Publications

  • Patients implanted with the Carillon Mitral Contour System were evaluated for long‐term follow‐up post‐procedure up to 7.5 years.
  • Patients experienced a clinically significant reduction in heart failure hospitalizations and symptom improvement post procedure which was sustained through the 6+ year follow-up period.
  • Long-term mortality was 40% at 6 years, which compares favorably to several prior studies that have evaluated medically managed patients with FMR.

Patients treated with the Carillon device continue to show sustained improvements in mitral regurgitation, left ventricular volume, ejection fraction, and clinical status 6+ years post procedure. All patients at 6 year follow-up had MR 2+ or less with over half having MR 1+ or trace, and LVEDV was reduced from 154.0 ± 65.7 mL at baseline to 104.5 ± 59.2 mL (p=0.03).

This analysis brings new insights into the long-term role of the Carillon Mitral Contour system for the treatment of symptomatic congestive heart failure with functional mitral regurgitation.

A total of 74 patients from the TITAN, TITAN II and REDUCE FMR clinical studies who had symptomatic congestive heart failure despite guideline-directed medical therapy, grade 2+ to 4+ FMR, left ventricular enlargement, and reduced ejection fraction were assessed as part of the analysis. For all patients, echocardiographic parameters were available through the 12-month visit and vital status was available through 5 years.

  • Over 1 year of follow-up, the New York Heart Association (NYHA) class decreased in 64% of patients, distance on the 6-minute walk test increased, and echocardiographic measures indicated significant decreases in MR grade and favorable left ventricular remodeling.
  • The Kaplan-Meier survival rate was 83.6% at 1 year, 73.1% at 2 years, 67.9% at 3 years and 56.2% at 4 and 5 years of follow-up.
  • Primary determinants of long-term survival were a decrease in NYHA class, an increase in 6-minute walk test distance, and a decrease in regurgitant volume during the first year of follow-up.
  • Three-year mortality rate compared to published outcomes of COAPT and guideline directed medical therapy (GDMT), using matched patient populations, was 33.7% for Carillon, 42.8% for MitraClip in COAPT and 55.5% for GDMT.

  • First study to directly compare patients treated with either Carillon (n=37) or MitraClip (n=137).
  • MR grade was significantly reduced (p<0.001) in both groups after procedure.
    • MR grade remained reduced in Carillon patients at 2 years (n=9).
  • Survival was assessed up to 5 years.
    • Median survival in the Carillon group was 3.92 years vs 1.66 years in the MitraClip group (p = 0.01).
    • Numerous baseline factors may contribute to the difference in survival benefit observed.
  • Pulmonary artery pressure was reduced in both groups after intervention (p<0.05), however, continued decrease at later follow up was observed only in the Carillon group.

  • 37 patients implanted with the Carillon device were included in this retrospective, single-center study.
  • First study to show significant reduction in annular diameter in both anterior-posterior and anterolateral-posteromedial aspects (p<0.001) after any transcatheter mitral valve repair therapy.
  • Left atrial volume significantly reduced (p<0.02) at 30 days follow up and maintained through 1 year.

  • 30 patients with symptomatic moderate or severe SMR [FMR] were assessed for the acute effects of Carillon therapy by advanced echocardiography 1 day prior to procedure and at discharge.
  • Treatment of SMR [FMR] with the Carillon device leads to acute reduction of MR severity in 83% of patients after the procedure.
    • Both PISA based measurements of regurgitant volume as well as measurements derived from regurgitant fraction were significantly improved (p<0.05) after the procedure.
  • Effective [forward] stroke volume was significantly improved (p<0.001) and ejection fraction was non-significantly improved (p = 0.06) immediately after the intervention.

This study showed that potential coronary artery compromise can be managed safely and effectively in all patients with 95% successfully implanted.

  • 17 patients were implanted with the Carillon device in a prospective, single-center, non-randomized study.
  • Patients experienced a mean one grade reduction of MR acutely (2.8 to 1.9, p<0.005) with an additional improvement at 3 months (1.5, p<0.005).
  • In 41.2% of patients an acute reduction of coronary artery flow was detected intraoperatively and in all except one patient this could be easily managed such that the patients successfully received the implant.

This analysis showed that Carillon addresses FMR and, in as little as one-month, successful implantation results in left ventricular reverse remodelling and increased systolic performance. Mitral tenting area is an important baseline parameter in predicting treatment efficacy with Carillon.

  • 35 patients were enrolled and 22 were successfully implanted with the Carillon device. Some patients were not implanted due to coronary sinus size (n=3), impaired access (n=2), compromised coronary flow (n=4), or insufficient mitral regurgitation reduction (n=4).
  • At one-month follow-up, statistically significant reductions in the following parameters were observed: anteroposterior (AP) diameter, regurgitant volume (RV), vena contracta (VC), effective regurgitant orifice area (EROA), proximal isovelocity surface area (PISA), mitral tenting area, mitral tethering, and mean diastolic interpapillary distance.
  • Patients with increased left atrial diameters saw greater improvement in ejection fraction, following implantation.

In patients with severe heart failure and mitral regurgitation, Carillon can be successfully used as a first line medical device intervention.

  • Case report of a NYHA class IV patient who presented with severe dyspnea progressing to orthopnea and paroxysmal nocturnal dyspnea. He was found to have severe functional mitral regurgitation Grade 4 and severe left ventricle systolic dysfunction. Surgical mitral intervention was not considered suitable and percutaneous mitral annuloplasty was performed with Carillon Mitral Contour System.
  • From baseline to 6-months following implantation of Carillon the patient experienced a 70% reduction in vena contracta (0.25cm vs. 0.84cm), 90% reduction in regurgitant volume (29ml vs. 291ml). MR Grade was reduced from a grade 4 to grade 2 and NYHA class improved from IV to I.
  • Remodelling of the left ventricle was observed and resulted in an absolute improvement in ejection fraction of 30% (from 20% to 50%).
  • The patient’s symptoms improved so significantly that he was no longer considered an immediate candidate for CRT.

Carillon increased functional capacity and improved echocardiographic parameters in FMR patients.

  • This study enrolled 14 consecutive patients who underwent Carillon implantation.
  • Echocardiographic parameters, 6MWD, Naughton treadmill exercise test, NYHA class and QOL were assessed at baseline and after one month.
  • All measurements demonstrated statistically significant improvement at one month from baseline.
  • Echocardiographic MR parameters were observed immediately after the procedure and during the one month follow up; these parameters included vena contracta (0.36cm after procedure and 0.31cm at one month vs. 0.65cm at baseline, both p<0.001) and effective regurgitant orifice area (0.18cm2 after procedure and 0.20cm2 at one month vs. 0.28cm2 at baseline, p<0.05 and p<0.005, respectively).
  • One month after the procedure the 6MWT (25%, p<0.001), Naughton treadmill exercise test (45.0%, p<0.005) and NYHA classifications (34.1%, p<0.005) were significantly improved.

Carillon improved echocardiographic parameters in functional mitral regurgitation patients.

  • In this study, nine patients were enrolled and successfully implanted with the Carillon device.
  • One-month post-implant, vena contracta, the ratio of the jet area to the left atrial area, and other echocardiographic parameters were assessed relative to baseline.
  • Vena contracta and jet area to left atrial area improved (p<0.05 and p<0.005, respectively).

This study showed that percutaneous mitral valve repair may be cost-effective in patients with FMR due to heart failure.

  • Cost-utility analysis of Carillon Mitral Contour System was performed based on the TITAN trial results using a combination of a decision tree and Markov process. The analysis was performed from the German statutory health insurance perspective over 10-year time horizon.
  • Carillon provided additional benefits to patients with an 1.15 incremental quality-adjusted life years (QALY) and an 1.41 incremental life years. The procedure was cost-effective in comparison to optimal medical therapy (OMT) with an incremental cost-effectiveness ratio of €15,533/QALY. With a willing- ness-to-pay threshold of €35,000/QALY, PMVR had a 84% probability of being cost-effective.

Carillon can be implanted prior to CRT and may provide additional benefit to HF patients with FMR, low ejection fraction and wide QRS.

  • Case study of a 45-year-old male with ischemic heart failure who underwent successful implantation of a Carillon device.
  • The procedure resulted in clinical improvements and a decrease in FMR.
  • Fifteen months post implant, the patient was a candidate for CRT and underwent successful implantation, which resulted in further improvement of clinical and echocardiographic parameters.

It is possible to implant the Carillon device prior to a CRT device in HF patients with low ejection fraction, wide QRS and FMR.

  • Three patients meeting current guidelines for cardiac resynchronization therapy (CRT) included in the AMADEUS trial underwent CRT implantation 7-8 months after implantation of a mitral valve annuloplasty device.
  • Access to the coronary sinus and placement of the left ventricular lead into a posterolateral cardiac vein was not at all compromised by the mitral valve annuloplasty device in any patient.

  1. Lipiecki, J, Fahrat, H, Séverine, M, et al. Long-term prognosis of patients treated by coronary sinus-based annuloplasty: single centre experience. ESC Heart Failure. October, 2020.
  2. Lipiecki, J, Kaye DM, Witte KK, et al. Long-Term Survival Following Transcatheter Mitral Valve Repair: Pooled Analysis of Prospective Trials with the Carillon Device. Cardiovascular Revascularization Medicine. February, 2020.
  3. Stephan Heyl, Aria Nikkhoo, Markus Wieszner, Stephan Fichtlscherer, Florian Seeger, Birgit Assmus, Brigitte Luu, Katrin Hemmann, Claudia Walther, Joerg Honold. Comparison of effectiveness and survival after the MitraClip or Carillon procedure for severe functional mitral regurgitation: a single-center retrospective analysis. Arch Med Sci Atheroscler Dis. June, 2020.
  4. Tobias Friedrich Ruf, Felix Kreidel, Alexander Robert Tamm, Martin Geyer, Omar Hahad, Julia Claudia Zirbs, Ben Luca Schwidtal, Andres Beiras-Fernandez, Klaus K. Witte, Thomas Münzel, Ralph Stephan von Bardeleben. Transcatheter indirect mitral annuloplasty induces annular and left atrial remodelling in secondary mitral regurgitation. ESC Heart Failure. April, 2020.
  5. Stephan Stöbe, Kristin Kreyer, Daniel Jurisch, Dietrich Pfeiffer, Daniel Lavall, Gerardo Farese, Ulrich Laufs, Andreas Hagendorff. Echocardiographic analysis of acute effects of percutaneous mitral annuloplasty on severity of secondary mitral regurgitation. ESC Heart Failure. May, 2020.
  6. Klein, N. et al. Mitral Annuloplasty Device Implantation for Non-Surgical Treatment of Mitral Regurgitation: Clinical Experience after the Approval Studies. Journal of Invasive Cardiology. February, 2016.
  7. Kałmucki P., Jerzykowska O., Dankowski R., Baszko A., Kramer L., Szyszka A., Siminiak T. Percutaneous Trans-Coronary Venous Mitral Annuloplasty in Patients With Functional Mitral Regurgitation: Analysis of Poznan Carillon Registry Data. J Interv Cardiol. 2016.
  8. Soofi, M.A., Alsamadi F. Restoration of Normal Left Ventricular Geometry after Percutaneous Mitral Annuloplasty: Case Report and Review of Literature. Catheterization and Cardiovascular Interventions. 2014.
  9. Woloszyn M, Jerzykowska O, Kałmucki P, Lunk R, Firek L, Kuzemczak M, Siminiak T. Functional assessment of patients after percutaneous mitral valvuloplasty with Carillon device: a preliminary report. Kardiol Pol. 2011;69(3):228-33.
  10. Jerzykowska O, Kalmucki P, Woloszyn M, Smuszkiewicz P, Firek L, Siminiak T. Echocardiographic evaluation of percutaneous vavle repair in patients with mitral regurgitation using the Carillon system. Kardiol Pol. 2010;68(1):57-63.
  11. Borisenko, O., Haude, M., Hoppe, UC., Siminiak, T., Lipiecki, J., Goldberg, S., Mehta, N., Bouknight, O., Bjessmo S., Reuter DG. Cost-utility analysis of percutaneous mitral valve repair in inoperable patients with functional mitral regurgitation in German settings. BMC Cardiovascular Disorders. 2015;15:43.
  12. Siminiak T, Jerzykowska O, Kałmucki P, Link R, Baszko A. Cardiac resynchronization therapy after percutaneous trans-coronary-venous mitral annuloplasty. Kardiol Pol. 2013;71(12):1293-4.
  13. Hoppe UC, Brandt MC, Degen H, Dodos F, Schneider T, Stoepel C, Kroener A, Haude M. Percutaneous mitral annuloplasty device leaves free access to cardiac veins for resynchronization therapy. Catheter Cardiovasc Interv. 2009;74(3):506-11.