David G. Reuter

Percutaneous Mitral Annuloplasty for Functional Mitral Regurgitation: Results of the CARILLON Mitral Annuloplasty Device European Union Study

Background— Functional mitral regurgitation (FMR), a well-recognized component of left ventricular remodeling, is associated with increased morbidity and mortality in heart failure patients. Percutaneous mitral annuloplasty has the potential to serve as a therapeutic adjunct to standard medical care. Methods and Results— Patients with dilated cardiomyopathy, moderate to severe FMR, an ejection fraction <40%, and a 6-minute walk distance between 150 and 450 m were enrolled in the CARILLON Mitral Annuloplasty Device European Union Study (AMADEUS). Percutaneous mitral annuloplasty was achieved through the coronary sinus with the CARILLON Mitral Contour System. Echocardiographic FMR grade, exercise tolerance, New York Heart Association class, and quality of life were assessed at baseline and 1 and 6 months. Of the 48 patients enrolled in the trial, 30 received the CARILLON device. Eighteen patients did not receive a device because of access issues, insufficient acute FMR reduction, or coronary artery compromise. The major adverse event rate was 13% at 30 days. At 6 months, the degree of FMR reduction among 5 different quantitative echocardiographic measures ranged from 22% to 32%. Six-minute walk distance improved from 307±87 m at baseline to 403±137 m at 6 months (P<0.001). Quality of life, measured by the Kansas City Cardiomyopathy Questionnaire, improved from 47±16 points at baseline to 69±15 points at 6 months (P<0.001). Conclusions— Percutaneous reduction in FMR with a novel coronary sinus-based mitral annuloplasty device is feasible in patients with heart failure, is associated with a low rate of major adverse events, and is associated with improvement in quality of life and exercise tolerance.

Treatment of functional mitral regurgitation by percutaneous annuloplasty: results of the TITAN Trial

Functional mitral regurgitation (FMR) contributes to morbidity and mortality in heart failure (HF) patients. The aim of this study was to determine whether percutaneous mitral annuloplasty could safely and effectively reduce FMR and yield durable long‐term clinical benefit.

Percutaneous Mitral Annular Reduction Provides Continued Benefit in an Ovine Model of Dilated Cardiomyopathy

Background—Functional mitral valve regurgitation plays a key role in the symptomatic severity and progression of heart failure. In an ovine model of dilated cardiomyopathy, we examined the chronic functional consequences of mitral regurgitation reduction using a recently developed novel percutaneous mitral annular reduction (PMAR) device. Methods and Results—Fourteen adult sheep were paced right ventricularly at 180 to 190 bpm for 5 weeks, leading to the development of moderate mitral valve regurgitation. After echocardiographic, hemodynamic, and neurohormonal analysis, 9 animals underwent PMAR. All animals were subsequently paced for another 28 days, and a final echocardiographic and hemodynamic study was conducted. Animals that had undergone PMAR showed significantly increased negative and positive dP/dt, whereas pulmonary capillary wedge pressure and mitral valve regurgitation were significantly reduced compared with those at device implant despite continued pacing. In conjunction, significant improvements in plasma norepinephrine and brain natriuretic peptide were apparent. Conclusions—The application of PMAR in animals with pacing-induced dilated cardiomyopathy and functional mitral valve regurgitation resulted in continued improvements in hemodynamic and neurohormonal parameters.

Effectiveness and Safety of Percutaneous Coronary Sinus-Based Mitral Valve Repair in Patients With Dilated Cardiomyopathy (from the AMADEUS Trial)

This report presents the procedural results from the AMADEUS trial that support coronary sinus (CS)-based percutaneous mitral annuloplasty. Despite therapeutic advances, functional mitral regurgitation (MR) continues to be a significant clinical problem for patients with dilated cardiomyopathy. CS approaches to mitral valve repair have been viewed with skepticism because of the distance of the CS/great cardiac vein from the mitral valve annulus and the potential to compress a coronary artery. This report presents the procedural results from the AMADEUS trial that support CS-based percutaneous mitral annuloplasty. Patients who met the inclusion criteria were eligible to receive a mitral annuloplasty device. Transesophageal echocardiography was used to assess changes in MR, angiography was used to assess the coronary arteries, and multislice computed tomography was used to evaluate the anatomic relations between the coronary venous system and the mitral valve. Acute MR reduction (grade 3.0 +/- 0.6 to 2.0 +/- 0.8, p <0.0001) and permanent implantation were achieved in 30 of 43 patients in whom an attempt was made. Additional measurements in 20 patients with implants showed reductions in the vena contracta (0.69 +/- 0.29 to 0.46 +/- 0.26 cm, p <0.0001), effective regurgitant orifice area (0.33 +/- 0.17 to 0.19 +/- 0.08 cm(2), p <0.0001), regurgitant volume (40 +/- 20 to 24 +/- 11 ml, p = 0.0005), and jet area/left atrial area (45 +/- 13% to 32 +/- 12%, p <0.0001). The coronary arteries were crossed in 36 patients (84%). Arterial compromise contributed to a lack of implantation in 6 patients (14%). No difference was found in the CS/great cardiac vein position relative to the annulus between the patients who did and did not have a reduction in MR. In conclusion, percutaneous mitral annuloplasty reduces MR and permanent implantation can be achieved in most eligible patients.

Feasibility and short‐term efficacy of percutaneous mitral annular reduction for the therapy of functional mitral regurgitation in patients with heart failure

Background: While functional mitral regurgitation (MR) commonly accompanies heart failure and contributes to heart failure progression, mitral repair in the setting of HF is not routinely practiced because of the attendant significant morbidity and mortality. This limitation has fostered the development of percutaneous devices to reduce MR, and our group has recently reported the short‐ and long‐term effectiveness of a percutaneous mitral annuloplasty device placed in the coronary sinus (Percutaneous Mitral Annuloplasty Device (PMAD), Cardiac Dimensions®, Inc., Kirkland, WA) in reducing MR in experimental animal models of heart failure with associated MR. In this article, we report results of a “first‐in‐human” study of temporary placement of the PMAD device. The aim of this study was to demonstrate the feasibility and safety of temporary deployment of this device in patients with functional MR in association with heart failure. Methods: Five patients undergoing scheduled coronary angiography with heart failure and functional MR (mean age 52 ± 9 [SD] years) were recruited, and four had anatomy suitable for deployment of the device. Transthoracic echocardiography and coronary angiography were performed before and after temporary placement and tensioning of the PMAD via the right internal jugular vein. Results: Temporary deployment of the device resulted in a significant reduction in the septal‐lateral mitral annular dimension from 35.5 ± 4.7 to 32.2 ± 4.6 mm (P = 0.02), with evidence of a reduction in the MR color Doppler area from 98.3 ± 43.6 to 83.3 ± 35.1 mm2 (P = 0.09). There were no complications. Conclusions: This first‐in‐human study of a novel device for percutaneous treatment of functional MR has shown that temporary placement of this device in the coronary sinus/great cardiac vein of patients with heart failure and MR is feasible and safe. Evidence of temporary reduction in MR and a reduction in mitral annular area indicate promise for device effectiveness in chronic implantation.

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.

Management of Atrial Arrhythmias Secondary to Severe Congenital Heart Disease with the Atrioverter

An atrial defibrillator was implanted in a patient with congcnitally corrected transposition of the great arteries, associated cardiac abnormalities, and persistent atrial arrhythmias. During a 15‐month follow‐up, 14 of 20 spontaneous episodes of his arrhythmias were successfully treated with the device. Two of these episodes were converted to sinus rhythm during ambulatory use of the device. Successful use of the device required implantation of a third defibrillation lead in the persistent leftsided superior caval vein and rigid control of congestive heart failure. An atrial defibrillator may be a valid treatment option in patients with congenital heart disease crippled by atrial fibrillation