Publications
Long-term Survival Publications
Global Cardiology
Janusz Lipiecki, Piotr Kalmucki, Larry E. Miller, Nicolas Durel
July 2026
A single-center extension of the REDUCE FMR trial provides the longest known follow-up for any transcatheter mitral repair therapy.
- Ten-year cardiovascular survival was 66% demonstrating long-term durability and treatment impact in an advanced heart failure population
- Median survival was 5.6 years in an elderly and high-risk FMR population
- Predictors of long-term outcomes included baseline LVEF less than 35% and early heart failure hospitalization
THT 2025 Symposium Presentation
Witte
2025
A multi-center, real-world study of up to 500 patients treated with the Carillon Mitral Contour System as standard of care.
Interim analysis of 228 prospective and retrospective patients with up to 5 years of follow-up for safety and efficacy.
This data confirms results from multiple clinical studies that the Carillon therapy has an excellent safety profile, sustained clinical and mechanistic efficacy benefits, and is associated with improved long-term term survival.
ESC Heart Failure
doi: 10.1002/ehf2.12955
October 2020
- 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).
Department of Cardiology, Frankfurt University Hospital, Frankfurt, Germany
doi: 10.5114/amsad.2020.97160
June 2020
- 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.
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.
Cardiovascular Revascularization Medicine
Lipiecki et al.
February 2020
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.
Remodelling and Improved Hemodynamics Publications
Journal of Clinical Medicine
Piotr Kałmucki et al
August 2026
In FMR patients undergoing the Carillon procedure, higher baseline LV volumes may predict more pronounced reverse remodeling, defined as a decrease in LV volumes. Higher values of vena contracta may predict larger reductions in the mitral annular area. High baseline LV diameters could suggest improvements in LV volumes in disproportionate FMR and in LV diameters in proportionate FMR, probably due to different LV geometries.
ESC Heart Failure
Holder Priebe-Brämer et al
November 2025
This was a single-centre retrospective study of 204 consecutive patients (age 83 ± 6 years, 68% female, 72% HFrEF) with NYHA class II-IV HF and moderate and moderate-to-severe (grade 2 + or 3+) SMR planned for CMCS implantation between 2021 and 2024.
At 3 months:
- NYHA class improved by ≥1 category in 94% of patients and 98% achieved NYHA class I or II.
- MR decreased by ≥1 grade in 91% of patients, with all patients classified as grade 1+ or 2+ post-procedure.
- Vena contracta width decreased (6.43 ± 0.84 to 3.85 ± 1.19 mm; P < 0.001), and there was a reduction of LA area from 44.4 ± 6.0 to 35.4 ± 5.1 cm2 (P < 0.001).
- Diastolic filling was improved (change in E/E′ ratio from 20.1 ± 5.5 to 14.0 ± 3.8; P < 0.001), systolic pulmonary artery pressure was lower in follow-up (44 ± 11 to 35 ± 9 mm; P < 0.001), and there was also a clinically relevant reduction in median BNP levels from 2849 to 1390 pg/mL (P < 0.001).
- These changes were not different between HFrEF and HFpEF.
Polish Heart Journal
Kałmucki P, Lipiecki J, Siminiak T, et al.
April 2025
A new publication in the Polish Heart Journal confirms the clinical benefits of the Carillon Mitral Contour System in treating functional mitral regurgitation (FMR), with results drawn from three prospective studies: TITAN, TITAN II, and REDUCE-FMR. The combined analysis included 113 patients with symptomatic heart failure (NYHA class II–IV) and moderate-to-severe FMR. All patients were treated with the Carillon device, a percutaneous annuloplasty system designed to reduce mitral regurgitation via the coronary sinus.
Key 1-Year Outcomes:
- Mitral Regurgitation Reduction:
- Regurgitant Volume (RV) ↓ 10.5 mL
- Effective Regurgitant Orifice Area (EROA) ↓ 0.06 cm²
- Vena Contracta Width ↓ 0.16 mm
- Reverse Remodeling Indicators:
- LV End-Diastolic Volume (LVEDV) ↓ 15.2 mL
- LV End-Systolic Volume (LVESV) ↓ 13.7 mL
- Ejection Fraction (LVEF) ↑ 1.8%
- Mitral Annular Area ↓ 1.0 cm²
- Functional Improvement:
- NYHA class improved by ≥1 in 68% of patients
- 6-minute walk distance ↑ 51 meters
- KCCQ Quality of Life score ↑ 11.6 points
THT 2025 Symposium Presentation
Priebe-Brämer
2025
Real-world study of patients treated with the Carillon Mitral Contour System® as standard of care in a single center: Marien Hospital Witten, Germany
- 204 consecutive cases – 99% of attempted patients treated
- 201 patients evaluated – baseline vs 3 months
- Retrospective, non-randomized analysis of cases
- Largest single center published cohort of Carillon® patients worldwide
Conclusions:
- No intervention-related deaths
- A high success rate
- An excellent safety profile
- A rapid learning curve
- Large improvements in mechanistic variables
- High clinical benefits
- Ability to combine with alterative therapies
- Preservation of all possible future therapy options (including TEER and CRT)
American Heart Journal
Kalmucki et al.
November 2023
A comparison of clinical and echocardiographic outcomes of patients with HFrEF and proportionate and disproportionate FMR treated with indirect annuloplasty using the Carillon device. Pooled analysis of patients from 3 prospective studies that enrolled heart failure patients with persistent grade 2+ to 4+ FMR with >5.5 cm left ventricular (LV) end-diastolic diameter (LVEDD) and reduced ejection fraction.
- At 12 months, both groups showed improvements in all MR variables including regurgitant volume, EROA, and vena contracta.
- In patients with proportionate MR there were clinically relevant and statistically significant improvements in LV volumes and diameters.
- There was no independent relationship between the degree of proportionality as a continuous variable and the remodeling response to the Carillon therapy (change in LVEDV r=0.17; change in LVESV r=0.14).
- Percutaneous mitral annuloplasty with the Carillon device reduces MR in patients with both proportionate and disproportionate FMR, and also results in LV reverse remodeling in those with proportionate FMR.
TCT 2022 Poster
Goldberg S et al.
2022
Prospective trials of the Carillon Mitral Contour System have shown effective hemodynamic and clinical improvement in patients with heart failure and functional mitral regurgitation (FMR) including beneficial left ventricular and left atrial remodeling.
The CINCH registry is a multi-center, real-world study of patients treated with the Carillon device as standard of care. It is intended to enroll up to 250 patients in up to 40 centers in Germany.
The poster presented shows an interim analysis of 101 patients with up to 5 years follow-up data, including mortality, device related safety, change in NYHA class and rate of heart failure hospitalizations.
EJHF
Witte K et al.
2021
Although any degree of secondary mitral regurgitation (SMR) is known to further complicate heart failure symptoms and mortality, a treatment paradigm for patients with mild and moderate SMR is lacking. The recent publication on Carillon in the European Journal of Heart Failure – Treating symptoms and reversing remodelling: clinical and echocardiographic 1-year outcomes with percutaneous mitral annuloplasty for mild to moderate secondary mitral regurgitation – was particularly enlightening.
The purpose of the authors’ investigation was to determine the effects of percutaneous mitral annuloplasty on symptoms, 6-minute walk distance, and left ventricular (LV) structure and function in patients with mild or moderate SMR in heart failure with reduced ejection fraction. They examined a total of 68 patients from all Carillon trials who had mild and moderate SMR in a retrospective study of one-year outcomes. The findings were very encouraging:
- Mean 6-minute walk test distance increased by 34 m (95% CI 12 to 57; P < 0.01)
- Mean KCCQ scores increased from baseline by 10 units [95% confidence interval (CI) 3 to 17; P < 0.01]
- SMR grade improved in 25% of patients and was maintained in 58% of patients with changes in mean regurgitant volume of −7 mL (95% CI −11 to −3; P < 0.001), vena contracta −0.11 cm (95% CI −0.20 to −0.02; P < 0.05), and effective regurgitant orifice area −0.03 cm2 (95% CI −0.06 to −0.01; P < 0.05)
- New York Heart Association class status was maintained (48%) or improved (46%) in the vast majority of patients
- Survival over one year was 89% and freedom from HF hospitalization was 73%
The authors conclude: “Among patients with symptomatic HF and mild or moderate SMR on guideline-directed medical therapy, percutaneous mitral annuloplasty [i.e., the Carillon therapy] was associated with improvements in symptoms, SMR, a stabilization of LV structure and function, and high survival rates.”
JACC: Heart Failure
Anker et al.
May 2021
Although COAPT was successful, MITRA.fr was not. The prevailing theories as to the difference in the trials is the amount of left ventricular dysfunction in enrolled patients. This is a pooled analysis of patients with functional MR and severe LV enlargement (LV end-diastolic diameter > 65 mm) who were treated with GDMT and the Carillon device vs GDMT alone – i.e., MITRA.fr patients. Key outcomes of this analysis were changes over 1 year of follow-up in mitral valve and LV echocardiographic parameters, functional outcome, quality of life, mortality, and heart failure hospitalization (HFH).
- A total of 95 patients (67 Carillon group; 28 GDMT group) with severe LV enlargement were included.
- In the Carillon group, all mitral valve and LV morphology parameters were significantly improved at 1 year.
- Regurgitant volume decreased by 12 ml (p<0.001)
- MR grade decreased by 0.6 units (p<0.001)
- LV end-diastolic volume decreased by 25 cc (p=0.005)
- LV end-systolic volume decreased by 21 cc (p=0.01)
- Significant functional improvement differences were also noted between the Carillon group vs. GDMT group:
- Improvement of KCCQ score (15±4 vs 6±6; p=0.03)
- Incidence of HFH was 29.9% vs. 50.0% and the cumulative rate of HFH was 0.43 vs. 0.75 (p<0.001)
In conclusion, “In patients with functional MR and severe LV enlargement, the Carillon device improved mitral valve function, LV morphology, and functional outcome compared to patients receiving GDMT only. Preoperative LV dimension should not be a limiting factor when evaluating patient eligibility or anticipated response to therapy with the Carillon device.”
CATH’LAB
Lipiecki et al.
March 2021
Indirect Annuloplasty of the Mitral Valve The Carillon Mitral Contour System*
This article addresses the millions of heart failure patients worldwide that have a significantly increased risk of mortality because of functional mitral regurgitation (FMR). The article goes on to discuss the extensive clinical experience available for the Carillon device in treating FMR, advantages of the Carillon approach over alternative therapies, and highlights numerous patient groups that could benefit from treatment with the Carillon device. The authors conclude:
- The results of studies conducted to date suggest that FMR treatment with the Carillon device is both safe and effective in reducing both mitral regurgitation and left ventricular dysfunction.
- The short procedure time and the easy deployment of the device are certainly an advantage over other techniques available on the market.
- The prospective CARILLON US trial, currently underway, evaluates the effectiveness of the Carillon device on morbidity and mortality, and should validate the Carillon Mitral Contour System as a first-line interventional therapy.
*Original article published in the March 2021 edition of CATH’LAB. The article summary above has been translated from the original French publication with the assistance of machine translation (DeepL).
ESC Heart Failure
Khan et al.
March 2021
An individual patient data meta‐analysis was conducted from 3 prospective studies that enrolled heart failure patients with reduced ejection fraction and functional mitral regurgitation (FMR) implanted with the Carillon Mitral Contour System. The main outcomes assessed were changes from baseline in Kansas City Cardiomyopathy Questionnaire Overall Summary Scores (KCCQ-OSS), six-minute walk test (6MWT) distance and New York Heart Association (NYHA) classification at month 1 and 12 post device implantation.
- Among 139 patients included in the analysis, Carillon device significantly improved the 6MWT distance (63.0m; 95%CI 18.8-107.2, p=0.0056) and KCCQ-OSS score (15.1; 95%CI 5.6-24.7, p=0.0022) at 1 month from baseline. These benefits were sustained at 12 months (64.1m; 95%CI 13.2-115.0, p=0.0141for 6MWT distance, and 12.3; 95%CI 4.7-19.8, p=0.0019 for KCCQ-OSS score).
- More than 50% of the patients had improvements in KCCQ-OSS by ≥ 5 (60.4%; 95%CI 47.4-72.1) and 10 points (50.5%; 95%CI 34.9-66.0) at 12 months.
- Almost half of the patients experienced a ≥1 class improvement in NYHA class after implantation of the device at 1 month (67.9%; 95%CI 37.3-88.3) and at 12 months (48.8%; 95%CI 31.8-66.2).
- Results remained similar for KCCQ-OSS, 6MWT distance and NYHA classification when only patients with grade 3 or 4 mitral regurgitation were analyzed.
The Carillon Mitral Contour System significantly improved patient reported quality of life outcomes in heart failure patients with functional mitral regurgitation. Quality of life improvement in patients who were treated with the Carillon device was similar or better than other recently reported heart failure trials.
ESC Heart Failure
Khan et al.
February 2021
Patients with heart failure often have impaired physical function and reduced quality of life (QoL). Therefore, improving QoL by a minimum clinically important difference (MCID) is an important measure of the effectiveness of heart failure management.
This recently published paper is a rigorous analysis of the REDUCE FMR trial, focusing on the intended patient population based on core-lab adjudication*. It shows convincing 12-month results for the only sham-controlled randomized blinded study ever conducted in heart valve treatment.
- A substantially higher number of patients achieved MCID for all patient‐centered outcomes with the Carillon device compared with the sham procedure.
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- Improvement for the 6 minute walk test (6MWT)
- Improvement in NYHA class
- Improvement in QoL, based on the KCCQ survey
- Decrease in heart failure hospitalization
- In particular, the proportion of patients who achieved MCID improvement in the 6MWT (≥30 m increase) at 1 year of follow‐up from baseline was significantly higher in the Carillon device group compared with the sham group (59% vs. 23%, respectively; P = 0.029), even though REDUCE-FMR was only powered to detect the mechanistic endpoint of mitral regurgitation reduction.
- The number needed to treat (NNT) for a ≥30 m increase in 6MWT distance with the Carillon device was 2.8, and the NNT for a ≥20 m increase in 6MWT distance was 3.6.
- Additionally, all other clinical improvements of patients receiving the device relative to control are also encouraging and support the continued utilization of the Carillon device.
The authors conclude: “The patient population in this subgroup of those enrolled in REDUCE‐FMR (EROA, 0.31 cm2; LVDD, 66 mm) resembles that of the MITRA‐FR trial and is more generalizable to patients with HF and moderate to severe FMR. However, unlike the MITRA‐FR trial, our results show a trend towards improvement in patient‐centred outcomes with the Carillion device. In fact, the low NNT for all patient‐centred outcomes suggests that the Carillon device is likely to provide benefit in a large proportion of patients with FMR, rather than just a small subset. Furthermore, unlike the COAPT and MITRA‐FR trials, the REDUCE‐FMR trial used a sham procedure in the control group, which increases the reliability of its results by minimizing placebo and nocebo effects.”
*The intended patient population analysis was conducted to assess functional outcomes of patients with heart failure with reduced ejection fraction and moderate to severe (Grades 2+ to 4+) functional mitral regurgitation (FMR) treated with the Carillon device or control. Since 29.7% of patients were enrolled with only mild core-lab adjudicated MR grade 1+, this analysis focused on the intended patient population of the REDUCE FMR Trial with inclusion criteria of MR grades 2+ to 4+.
JACC: Cardiovascular Interventions
Rottländer et al.
December 2020
Echographic outcomes of patients with atrial derived FMR (aFMR) and heart failure with preserved ejection fraction (HFpEF) were compared to patients with ventricular derived FMR (vFMR) and heart failure with reduced ejection fraction (HFrEF) after percutaneous mitral valve repair with the Carillon Mitral Contour System.
- Patients with aFMR showed similar reductions in mitral annulus diameter and concomitant reduction in regurgitant volume through 3 months compared to those with vFMR.
- Significant reduction in MR as assessed by vena contracta, effective regurgitant volume as well as MR was seen as soon as 3 months after procedure in both groups.
- Similarly, after 3 months the proportion of patients with NYHA class III or IV was reduced from 92.8% to 42.8% which was maintained throughout 12 month follow-up.
The Carillon device is feasible in HFpEF patients with aFMR and is associated with significant reductions in MR.
ESC Heart Failure
Giallauria et al.
December 2020
An individual patient data meta‐analysis was conducted from 3 prospective studies that enrolled 209 heart failure patients with reduced ejection fraction and functional mitral regurgitation (FMR). Patients implanted with the Carillon Mitral Contour System or control were assessed for 12-month outcomes relating to mitral regurgitation severity, left ventricular (LV) remodeling, functional status, and heart failure‐related hospitalization.
- Patients implanted with the device showed significantly improved hemodynamics, MR severity (regurgitant volume and MR grade), left ventricular volume (LVEDV) and left atrial volume (LAV), as compared to those patients who did not receive a device at 12 months.
- Improvement of symptoms as assessed by change in NYHA class also significantly favored device implantation vs control (p<0.00001) with 69.9% (51/73) of implanted patients with baseline class III or IV improving by at least one class at 12 months.
- Similarly, the rate of hospitalizations due to heart failure (HFH) was significantly reduced in implanted patients (45.3% vs 64%, p=0.04).
- Sensitivity analysis performed on subjects with more severe MR (MR grade 3+/4+) at baseline supported the overall cohort in terms of hemodynamic improvement and maintained a significant improvement in HFH (43.9% vs 82.9%, p=0.04).
In conclusion, this comprehensive meta‐analysis of individual patient data has shown that the CARILLON device provides statistically significant and clinically meaningful benefits in LV volumes, NYHA functional class and indexes of mitral valve performance, along with a reduction in the rate of subsequent HFH.
ESC Heart Failure
Mitja Lainscak and Michael Böhm
December 2020
In this editorial Dr. Lainscak and Professor Böhm discuss the optimal management strategy for patients with Functional Mitral Regurgitation. There is a need in the therapeutic spectrum for additional therapies that are safe and can be deployed as an early intervention to reduce the need for repeated hospitalizations. The data presented by Gialluria et al. supports the use of the Carillon Mitral Contour System to achieve this goal. Owing to less invasive approaches, favourable effects on left ventricular volumes, and possibility of step‐wise upgrade with other interventions, Carillon could be considered early in the patient trajectory for a timely and effective management of heart failure patients with reduced ejection fraction and functional mitral regurgitation.
ESC Heart Failure
doi: 10.1002/ehf2.12719
May 2020
- 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.
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- 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.
ESC Heart Failure
doi: 10.1002/ehf2.12710
April 2020
- 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.
JACC: Heart Failure
doi: 10.1016/j.jchf.2019.06.011
November 2019
The REDUCE FMR study was the first double-blinded trial of a percutaneous heart valve therapy, achieved its primary endpoint, and demonstrated favorable reverse LV remodeling. A median 22% reduction in regurgitant volume was demonstrated, as assessed by a blinded, independent echo core lab. The results of The REDUCE FMR study are consistent with the prior Carillon device studies.
REDUCE FMR was the first ever double-blinded, randomized, parallel, sham-controlled RCT of a percutaneous heart valve therapy. The objective was to assess the safety and effectiveness of the Carillon Mitral Contour System for treatment of secondary (functional) mitral regurgitation (FMR) associated with heart failure. Key eligibility criteria were similar to the prior trials of the Carillon system including NYHA class II-IV, MR grade 2+ to 4+, LVEDD >55mm and an ejection fraction <50%, despite the use of stable guideline-directed medical therapy. The primary endpoint was change in regurgitant volume (RV) at 1 year by intention-to-treat analysis. Being double-blind, the study was of the highest scientific rigor – patients and assessors were blinded throughout follow-up and the independent echo core lab not only was blinded to treatment and the timing of the images but also read the images in random order.
In total, 120 patients were randomly allocated to treatment (87) or the sham-control (33) arm at 31 sites in Europe, Australia and New Zealand.
Echocardiographic evaluation was performed at the site prior to enrollment, and 35 patients (29.2%) were later judged by the echo core laboratory to have had MR 1+ at baseline. In 14 (16%) of those allocated to treatment, no device was implanted, due most commonly to coronary impingement (n=8) which resolved following device removal in all cases. The average device implant time was 64.2±34.8 minutes and total procedure time averaged 102.7±54.9 minutes. Freedom from device-related major adverse events (MAE) was 98.9%, with no device embolizations, device fractures, cardiac perforations or intra-procedural ischemic events. There were two deaths within 30 days, both in implanted patients attributed to progressive cardio-renal deterioration. The incidence of MAE at 1 year was not statistically different between the treatment and control groups (16.1% in treatment group vs. 18.2% in control group).
The primary endpoint was met with a statistically significant reduction in mitral RV in the treatment group as compared to the control group (decrease of 7.1 mL/beat vs. an increase of 3.3 mL/beat, p=0.049). A secondary analysis of patients with more severe FMR (MR grade ≥3+) demonstrated a similar pattern of changes. Patients in the treatment group (n=15) experienced a reduction in mitral RV of 12.8 mL/beat whereas patients in the control group (n=8) experienced an increase of 0.6 mL/beat (p=0.14). In addition to improvements in RV, favorable reverse LV remodeling was demonstrated, with a significant reduction in LV volumes in patients receiving the device vs. the control group.
Patients in the treatment group also experienced a significant improvement in 6-minute walk distance at 12 months compared with their baseline (p=0.002), whereas patients allocated to the control group did not (p=0.29). Likewise, the treatment group had a significant improvement in NYHA class at 12 months compared with baseline (p=0.002) whereas patients allocated to the control group did not (p=0.75).
With REDUCE FMR, the Carillon system became the first TMVr therapy to demonstrate significant favorable reverse LV remodeling at 1 year and significant reduction in RV in a blinded, randomized, sham-controlled trial.
J. Invasive Cardiology
doi: 10.1111/joic.12349
November 2016
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.
Open Heart
doi: 10.1136/openhrt-2016-000411
June 2016
The TITAN II study achieved its endpoint and showed significant improvements in echo parameters and patient function.
TITAN II was a single-arm study designed to assess the safety and efficacy of an updated version of the Carillon system. Inclusion and exclusion criteria were similar to those in TITAN. Patients had symptomatic congestive heart failure (NYHA class ≥2), MR grade 2+ to 4+, a dilated LV (LVEDD >55 mm) and an ejection fraction <40%. Quantitative assessments of MR were performed by an independent core echo laboratory, and MAE were reviewed by an independent data and safety monitoring board. In total, 36 patients were enrolled; 30 received a permanent implant.
J. Invasive Cardiology
February 2016
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.
Catheterization and Cardiovascular Interventions
doi: 10.1002/ccd.25689
September 2014
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.
European Journal of Heart Failure
doi:10.1093/eurjhf/hfs076
May 2012
The TITAN study met its endpoint and showed the Carillon device can significantly and safely reduce FMR severity in heart failure patients, resulting in significant favorable reverse LV remodeling over 12 months and improved measures of clinical outcomes over 24 months.
The TITAN study was a prospective, non-randomized multi-center European study. The objective of the study was to determine if the Carillon device could safely and effectively reduce FMR and yield a durable long-term clinical benefit. Follow-up included typical clinical and echo assessments through 1 year and implanted patients had an additional clinical follow-up assessment at 2 years. The study was rigorously conducted with oversight by independent parties including an echo core lab, clinical events committee, and a data and safety monitoring board. Key inclusion criteria included MR grade 2+ to 4+, NYHA Class II-IV and LVEF <40%.
Of the 53 patients enrolled in the study, 36 underwent permanent implant of the device. In 17 patients, the device was recaptured (due to transient coronary impingement (n=8) or <1 grade FMR reduction (n=9). These non-implant patients were followed as a comparator group.
Kardiol Pol 2011; 69, 3: 228-233
PMID: 21432789
2011
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.
Kardiol Pol. 2010.
PMID: 20131189
January 2010
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).
Circulation
doi: 10.1161/CIRCULATIONAHA.109.849885
July 2009
The first-in-human AMADEUS study met its endpoint and demonstrated successful deployment of the Carillon device and a significant reduction in FMR.
AMADEUS was a single-arm, first-in-human study designed to evaluate the safety and feasibility of the Carillon system. The study utilized several independent bodies to minimize bias and increase rigor, including a blinded echo core lab, clinical events committee, and data and safety monitoring board. Key inclusion criteria included moderate to severe FMR, NYHA class II-IV, LVEDD >55mm, and ejection fraction <40% receiving sustained stable and optimal HF medication regimen. The study enrolled 48 patients with the device successfully implanted in 30 patients. At six months, the degree of FMR reduction among five different quantitative echo measures ranged from 22-32%.
Cost Effectiveness Publications
BMC Cardiovascular Disorders
doi: 10.1186/s12872-015-0039-8
May 2015
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.
CRT Compatibility Publications
doi: 10.12998/wjcc.v4.i5.127
December 2013
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.
Catheter Cardiovasc Interv.
doi: 10.1002/ccd.22097
September 2009
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.
