MitraClip Implantation for the Treatment of New-Onset Systolic Anterior Motion of the Mitral Valve After Transcatheter Aortic Valve Replacement.

New-onset systolic anterior motion of the anterior mitral valve leaflet in patients undergoing transcatheter aortic valve replacement is a rare pathophysiologic mechanism leading to postprocedural development of mitral regurgitation and, eventually, left ventricular outflow obstruction. We report the first human case of successful MitraClip implantation to treat new-onset systolic anterior motion of the mitral valve after transcatheter aortic valve replacement causing severe obstruction to left ventricular outflow that was unresponsive to standard medical therapy.

Percutaneous mitral valve repair with the MitraClip system in the elderly: One-year outcomes from the GRASP registry.

BACKGROUND: Although mitral regurgitation (MR) affects a relevant and increasing number of elderly, an optimal management of this high-risk population is challenging. METHODS AND RESULTS: The aim of this prospective, observational study was to compare one-year outcomes of MitraClip therapy in high surgical risk patients with moderate-to-severe or severe MR between patients aged <75 versus ≥75years. A total of 180 patients were included: 92 were <75years and 88 were ≥75years old. At one-year follow-up the primary efficacy endpoint (composite of death, surgery for mitral valve dysfunction and grade 3+ or 4+ MR) occurred in 41 patients (24.5%), with similar rates between those aged <75years (23.9%) and those ≥75years (25.2%), p=0.912. A total of 21 (12.2%) deaths were observed within 1year after the MitraClip procedure, without significant differences in cumulative mortality rates between elderly and younger patients (10.8% vs. 13.3%, respectively, p=0.574). Compared with baseline, the significant reduction in MR severity achieved after the procedure was sustained at one-year follow-up, in both elderly and younger patients and a significant improvement in NYHA functional class was observed in both groups. A total of 18 (10.0%) patients experienced a re-hospitalization for acute heart failure within one-year after the MitraClip procedure, with no significant differences between elderly and younger. At one-year follow-up both elderly and younger patients showed significant reductions in left ventricular volumes, with changes of similar extent between the two subgroups. CONCLUSIONS: MitraClip therapy can be considered a viable option also among subsets with more advanced age.

Impact of chronic kidney disease on outcomes after percutaneous mitral valve repair with the MitraClip system: insights from the GRASP registry.

AIMS: Our aim was to evaluate the impact of baseline chronic kidney disease (CKD) on clinical outcomes after percutaneous edge-to-edge mitral valve repair (PMVR). METHODS AND RESULTS: Two hundred and fourteen consecutive patients dichotomised by the presence of baseline CKD (n=113) or no-CKD (n=101) had their clinical outcomes compared up to 12-month follow-up. The primary safety endpoint was the incidence of major adverse events and the primary efficacy endpoint was freedom from death, surgery for MV dysfunction, or grade ≥3+ MR. The primary safety endpoint was demonstrated in 12.4% vs. 2.0% in CKD and no-CKD patients, respectively (p=0.003). The primary efficacy endpoint at 12 months was significantly lower in CKD patients (65.8% vs. 84.2%, respectively, log-rank p=0.005). While MR reduction and NYHA functional class improvement were mostly sustained and equivalent up to 12 months in no-CKD patients, they were impaired in CKD patients. Baseline CKD was an independent predictor of the primary efficacy endpoint (adjusted HR 2.48, 95% CI: 1.29 to 4.79, p=0.006) and calcified leaflet predicted grade ≥3+ MR at 12 months (adjusted HR 6.56, 95% CI: 2.71 to 15.88, p<0.001). CONCLUSIONS: CKD patients had worse clinical outcomes compared with no-CKD patients post PMVR. CKD was an independent predictor of the primary efficacy endpoint, whereas calcified leaflet was an independent predictor of grade ≥3+ MR at 12 months.

Extended use of percutaneous edge-to-edge mitral valve repair beyond EVEREST (Endovascular Valve Edge-to-Edge Repair) criteria: 30-day and 12-month clinical and echocardiographic outcomes from the GRASP (Getting Reduction of Mitral Insufficiency by Percutaneous Clip Implantation) registry.

OBJECTIVES: This study sought to compare, in high-risk patients with 3+ to 4+ mitral regurgitation (MR) dichotomized by baseline echocardiographic features, acute, 30-day, and 12-month outcomes following percutaneous mitral valve repair using the MitraClip. BACKGROUND: The feasibility and mid-term outcomes after MitraClip implantation in patients with echocardiographic features different from the EVEREST (Endovascular Valve Edge-to-Edge Repair) I and II trials have been scarcely studied. METHODS: Clinical and echocardiographic outcomes through 12-month follow-up of consecutive patients who underwent MitraClip implantation were obtained from an ongoing prospective registry. Two different groups, divided according to baseline echocardiographic criteria (investigational group [EVERESTOFF] and control group [EVERESTON]), were compared. RESULTS: Seventy-eight patients were included in EVERESTOFF and 93 patients in EVERESTON groups. Important and comparable acute reductions in MR and no clip-related complications were revealed. The primary safety endpoint at 30 days was comparable between groups (2.6% vs. 6.5%, respectively, p = 0.204); in addition, MR reduction was mostly sustained, whereas equivalent improvement in New York Heart Association functional class were demonstrated. Kaplan-Meier freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR at 12 months was demonstrated in 71.4% and 76.2%, respectively, in the EVERESTOFF and EVERESTON groups (log rank p = 0.378). Significant improvements in ejection fraction and reduction in left ventricle volumes were demonstrated in both groups over time, but the baseline between-group differences were sustained. CONCLUSIONS: MitraClip implantation in patients with expanded baseline echocardiographic features, compared with the control group, was associated with similar rates of safety and efficacy through 12-month follow-up. Further validation of our findings is warranted.

Gender-related clinical and echocardiographic outcomes at 30-day and 12-month follow up after MitraClip implantation in the GRASP registry.

OBJECTIVES: To assess the influence of patients' gender on the outcomes of percutaneous edge-to-edge mitral valve repair (PMVR) using the MitraClip system. BACKGROUND: Although gender-related differences have been extensively documented in patients who undergo surgery for moderate-to-severe (3+) and severe (4+) mitral regurgitation (MR), studies assessing whether these differences exist after PMVR are lacking. METHODS: Clinical and echocardiographic data through 12-month follow up from 171 consecutive patients whom underwent MitraClip implantation and were dichotomized by the gender (106 males and 65 females) were obtained. The primary safety endpoint was the incidence of major adverse events at 30 days and the primary efficacy endpoint was freedom from death, surgery for mitral valve dysfunction, or grade≥3+ MR at 12-month follow up. RESULTS: The primary safety endpoint was observed in four males (3.8%) and four females (6.2%) (P=0.358). Remarkable reduction in MR postprocedure was revealed in both groups, and these results were mostly sustained. Furthermore, left ventricle reverse remodeling and New York Heart Association (NYHA) functional class improvement were revealed in both groups, but females tended to demonstrate worse results over time (P=0.083). The primary efficacy endpoint obtained by Kaplan-Meier estimates was observed in 76.3 and 70.2%, respectively (log rank P=0.231). CONCLUSIONS: MitraClip implantation in patients with 3+ and 4+ MR is safe and efficacious until mid-term follow up, regardless of patients' gender. Despite improvement in NYHA functional class in both groups, female gender demonstrated a trend toward poorer results. Further validation of our findings is warranted.

Association of tricuspid regurgitation with clinical and echocardiographic outcomes after percutaneous mitral valve repair with the MitraClip System: 30-day and 12-month follow-up from the GRASP Registry.

AIM: The aim of this study was to evaluate the association of baseline tricuspid regurgitation (TR) on the outcomes after percutaneous mitral valve repair (PMVR) with the MitraClip system. METHODS AND RESULTS: Data from 146 consecutive patients with functional mitral regurgitation (MR) were obtained. Two different groups, dichotomized according to the degree of pre-procedural TR (moderate/severe, n = 47 and none/mild, n = 99), had their clinical and echocardiographic outcomes through 12-month compared. At 30-day, the primary safety endpoint was significantly higher in moderate/severe TR compared with none/mild TR (10.6 vs. 2.0%, P = 0.035). Marked reduction in MR grades observed post-procedure were maintained through 12 months. Although NYHA functional class significantly improved in both groups compared with baseline, it was impaired in moderate/severe TR compared with the none/mild TR group (NYHA > II at 30 day: 33.3 vs. 9.2%, P < 0.001; at 1 year: 38.5 vs. 12.3%, respectively, P = 0.006). Left ventricle reverse remodelling and ejection fraction improvement were revealed in both groups. The primary efficacy endpoint at 12-month determined by freedom from death, surgery for mitral valve dysfunction, or grade ≥ 3+ MR was comparable between groups, but combined death and re-hospitalization for heart failure rates were higher in the moderate/severe TR group. Multivariable Cox regression analysis demonstrated that baseline moderate/severe TR and chronic kidney disease were independent predictors of this combined endpoint. CONCLUSIONS: Although PMVR with MitraClip led to improvement in MR, TR, and NYHA functional class in patients with baseline moderate/severe TR, the primary safety endpoint at 30-day was impaired, while moderate/severe TR independently predicted death and re-hospitalization for heart failure at 12-month.

One- and twelve-month safety and efficacy outcomes of patients undergoing edge-to-edge percutaneous mitral valve repair (from the GRASP Registry).

The aim of this study was to report on the 30-day and 1-year outcomes of percutaneous mitral valve repair with the MitraClip technique in patients with grade ≥3+ mitral regurgitation (MR) at high risk for conventional surgical therapy enrolled in the prospective Getting Reduction of Mitral Insufficiency by Percutaneous Clip Implantation (GRASP) registry. Acute device success was defined as residual MR ≤2+ after clip implantation. The primary safety end point was the rate of major adverse events at 30 days. The primary efficacy end point was freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR at 30 days and 1 year. A total of 117 patients were treated. Eighty-nine patients (76%) presented with functional MR and 28 patients (24%) with organic MR. Acute device success was observed in all patients. Device implantation time significantly diminished with experience and varied significantly between cases with 1 versus ≥2 clips. No procedural mortality was recorded. Major adverse events occurred in 4 patients at 30 days (4.3%). Deterioration to MR ≥3+ was recorded in 25% of patients with degenerative MR and 7% of those with functional MR at 1 year. No surgery for mitral valve dysfunction occurred within 1 year. Freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR was 96.4% and 75.8% at 30 days and 1 year, respectively. No significant differences were noted in the primary efficacy end point between patients with degenerative MR and those with functional MR. In conclusion, percutaneous mitral valve repair with the MitraClip technique was shown to be safe and reasonably effective in 117 patients from a real-world setting.

Neutral endopeptidase inhibition and the natriuretic peptide system: an evolving strategy in cardiovascular therapeutics.

Hypertension and heart failure (HF) are common diseases that, despite advances in medical therapy, continue to be associated with high morbidity and mortality. Therefore, innovative therapeutic strategies are needed. Inhibition of the neutral endopeptidase (NEPinh) had been investigated as a potential novel therapeutic approach because of its ability to increase the plasma concentrations of the natriuretic peptides (NPs). Indeed, the NPs have potent natriuretic and vasodilator properties, inhibit the activity of the renin-angiotensin-aldosterone system, lower sympathetic drive, and have antiproliferative and antihypertrophic effects. Such potentially beneficial effects can be theoretically achieved by the use of NEPinh. However, studies have shown that NEPinh alone does not result in clinically meaningful blood pressure-lowering actions. More recently, NEPinh has been used in combination with other cardiovascular agents, such as angiotensin-converting enzyme inhibitors, and antagonists of the angiotensin receptor. Another future possible combination would be the use of NEPinh with NPs or their newly developed chimeric peptides. This review summarizes the current knowledge of the use and effects of NEPinh alone or in combination with other therapeutic agents for the treatment of human cardiovascular disease such as HF and hypertension.

Left cardiac chambers reverse remodeling after percutaneous mitral valve repair with the MitraClip system.

BACKGROUND: Successful mitral valve surgical repair, decreasing volume overload, has been shown to provide reverse left ventricular (LV) and/or left atrial remodeling in most patients. Percutaneous mitral valve repair with the MitraClip system (Abbott, Abbott Park, IL) has been associated with favorable clinical outcomes in patients with mitral regurgitation at high risk of surgery. However, specific data on left cardiac chambers reverse remodeling after such procedures are limited. METHODS: This was a prospective observational study of consecutive patients at high risk of surgery, with moderate-to-severe or severe mitral regurgitation undergoing MitraClip system implantation. Follow-up echocardiography was performed at 6 months. The evaluated parameters were the LV end-diastolic and end-systolic volume indexes, LV sphericity index, LV ejection fraction, and left atrial volume index. Reverse LV remodeling was defined as a decrease of 10% in the LV end-diastolic volume index. RESULTS: The study population included 44 patients: 14 with degenerative and 30 with functional mitral regurgitation. At 6 months of follow-up, significant reductions in the median and interquartile range of the sphericity index (from 0.57 [interquartile range 0.54-0.62] to 0.54 [interquartile range 0.50-0.58]; P < .001), LV end-diastolic volume index (from 79.4 mL/m(2) [interquartile range 63.0-102.2] to 60.7 mL/m(2) [50.8-84.4]; P < .001), and LV end-systolic volume index (from 49.3 mL/m(2) [interquartile range 28.2-70.5] to 28.9 mL/m(2) [interquartile range 22.2-55.8]; P < .001) were observed. The LV ejection fraction improved significantly (from 38.0% [interquartile range 30.0-55.0%] to 46.0% [interquartile range 35.0-58.0%]; P < .001) from baseline to 6 months. Minor differences in the left atrial volume index were observed. Reverse remodeling, according to the specified definition, was observed in 77.3% of the patients. CONCLUSIONS: The present study reports positive LV reshape effects after mitral valve repair with the MitraClip system, showing significant improvements in LV size and function.

Percutaneous mitral valve repair in patients with prior cardiac surgery.

BACKGROUND AND AIM OF THE STUDY: The safety of percutaneous mitral valve repair with the MitraClip system has been documented. However, few data are available on high-risk patients not amenable to surgery. The aim of this study was to evaluate the outcomes of patients with prior cardiac surgery undergoing MitraClip therapy (Abbott, Abbott Park, Chicago, IL, USA) for severe mitral regurgitation. METHODS: We reported two cases of percutaneous treatment of severe mitral regurgitation performed in patients who had previously undergone cardiac surgery with the implantation of mechanical prosthetic aortic valve. RESULTS: In both the reported cases a sustained reduction in mitral regurgitation severity was obtained at two-year follow-up, with a relevant improvement in terms of clinical status and quality of life. CONCLUSIONS: Percutaneous mitral valve repair using the MitraClip system represents a viable treatment choice for severe mitral regurgitation in high-risk patients who have previously undergone cardiac surgery.

Percutaneous mitral valve repair with the MitraClip system: acute results from a real world setting.

AIMS: This study sought to evaluate the feasibility and early outcomes of a percutaneous edge-to-edge repair approach for mitral valve regurgitation with the MitraClip system (Evalve, Inc., Menlo Park, CA, USA). METHODS AND RESULTS PATIENTS: were selected for the procedure based on the consensus of a multidisciplinary team. The primary efficacy endpoint was acute device success defined as clip placement with reduction of mitral regurgitation to < or =2+. The primary acute safety endpoint was 30-day freedom from major adverse events, defined as the composite of death, myocardial infarction, non-elective cardiac surgery for adverse events, renal failure, transfusion of >2 units of blood, ventilation for >48 h, deep wound infection, septicaemia, and new onset of atrial fibrillation. Thirty-one patients (median age 71, male 81%) were treated between August 2008 and July 2009. Eighteen patients (58%) presented with functional disease and 13 patients (42%) presented with organic degenerative disease. A clip was successfully implanted in 19 patients (61%) and two clips in 12 patients (39%). The median device implantation time was 80 min. At 30 days, there was an intra-procedural cardiac tamponade and a non-cardiac death, resulting in a primary safety endpoint of 93.6% [95% confidence interval (CI) 77.2-98.9]. Acute device success was observed in 96.8% of patients (95% CI 81.5-99.8). Compared with baseline, left ventricular diameters, diastolic left ventricular volume, diastolic annular septal-lateral dimension, and mitral valve area significantly diminished at 30 days. CONCLUSION: Our initial results with the MitraClip device in a very small number of patients indicate that percutaneous edge-to-edge mitral valve repair is feasible and may be accomplished with favourable short-term safety and efficacy results.

Spontaneous coronary artery dissection: a report of two atypical cases.

Spontaneous coronary artery dissection is a rare pathology that has no exact incidence, etiology, pathogenesis and evolution in literature. We report two cases of two women with coronary artery dissection, uncommon clinical presentation of acute coronary syndrome and without identifiable risk factors. A review of the literature and the management of this condition are presented.

Percutaneous closure of left atrial appendage to prevent embolic events in high-risk patients with chronic atrial fibrillation.

BACKGROUND: Percutaneous closure of the left atrial appendage (LAA) is a novel alternative for the treatment of patients with atrial fibrillation (AF) and with a high risk of stroke who are not eligible for long-term anticoagulation therapy. The aim of this study was to asses the safety, feasibility, and long-term efficacy of this procedure. METHODS: From July 2004 to June 2007, 20 patients (13 male, mean age 69 +/- 8 years) with non-valvular AF (NV-AF) underwent LAA percutaneous closure using the PLAATO system, implanted through a transeptal access. All patients had contraindications to anticoagulant therapy and were at high risk for cardioembolic stroke (mean CHADS(2) score 3 +/- 1.2). A trans-thoracic echocardiogram was performed at 1, 3, and every 6 months after the procedure, whereas a trans-oesophageal echocardiogram (TOE) was scheduled at 6 months. After 24 months, a phone interview was obtained. RESULTS: All procedures were successfully performed in 18 patients. In two patients, LAA closure was not feasible for the presence of a multilobed LAA. Two patients underwent percutaneous closure of patent foramen ovale in the same session. In one patient, the procedure was complicated by cardiac perforation with pericardial effusion, treated with pericardiocentesis. At a mean follow up of 40 +/- 10 months, no embolic events occurred. One patient died, after 36 months, for gastric cancer. TOE examination showed the complete exclusion of the LAA in all patients. CONCLUSIONS: Percutaneous closure of LAA is safe and efficacious to prevent stroke in patients with NV-AF at high risk for cardioembolic events, with contraindications to anticoagulant therapy.