Longitudinal Trajectories of Secondary Mitral Regurgitation in Nonischemic Dilated Cardiomyopathy

Paolo Manca; Caterina Gregorio; Antonio De Luca; Carola Pio Loco; Massimiliano Mulè; Manlio Cipriani; Marco Merlo; Gianfranco Sinagra; Davide Stolfo

doi:10.1016/j.echo.2026.03.014

Longitudinal Trajectories of Secondary Mitral Regurgitation in Nonischemic Dilated Cardiomyopathy

J Am Soc Echocardiogr. 2026 Apr 4:S0894-7317(26)00140-9. doi: 10.1016/j.echo.2026.03.014. Online ahead of print.

Authors

Paolo Manca¹, Caterina Gregorio², Antonio De Luca³, Carola Pio Loco³, Massimiliano Mulè¹, Manlio Cipriani¹, Marco Merlo³, Gianfranco Sinagra³, Davide Stolfo⁴

Affiliations

¹ Department of Clinical Cardiology and Heart Failure, IRCCS ISMETT, Palermo, Italy; UPMC Italy, Palermo, Italy.
² Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
³ Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina, University of Trieste, Trieste, Italy.
⁴ Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina, University of Trieste, Trieste, Italy; Department of Medicine, Clinical Science and Education, Södersjukhuset Karolinska Institutet, Stockholm, Sweden. Electronic address: Davide.Stolfo@gmail.com.

PMID: 41941940
DOI: 10.1016/j.echo.2026.03.014

Abstract

Background: In nonischemic 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 [D], heart transplant [HT], left ventricular assist device implantation [LVAD]) associated with SMR trajectories were investigated.

Results: Secondary mitral regurgitation trajectories identified for patients with baseline no to mild SMR (n= 440) were no progression (76.2%), mild worsening (10.2%), and severe worsening (13.6%). In patients with baseline moderate to severe SMR (n= 324), trajectories included persistent moderate to 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 to severe SMR, any improvement of SMR was linked with a lower risk of D/HT/LVAD, whereas in patients with none to 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.

Keywords: Heart failure; Longitudinal trajectories; Non-ischemic dilated cardiomyopathy; Prognosis; Secondary mitral regurgitation.