Available online 4 April 2026

Author links open overlay panelPaolo Manca MD 1 2, Caterina Gregorio MD 3, Antonio De Luca MD 4, Carola Pio Loco MD 4, Massimiliano Mulè MD, PhD 1 2, Manlio Cipriani MD 1 2, Marco Merlo MD 4, Gianfranco Sinagra MD 4, Davide Stolfo MD, PhD 4 5Show moreHighlights•

Three SMR trajectories were identified in NICM across baseline severities.

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Most with moderate-severe SMR improved during long-term follow-up.

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Small left atrium and no LBBB were related to SMR improvement.

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Any improvement in SMR was associated with better prognosis;.

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Only severe worsening of SMR was related to worse outcomes;.

AbstractBackground

In non-ischemic dilated cardiomyopathy (NICM), the severity of secondary mitral regurgitation (SMR) is dynamic, depending on loading conditions and the effect of guideline-directed medical therapy (GDMT). However, the longitudinal trajectories of SMR and their prognostic implications remain insufficiently explored. We aimed to define the long-term trajectories of SMR and their prognostic impact in NICM.

Methods

We retrospectively analyzed 764 NICM patients who underwent serial echocardiographic evaluations over a median follow-up of 9 (4-15) years. The longitudinal trajectories of SMR were identified using a latent class mixed model. Phenotypic characteristics and cardiovascular outcomes (all-cause death, heart transplant, left ventricular assist device implantation – D/HT/LVAD) associated with SMR trajectories were investigated.

Results

SMR trajectories identified for patients with baseline no-mild SMR (n=440) were: no progression (76.2%), mild worsening (10.2%), and severe worsening (13.6%). In patients with baseline moderate-severe SMR (n=324), trajectories included persistent moderate-severe SMR (24%), mild improvement (8%), and strong improvement (68%). Smaller left atrium was associated with both mild and strong SMR improvement, while absence of left bundle branch block and New York Heart Association functional class <III were respectively associated with strong and mild SMR improvement. No independent factors related to SMR worsening were identified. In patients with baseline moderate-severe SMR, any improvement of SMR was linked with a lower risk of D/HT/LVAD, whereas in patients with none-mild baseline SMR only severe worsening was associated with higher risk of D/HT/LVAD.

Conclusions

Identification and characterization of longitudinal SMR trajectories may predict the outcome of individual patients with NICM and guide early therapeutic or interventional strategies to improve prognosis.

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2026 Published by Elsevier Inc. on behalf of the American Society of Echocardiography.