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.

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.

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.

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.

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.

Vasoconstrictor potential of coronary aspirate from patients undergoing stenting of saphenous vein aortocoronary bypass grafts and its pharmacological attenuation.

RATIONALE: Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion. OBJECTIVE: To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action. METHODS AND RESULTS: Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B(2), and tumor necrosis factor (TNF)α was measured. The response of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21±5% and the aspirate plasma after stenting induced 95±8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B(2), and TNFα release into aspirate plasma increased by 1.9±0.2 µmol/L, 25.6±3.1 pg/mL, and 19.7±6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNFα did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries +E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside (+E, 3.3×10(-8); -E, 1.9×10(-8) mol/L) and verapamil (+E, 8.3×10(-8); -E, 7.8×10(-8) mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker. CONCLUSION: Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNFα somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium.

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.

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.

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.

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.

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.

Percutaneous mitral annuloplasty device leaves free access to cardiac veins for resynchronization therapy.

OBJECTIVES: To assess the feasibility to place a left ventricular lead into the coronary sinus following percutaneous mitral annuloplasty. BACKGROUND: Percutaneous coronary sinus-based mitral annuloplasty may reduce functional mitral regurgitation in chronic systolic heart failure. However, concerns have been raised whether the placement of an annular remodeling device in the coronary sinus might preclude subsequent lead placement for resynchronization therapy (CRT). METHODS: Three patients with ischemic cardiomyopathy included in the AMADEUS trial underwent CRT 7 to 8 months after implantation of a mitral valve annuloplasty device. RESULTS: Fluoroscopy and control coronary angiography revealed a stable position of the annuloplasty device without any compromise of coronary blood flow. Intravascular ultrasound of the coronary sinus excluded any thrombus formation and demonstrated smooth endothelialization of the annular remodeling device. Access of 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. CONCLUSIONS: Positioning a left ventricular pacing lead for CRT is feasible after permanent implantation of a coronary sinus-based mitral annuloplasty device in patients with dilated cardiomyopathy.

[Percutaneous mitral valve annuloplasty with the carillon mitral contour system by cardiac dimensions. A minimally invasive therapeutic option for the treatment of severe functional mitral valve regurgitation]. / Perkutane Mitralklappenanulorrhaphie mit dem Carillon XE2 Mitral Contour System von Cardiac Dimensions. Ein minimalinvasiver Therapieansatz zur Behandlung der funktionellen Mitralklappeninsuffizienz.

Morbidity in patients with systolic heart failure is significantly increased by functional mitral valve regurgitation. In addition to pharmaceutical treatment or surgical reconstruction of the impaired valve, minimally invasive procedures have continuously advanced into the focus of interest. The Carillon Mitral Contour System (Cardiac Dimensions) is a new catheter-based method to converge dehiscent mitral valve leaflets with implantation of a nitinol clip into the coronary sinus, leading to a closer approach of the valve leaflets with subsequent decrease in mitral regurgitation. The device is implanted via a central venous catheter, using a special delivery system under fluoroscopy. The immediate success of minimizing mitral valve regurgitation is verified by online transesophageal echocardiography (TEE), device-related impairment of perfusion of contiguous coronary vessels is ruled out by coronary angiography performed simultaneously during deployment of the device. As soon as reduction of the mitral valve regurgitation is demonstrated in TEE, the Carillon System is disconnected from the delivery system, before, however, the Carillon device can be withdrawn into the delivery system as necessary. Following the successful implantation of the Carillon Mitral Contour System, a left ventricular lead for cardiac resynchronization therapy can still be successfully placed alongside through the coronary sinus.

Familial hypertrophic cardiomyopathy-linked mutant troponin T causes stress-induced ventricular tachycardia and Ca2+-dependent action potential remodeling.

The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy or fibrosis. Enhanced cardiac function has been associated with myofilament Ca2+ sensitization, suggesting altered cellular Ca2+ handling. In the present study, we compare cellular Ca2+ transients and electrophysiological parameters of 64 I79N-Tg and 106 control mice in isolated myocytes, isolated perfused hearts, and whole animals. Ventricular action potentials (APs) measured in isolated I79N-Tg hearts and myocytes were significantly shortened only at 70% repolarization. No significant differences were found either in L-type Ca2+ or transient outward K+ currents, but inward rectifier K+ current (IK1) was significantly decreased. More critically, Ca2+ transients of field-stimulated ventricular I79N-Tg myocytes were reduced and had slow decay kinetics, consistent with increased Ca2+ sensitivity of I79N mutant fibers. AP differences were abolished when myocytes were dialyzed with Ca2+ buffers or after the Na+-Ca2+ exchanger was blocked by Li+. At higher pacing rates or in presence of isoproterenol, diastolic Ca2+ became significantly elevated in I79N-Tg compared with control myocytes. Ventricular ectopy could be induced by isoproterenol-challenge in isolated I79N-Tg hearts and anesthetized I79N-Tg mice. Freely moving I79N-Tg mice had a higher incidence of nonsustained ventricular tachycardia (VT) during mental stress (warm air jets). We conclude that the TnT-I79N mutation causes stress-induced VT even in absence of hypertrophy and/or fibrosis, arising possibly from the combination of AP remodeling related to altered Ca2+ transients and suppression of IK1.

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.

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.