The CINCH-FMR postmarket registry: Real-world long-term outcomes with percutaneous mitral valve repair with the Carillon Mitral Contour System®.

BACKGROUND: The Carillon® Mitral Contour System® has been studied in 4 prospective controlled studies in the treatment of functional mitral regurgitation (FMR) where it has been found to reduce mitral regurgitation, reduce left ventricular and atrial volumes, and be associated with improvements in clinical parameters. AIMS: The CINCH post-market registry is designed to evaluate immediate, mid-term and long-term outcomes from a post-approval study of the Carillon® device evaluated in real-world practice. METHODS: The CINCH post-market registry is a single-arm study of percutaneous mitral annuloplasty with the Carillon device in patients with functional (secondary) mitral regurgitation and symptomatic congestive heart failure when utilized in real-world conditions. Patient selection, echocardiographic hemodynamic measurements, and patient follow-up requirements were performed per standard of care at each institution. RESULTS: A total of 101 patients treated with the Carillon device at 13 sites in Germany were enrolled in the CINCH registry. The mean age was 75 ± 9 years, 57 % were male, and patient presentation included primarily NYHA class III (69 %) with MR grade 3 (68 %). Over 5 years of follow-up, all-cause mortality was 40.1 %, the incidence of HFH was 53.9 %, and the composite outcome of HFH or death was 66.4 %. At each follow-up interval through 5 years, statistically significant reductions in NYHA class (p < 0.05) and MR grade (p < 0.01) were reported. CONCLUSIONS: In this "real world" registry of the Carillon Mitral Contour System, procedural safety and medium-term follow-up outcomes is similar to the outcomes seen in the prospective, controlled clinical trials, despite being used in populations of patients that extend outside of those studied in the trials. The use of this therapy in patients with atrial functional mitral regurgitation, and heart failure with preserved ejection fraction, was notable, since these types of patients were excluded from the prospective, controlled trials. This supports possible additional patient populations who might benefit from this type of mechanical therapy. The safety profile of this therapy in this registry and in the earlier trials may support a potential role in earlier forms of secondary mitral regurgitation.

Anatomy and Topography of Coronary Sinus and Mitral Valve Annulus in Functional Mitral Regurgitation.

Background: We aimed to investigate the anatomical relationship of the coronary sinus (CS) and the mitral valve annulus (MVA) in patients with or without functional mitral regurgitation (FMR) using a multislice CT (MSCT) software to determine (a) the distance and angle of both CS and MVA plane and (b) the mitral annulus geometry. Methods: A total of 215 patients with MSCT and CS to MVA topography evaluation were enrolled in this retrospective study. Results: This patient cohort included 145 patients without FMR (67.4%, FMR ≤ 1+) and 70 patients (32.6%) with clinically relevant FMR (FMR ≥ 2+). Distance and angulation of CS to MVA planes were highly variable. In all groups, no significant correlation was documented between the distance or angle of CS to MVA planes and left ventricular ejection fraction, left ventricular end-diastolic diameter, or left atrial volume. A significant increase in total CS length could be found in patients with FMR ≥ 2+ compared to the FMR ≤ 1+ group. MVA diameter, area, and perimeter were significantly increased in FMR ≥ 2+ compared to FMR ≤ 1+. In the FMR ≥ 2+ cohort 61% showed a distance of CS to MVA plane <7.8 mm and 58% revealed an angle of CS to MVA plane <14.2°. Conclusion: Distance and angulation of CS to MVA topography using an MSCT approach are similar between patients with or without FMR, while CS length, MVA area, MVA perimeter, anterior-posterior diameter, and intercommissural diameter are significantly increased in all FMR subgroups. However, ~60% of FMR ≥ 2+ patients showed favorable CS to MVA topography for indirect mitral annuloplasty.

Mitral valve edge-to-edge repair versus indirect mitral valve annuloplasty in atrial functional mitral regurgitation.

OBJECTIVES: We aimed to compare indirect mitral annuloplasty using the Carillon Mitral Contour System and edge-to-edge repair via MitraClip in atrial functional mitral regurgitation (aFMR). BACKGROUND: In patients with left ventricular dilation, both edge-to-edge repair and indirect mitral annuloplasty are effective in reducing mitral regurgitation, while no clinical trial has compared both interventional methods in aFMR. METHODS: In a retrospective single-center analysis, 41 patients with aFMR underwent either edge-to-edge mitral valve repair (MitraClip group, n = 20) or indirect annuloplasty (Carillon group, n = 21). RESULTS: Both treatment groups showed high procedural success (100%) and low complication rates. Both treatment groups showed a comparable reduction of New York Heart Association (NYHA) classification postimplantation, after 3- and 12-months follow-up. Quantitative reduction in echocardiographic FMR parameters was significantly pronounced in the MitraClip group (reduction in vena contracta MitraClip vs. Carillon: postimplantation -74.6 ± 25.8 vs. -29.1 ± 17.8%, 3-months follow-up -65.8 ± 31.2 vs. -33.9 ± 17.5%, 12-months follow-up -50.8 ± 27.9 vs. -23.9 ± 17.0%, p < 0.05). Qualitative mitral valve assessment showed improved FMR class postimplantation, at 3-and 12-months follow-up in both treatment groups. Edge-to-edge repair revealed better results with lower average FMR classification compared to indirect coronary sinus-based annuloplasty. After 12-months left atrial (LA) volume was significantly reduced in the Carillon group, while in the MitraClip group no LA remodeling was found (reduction in LA volume MitraClip vs. Carillon at 12 months: +9.6 ± 25.1% vs. -12.3 ± 12.7%, p < 0.05). CONCLUSIONS: Both indirect mitral valve annuloplasty and edge-to-edge repair are feasible and safe in patients with aFMR, while the reduction in FMR was pronounced in the edge-to-edge repair group.

Percutaneous Coronary Sinus-Based Mitral Valve Repair Differentially Modulates Coronary Sinus to Mitral Valve Annulus Geometry and Topography.

Objectives: Coronary sinus (CS) based mitral annuloplasty using the Carillon device is a therapeutic option for the treatment of functional mitral valve regurgitation (FMR). Background: Little is known about the change of CS and mitral valve annulus (MVA) planes following Carillon implantation and how they are modulated by the tension applied on the device. Methods: In a retrospective single-center analysis, 10 patients underwent Carillon device implantation and received CT-angiography (CTA) prior and post CS based percutaneous mitral valve repair. Patients were assigned to responders or non-responders according to the 3-month transthoracic echocardiographic follow-up. A prototype software was used to assess distance and angulation of both CS (pre) or Carillon-device (post) and mitral annulus planes. Results: Comparison of the distance and angulation of the CS plane or Carillon device plane and the MVA plane prior and post intervention showed significant reduction of distance and unchanged angulation in responders while angulation was increased and distance reduced in non-responders without statistical significance. Furthermore, in FMR responders MVA perimeter, anterior-posterior diameter, intercommisural diameter and MVA area were decreased following successful indirect mitral valve annuloplasty, while in FMR non-responders Carillon device implantation had no effect on MVA geometry. Conclusions: Insufficient reduction of FMR following indirect mitral valve annuloplasty is associated with device malposition in relation to the mitral valve annulus. Patient selection using CTA-derived distance and angulation of CS to MVA planes is one option to increase effectiveness of indirect mitral valve annuloplasty.

Procedural planning of CS-based indirect mitral annuloplasty using CT-angiography.

OBJECTIVES: Coronary sinus (CS) based mitral annuloplasty using the Carillon device could be limited by compromise of the left circumflex artery (Cx). BACKGROUND: Computed tomography (CT) might be a feasible tool for preprocedural planning of indirect mitral valve annuloplasty. METHODS: In a retrospective analysis, 25 patients underwent Carillon device implantation and received CT-angiography (CTA) analysis prior to CS based percutaneous mitral valve repair. We used a retrospective approach with preprocedural CTA and intraprocedural coronary sinus angiography (CSA) measurements to determine the CS to Cx distance at the occlusion or compression point or in the distal landing zone in absence of Cx compromise. RESULTS: According to left coronary artery angiography, we identified 7 patients with Cx occlusion, 7 with Cx compression and 11 without Cx compromise. No difference in minimal CS to Cx distance between the three groups could be obtained. Also, neither distal CS diameter nor distal Carillon anchor size were related to Cx impingement. However, ROC analysis identified a CS to Cx distance of <8.6 mm specifically in the distal device landing zone to predict Cx compromise. Furthermore, CTA was accurate in assessing device length in comparison to CSA, but failed predicting Carillon device anchor size. CONCLUSIONS: CTA derived CS to Cx distance in the device landing zone might be helpful to predict Cx occlusion during Carillon device implantation. Furthermore, CTA predicted CS length but not anchor size correctly. Therefore, CT-angiographic procedural planning might help improving the results of percutaneous CS-based mitral valve repair.

Diagnostic role of coronary CT angiography in paroxysmal or first diagnosed atrial fibrillation.

OBJECTIVES: The presence of coronary artery disease (CAD) in patients hospitalised with paroxysmal or first diagnosed atrial fibrillation (AF) has major implications for antithrombotic therapy and cardiovascular event rate. Coronary CT angiography (CCTA) is a feasible tool to identify patients with concealed CAD. We aimed to evaluate the diagnostic role of early CCTA in patients hospitalised with paroxysmal or first diagnosed AF. METHODS: In a 5-year single-centre retrospective analysis, 566 patients with paroxysmal or first diagnosed AF who underwent CCTA were enrolled to investigate the presence of CAD. RESULTS: In patients with paroxysmal or first diagnosed AF, CCTA revealed CAD (coronary artery stenosis ≥50%) in 39.2%. Cardiac catheterisation was performed in 31.6%, confirming CAD in 13.1% of all patients. In 8.0% percutaneous coronary intervention and in 0.5% coronary artery bypass grafting was performed. In patients with paroxysmal or first diagnosed AF: (1) angina pectoris per se does not predict CAD; (2) multivariable regression analysis revealed age, male sex and diabetes as risk factors for CAD in AF; (3) Framingham Risk Score for coronary heart disease and CHA2DS2-VASc-Score were relevant risk scores of CAD and (4) the classification of Coronary Artery Calcium score reference values according to the Multi-Ethnic Study of Atherosclerosis was a predictor of CAD. CONCLUSION: Patients with paroxysmal or first diagnosed AF are at risk for CAD, while CCTA is a feasible diagnostic tool for CAD. We recommend to integrate CT calcium scoring and CCTA into the diagnostic workup of patients with new-onset or paroxysmal AF.

CT-Angiography to predict outcome after indirect mitral annuloplasty in patients with functional mitral regurgitation.

OBJECTIVES: Coronary sinus (CS) based mitral annuloplasty using the Carillon device is effective in reducing functional mitral valve regurgitation (FMR). However, this positive effect might be dependent on the relation between CS and the mitral annulus. BACKGROUND: Computed tomography (CT) assessment prior to mitral valve interventions is an emerging technique to optimize patient selection. METHODS: In a retrospective analysis 30 patients underwent Carillon device implantation and received CT-angiography prior to CS based percutaneous mitral valve repair. Patients were assigned to responders or non-responders according to the 3-month transthoracic echocardiographic follow-up including quantitative mitral valve regurgitation assessment. A prototype software for CS reconstruction was used to assess distance and angle of both CS and mitral annulus planes. RESULTS: Comparison of the distance and angle of the CS plane and the mitral valve annulus plane showed a significant shorter distance and lower angle in the responder group implicating an impact on procedure success. Our results suggest a CS plane and MV annulus plane with a favorably distance of <7.8 mm and an optimal angle of <14.2° could be considered favorably for mitral annuloplasty using a Carillon device. CONCLUSIONS: Distance and angle of mitral annulus and CS planes determined by three-dimensional reconstructions of CT-angiography might predict a reduction in echocardiographic FMR using Carillon Mitral Contour System.

A multicenter randomized trial comparing the effectiveness and safety of a novel vascular closure device to manual compression in anticoagulated patients undergoing percutaneous transfemoral procedures: The CELT ACD trial.

OBJECTIVES: This study compared the performance of Celt ACD® , a novel stainless steel based vascular closure device versus manual compression (MC) for femoral arteriotomy site hemostasis in patients undergoing percutaneous coronary procedures. BACKGROUND: Optimal access site management after percutaneous transfemoral procedures remains controversial. METHODS: Patients enrolled in this multicenter, randomized open label trial underwent 6-F diagnostic or interventional procedures and were assigned 2:1 to Celt ACD® versus MC. All patients were on full anticoagulation. The primary efficacy end point was time to hemostasis (TTH) and the primary safety end points were 30-day incidence of major procedural and access site related complications. RESULTS: The trial allocated 207 patients to Celt ACD® (n = 148) versus MC (n = 59) at 5 investigational sites. Baseline characteristics of the two groups were similar. Median TTH was 0 (Interquartile range (IQR): 0, 0.33) in the Celt ACD® compared to 8 min (IQR: 0, 20; P < 0.0001) in the MC group. Procedural success was 99.3% in the Celt ACD® versus 98.1% in the MC group (P = NS). There was a single major adverse event due to device maldeployment and embolization with successful percutaneous retrieval. The 30-day major complication rate was 0.7% in the Celt ACD® and 0% in the MC group (P = NS). CONCLUSIONS: After 6-F percutaneous invasive procedures in fully anticoagulated patients, TTH was significantly reduced in patients assigned to Celt ACD® compared to patients managed with MC. The 30-day rates of vascular complications were similarly low in both groups. (CELT ACD Trial; NCT01600482) © 2017 Wiley Periodicals, Inc.

Coronary sinus-based percutaneous annuloplasty as treatment for functional mitral regurgitation: the TITAN II trial.

OBJECTIVE: Functional (or secondary) mitral regurgitation (FMR) is associated with greater morbidity and worse outcomes in patients with congestive heart failure (CHF) and cardiomyopathy. The Carillon® Mitral Contour System® is a coronary sinus-based percutaneous therapy to reduce FMR. We evaluated the safety and efficacy of a modified version of the Carillon device in the treatment of patients with cardiomyopathy and FMR. METHODS: 36 patients with CHF, depressed left ventricular function (ejection fraction <40%) and at least moderate FMR underwent the Carillon device implant. RESULTS: There was 1 major adverse event within 30 days-a death (not device related)-occurring 17 days after the implant. Reductions in FMR and improvements in functional class and 6 min walk tests were seen, similar to prior studies. Device fractures in the high strain region of the proximal anchor (seen in prior studies) were not seen in this study. CONCLUSIONS: The modified Carillon device was associated with improvements in clinical and echocardiographic parameters in treating patients with FMR, while successfully addressing the issue of anchor fracture. This version of the Carillon device will be used in a blinded randomised trial of symptomatic patients with FMR.

Safety and performance of the DRug-Eluting Absorbable Metal Scaffold (DREAMS) in patients with de novo coronary lesions: 3-year results of the prospective, multicentre, first-in-man BIOSOLVE-I trial.

AIMS: Bioresorbable scaffolds were designed to overcome the limitations of permanent stents. In the BIOSOLVE-I study we aimed to assess the long-term safety and performance of a drug-eluting absorbable metal scaffold (DREAMS) at three years. METHODS AND RESULTS: In this prospective, multicentre first-in-man study, 46 patients with 47 de novo lesions were enrolled. We report the final results at three-year follow-up. Mean age was 65.3±9.7 years, lesions were 2.73±0.48 mm in diameter and 10.99±4.59 mm long. Follow-up at three years was available for 44 patients (one patient died of a non-cardiac cause and one patient withdrew consent). Three target lesion failures (TLF) occurred (6.6%), consisting of two clinically driven target lesion revascularisations at scheduled six-month angiography (4.3%) and one myocardial infarction after drug-eluting balloon treatment in a non-target lesion but target vessel at 12-month angiography (2.2%). No cardiac death or scaffold thrombosis occurred. Seven patients had additional angiographic follow-up at 28±4 months: in-scaffold late lumen loss had improved from 0.51±0.46 mm (median 0.28 mm) at 12 months to 0.32±0.32 mm (median 0.20 mm). CONCLUSIONS: The BIOSOLVE-I study showed excellent long-term outcomes at three years with a low TLF rate and no cardiac death or scaffold thrombosis. No TLF event was observed beyond 377 days.

Serial observation of drug-eluting absorbable metal scaffold: multi-imaging modality assessment.

BACKGROUND: The drug-eluting absorbable metal scaffold has demonstrated feasibility, safety, and promising clinical and angiographic outcomes at 12 months in human coronary arteries. This study aimed to evaluate the degradation rate and long-term vascular responses to drug-eluting absorbable metal scaffold. METHODS AND RESULTS: BIOSOLVE-I was a multicenter, single-arm, first-in-man trial assessing the safety and performance of drug-eluting absorbable metal scaffold in 46 patients with coronary artery disease. Patients who underwent serial invasive imaging, such as quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography, at 6 and 12 months were included in this study. From postimplantation to follow-up, arterial curvature and angulation were significantly increased by the degradation process. The greatest increase was seen from postimplantation to 6 months. The systolic-diastolic changes of the curvature and angulation gradually improved throughout the follow-up period. At the site of implantation, vasoconstriction (-10% mean reduction) was observed during the acetylcholine test at 6 months. The average percent hyperechogenicity of the scaffolded segments showed a continuous decrease over time, with the most pronounced changes within the first 6 months (from 22.1±7.0% to 15.8±3.7%; P<0.001). Struts discernible on optical coherence tomography at 6 and 12 months showed full neointimal coverage, with stabilization of the mean scaffold area from 6 to 12 months. Furthermore, the mean neointimal area (1.55±0.51 versus 1.58±0.34 mm(2); P=0.794) remained unchanged from 6 to 12 months. CONCLUSIONS: This serial analysis of drug-eluting absorbable metal scaffold confirmed the safety and efficacy of this new device, with vasomotion restoration and continued degradation over time demonstrated by multi-invasive imaging modalities. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01168830.

Safety and performance of the drug-eluting absorbable metal scaffold (DREAMS) in patients with de-novo coronary lesions: 12 month results of the prospective, multicentre, first-in-man BIOSOLVE-I trial.

BACKGROUND: Bioabsorbable vascular scaffolds were developed to overcome limitations of permanent bare-metal or drug-eluting coronary stents­ie, stent thrombosis (despite prolonged dual antiplatelet therapy), the life-long presence of a caged vessel segment that does not allow vasomotion or remodelling, and chronic vessel wall inflammation. We assessed the safety and performance of a new magnesium-based paclitaxel-eluting absorbable metal scaffold in symptomatic patients with de-novo coronary lesions. METHODS: We did a prospective, multicentre, first-in-man trial (BIOSOLVE-1) of the drug-eluting absorbable metal scaffold (DREAMS). 46 patients with 47 lesions were enrolled at five European centres. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation, at 6 and 12 months. Clinical follow-up was scheduled at 1, 6, 12, 24, and 36 months. Patients were consecutively assigned to angiographic and intravascular ultrasonographic follow-up at 6 months or 12 months. Optical coherence tomography was done in some patients. All patients were recommended to take dual antiplatelet therapy for at least 12 months. This trial is registered with ClinicalTrials.gov, number NCT01168830. FINDINGS: Overall device and procedural success was 100%. Two of 46 (4%) patients had target lesion failure at 6 months (both clinically driven target lesion revascularisations), which rose to three of 43 (7%) at 12 months (one periprocedural target vessel myocardial infarction occurred during angiography at the 12 month follow-up visit). We noted no cardiac death or scaffold thrombosis. INTERPRETATION: Our results show feasibility, a good safety profile, and promising clinical and angiographic performance results up to 12 months for DREAMS. Our promising clinical results show that absorbable metal scaffolds might be an alternative to polymeric absorbable scaffolds. FUNDING: Biotronik.

Acute vasomotor paralysis and potential downstream effects of paclitaxel from stents implanted for saphenous vein aorto-coronary bypass stenosis.

Implantation of bare metal stents (BMS) induces the release not only of particulate debris, but also of soluble vasoconstrictors which contribute to microvascular impairment. So this study aimed at addressing the potential attenuation of such vasoconstriction using paclitaxel eluting stents (PES). Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stent [n = 14 BMS, n = 14 PES, n = 3 sirolimus eluting stents (SES)] implantation in patients with saphenous vein aorto-coronary bypass stenosis and analyzed for plasma serotonin and thromboxane B(2) concentrations. The vasoconstriction of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium in response to coronary arterial or aspirate plasma was quantified and normalized to that by potassium chloride (KCl(max) = 100%). Coronary arterial plasma before stent implantation induced a vasoconstriction of 30-43%, which was independent of endothelial integrity. Serotonin-release was 2.2 ± 0.5 µmol/l with BMS and 2.0 ± 0.4 µmol/l with PES, thromboxane B(2)-release was 26 ± 5 pg/ml with BMS and 22 ± 8 pg/ml with PES. BMS- and SES-aspirate plasma induced a vasoconstriction of 68 ± 18% (+E)/93 ± 14% (-E) and 81 ± 17% (+E)/124 ± 14% (-E), respectively. In contrast, PES-aspirate plasma induced only minor vasoconstriction of 8 ± 3% (+E)/12 ± 5% (-E). Addition of paclitaxel to BMS-aspirate plasma attenuated vasoconstriction. PES-aspirate induced microtubular condensation in immunofluorescence microscopy. Results indicate that aspirate from PES implantation attenuates vasoconstriction, possibly secondary to microtubular stabilization. Such acute downstream vascular paralysis could be beneficial in preventing a no-reflow phenomenon in patients undergoing stenting.