volume and proportion of regurgitating blood) were carried out in a specialist laboratory at MedUni Vienna.
The findings show "that the volume of blood regurgitation carries far more weight in amyloid-infiltrated hearts, i.e. in ATTR-CM, than in the hearts on which the current threshold values were based," reports lead author Laurenz Hauptmann. "This can only be demonstrated through precise measurement, as we have carried out for the first time as part of this study."
The thresholds identified are well below the current guideline values: for example, a blood regurgitation volume of more than 38 millilitres per heartbeat was found to indicate a high risk of death and of hospital admission for heart failure, whereas the guidelines only assume severe mitral valve regurgitation from 45 millilitres upwards. Accordingly, under the new scheme, 21 per cent of patients were classified as high-risk, compared with 12 to 13 per cent under the previous definitions. "According to the standard criteria, roughly one in eight people is classified as severely affected; according to the disease-specific thresholds, it is one in five," said Hauptmann. "These patients have a measurably increased risk, but had not previously been identified as such."
The new scheme was also the only one that remained associated with mortality and hospital admission once age, comorbidities, renal function and medication were taken into account; the guideline definitions lost their predictive value.
"The data demonstrate that mitral valve regurgitation in ATTR amyloidosis requires its own, disease-specific criteria," emphasises Christian Nitsche, who co-led the study with Philipp E. Bartko. "This provides, for the first time, a robust basis for the further development of international guidelines and for the selection of those patients who could benefit from a procedure to treat mitral valve regurgitation." Patients with cardiac amyloidosis were excluded from previous large-scale studies on catheter-based mitral valve repair; the benefits of this procedure are currently being investigated in the randomised MILLENNIAL trial (NCT06075823), also led by Laurenz Hauptmann, Philipp E. Bartko and Christian Nitsche.
Publication: Circulation (Impact Factor 41.3)
Definition and Prognosis of Mitral Regurgitation in Transthyretin Amyloid Cardiomyopathy: A Multicenter International Cohort Study.
Laurenz Hauptmann, Christina Kronberger, Stéphanie K. Schwarting, Daniela Tomasoni, Lara S. Schlender, Sophia Koschatko, Maximilian Autherith, Charlotte Jantsch, Caglayan Demirel, Franz Duca, Andreas Kammerlander, Luca Bordignon, Gabriele Guidi Colombi, Nora Schwegel, Matteo Serenelli, Aldostefano Porcari, Steven A. Muller, Nicolas Verheyen, Marish I.F.J. Oerlemans, Maria Papathanasiou, Christian Hengstenberg, Marco Merlo, Jörg Hausleiter, Marianna Adamo, Philipp E. Bartko and Christian Nitsche.
DOI: 10.1161/CIRCULATIONAHA.125.079085
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.079085