Giovanni Pedrazzini

MitraClip® therapy in patients with end-stage systolic heart failure.

To assess the feasibility, short‐term durability and clinical outcomes of MitraClip® therapy for mitral regurgitation (MR) in patients with end‐stage heart failure and a severely reduced left ventricular (LV) ejection fraction.

Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial

CONTEXT The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). OBJECTIVE To compare stents eluting biolimus from a biodegradable polymer with bare-metal stents in primary PCI. DESIGN, SETTING, AND PATIENTS A prospective, randomized, single-blinded, controlled trial of 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19, 2009, and January 25, 2011. Clinical follow-up was performed at 1 and 12 months. INTERVENTION Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582). MAIN OUTCOME MEASURES Primary end point was the rate of major adverse cardiac events, a composite of cardiac death, target vessel-related reinfarction, and ischemia-driven target-lesion revascularization at 1 year. RESULTS Major adverse cardiac events at 1 year occurred in 24 patients (4.3%) receiving biolimus-eluting stents with biodegradable polymer and 49 patients (8.7%) receiving bare-metal stents (hazard ratio [HR], 0.49; 95% CI, 0.30-0.80; P = .004). The difference was driven by a lower risk of target vessel-related reinfarction (3 [0.5%] vs 15 [2.7%]; HR, 0.20; 95% CI, 0.06-0.69; P = .01) and ischemia-driven target-lesion revascularization (9 [1.6%] vs 32 [5.7%]; HR, 0.28; 95% CI, 0.13-0.59; P < .001) in patients receiving biolimus-eluting stents compared with those receiving bare-metal stents. Rates of cardiac death were not significantly different (16 [2.9%] vs 20 [3.5%], P = .53). Definite stent thrombosis occurred in 5 patients (0.9%) treated with biolimus-eluting stents and 12 patients (2.1%; HR, 0.42; 95% CI, 0.15-1.19; P = .10) treated with bare-metal stents. CONCLUSION Compared with a bare-metal stent, the use of biolimus-eluting stents with a biodegradable polymer resulted in a lower rate of the composite of major adverse cardiac events at 1 year among patients with STEMI undergoing primary PCI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00962416.

Drug-Eluting versus Bare-Metal Stents in Large Coronary Arteries

BACKGROUND Recent data have suggested that patients with coronary disease in large arteries are at increased risk for late cardiac events after percutaneous intervention with first-generation drug-eluting stents, as compared with bare-metal stents. We sought to confirm this observation and to assess whether this increase in risk was also seen with second-generation drug-eluting stents. METHODS We randomly assigned 2314 patients needing stents that were 3.0 mm or more in diameter to receive sirolimus-eluting, everolimus-eluting, or bare-metal stents. The primary end point was the composite of death from cardiac causes or nonfatal myocardial infarction at 2 years. Late events (occurring during months 7 to 24) and target-vessel revascularization were the main secondary end points. RESULTS The rates of the primary end point were 2.6% among patients receiving sirolimus-eluting stents, 3.2% among those receiving everolimus-eluting stents, and 4.8% among those receiving bare-metal stents, with no significant differences between patients receiving either drug-eluting stent and those receiving bare-metal stents. There were also no significant between-group differences in the rate of late events or in the rate of death, myocardial infarction, or stent thrombosis. Rates of target-vessel revascularization for reasons unrelated to myocardial infarction were 3.7% among patients receiving sirolimus-eluting stents, 3.1% among those receiving everolimus-eluting stents, and 8.9% among those receiving bare-metal stents. The rate of target-vessel revascularization was significantly reduced among patients receiving either drug-eluting stent, as compared with a bare-metal stent, with no significant difference between the two types of drug-eluting stents. CONCLUSIONS In patients requiring stenting of large coronary arteries, no significant differences were found among sirolimus-eluting, everolimus-eluting, and bare-metal stents with respect to the rate of death or myocardial infarction. With the two drug-eluting stents, similar reductions in rates of target-vessel revascularization were seen. (Funded by the Basel Cardiovascular Research Foundation and the Swiss National Foundation for Research; Current Controlled Trials number, ISRCTN72444640.).

Correction of Mitral Regurgitation in Nonresponders to Cardiac Resynchronization Therapy by MitraClip Improves Symptoms and Promotes Reverse Remodeling

OBJECTIVES This study evaluated the safety, efficacy, and effect of MitraClip treatment on symptoms and left ventricular (LV) remodeling in nonresponders to cardiac resynchronization therapy (CRT). BACKGROUND Moderate to severe functional mitral regurgitation (FMR) frequently persists after CRT, contributing to reduced or no response to CRT. Percutaneous repair with the MitraClip has been proposed as an additional therapeutic option in select patients with significant FMR. METHODS Fifty-one severely symptomatic CRT nonresponders with significant FMR (grade ≥2, 100%) underwent MitraClip treatment. Changes in New York Heart Association functional class, degree of FMR, LV ejection fraction (EF), and LV end-diastolic/end-systolic volumes (EDV/ESV) before and after (3, 6, and 12 months) MitraClip implantation were recorded. Mortality data, including cause of death, were collected. RESULTS MC treatment was feasible in all patients (49% 1 clip, 46% 2 clips). There were 2 periprocedural deaths. Median follow-up was 14 months (25th to 75th percentile: 8 to 17 months). New York Heart Association functional class improved acutely at discharge (73%) and continued to improve progressively during follow-up (regression model, p < 0.001). The proportion of patients with significant residual FMR (grade ≥2) progressively decreased during follow-up (regression model, p < 0.001). Reverse LV remodeling and improved LVEF were detected at 6 months, with further improvement at 12 months (regression model, p = 0.001, p = 0.008, and p = 0.031 for ESV, EDV, and LVEF, respectively). Overall 30-day mortality was 4.2%. Overall mortality during follow-up was 19.9 per 100 person-years (95% confidence interval: 10.3 to 38.3). Nonsurvivors had more compromised clinical baseline conditions, longer QRS duration, and a more dilated heart. CONCLUSIONS FMR treatment with the MitraClip in CRT nonresponders was feasible, safe, and demonstrated improved functional class, increased LVEF, and reduced ventricular volumes in about 70% of these study patients.

Supported High-Risk Percutaneous Coronary Intervention With the Impella 2.5 Device: The Europella Registry

OBJECTIVES This retrospective multicenter registry evaluated the safety and feasibility of left ventricular (LV) support with the Impella 2.5 (Abiomed Europe GmbH, Aachen, Germany) during high-risk percutaneous coronary intervention (PCI). BACKGROUND Patients with complex or high-risk coronary lesions, such as last remaining vessel or left main lesions, are increasingly being treated with PCI. Because periprocedural hemodynamic compromise and complications might occur rapidly, many of these high-risk procedures are being performed with mechanical cardiac assistance, particularly in patients with poor LV function. The Impella 2.5, a percutaneous implantable LV assist device, might be a superior alternative to the traditionally used intra-aortic balloon pump. METHODS The Europella registry included 144 consecutive patients who underwent a high-risk PCI. Safety and feasibility end points included incidence of 30-day adverse events and successful device function. RESULTS Patients were older (62% >70 years of age), 54% had an LV ejection fraction < or = 30%, and the prevalence of comorbid conditions was high. Mean European System for Cardiac Operative Risk Evaluation score was 8.2 (SD 3.4), and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. CONCLUSIONS This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI.

Timing and Magnitude of Regional Right Ventricular Function: A Speckle Tracking-Derived Strain Study of Normal Subjects and Patients with Right Ventricular Dysfunction

BACKGROUND The aim of this study was to evaluate the timing and magnitude of global and regional right ventricular (RV) function by means of speckle tracking-derived strain in normal subjects and patients with RV dysfunction. METHODS Peak longitudinal systolic strain (PLSS) and time to PLSS in 6 RV segments (the basal, mid, and apical segments of the RV free wall and septum) were obtained in 100 healthy volunteers and 76 patients with RV dysfunction by tracking speckles inside the myocardium using grayscale images. Global PLSS and time to PLSS were based on the average of the 6 regional values. RESULTS There was a significant and close correlation between RV contractility as measured by PLSS and tricuspid annular plane systolic excursion (r = -0.83, P < .001). In normal subjects, PLSS was significantly greater in the free wall than in the septum (-28.7 + or - 4.1% vs -19.8 + or - 3.4%, P < .001), whereas time to PLSS was similar in the different regions of the right ventricle. In patients with RV dysfunction, global and regional PLSS was significantly less than in normal subjects (-13.7 + or - 3.6% vs -24.2 + or - 2.9%, P < .001), and a global PLSS cutoff value of -19% was helpful in distinguishing the two groups. Furthermore, time to PLSS in all of the RV septal segments and dispersion in RV contraction timing were significantly longer. Global PLSS in the patients with RV dysfunction was also significantly less in the presence of moderate to severe pulmonary hypertension (-12.7 + or - 3.6% vs -14.4 + or - 3.4%, P = .038). CONCLUSIONS Speckle tracking not only makes it possible to quantify global RV function but also illustrates the physiology of RV contraction and the pattern of activation at regional level. Speckle tracking-derived strain could become an important new means of assessing and following up patients with impaired RV function and increased pulmonary pressure.

Randomized Comparison of a Titanium-Nitride-Oxide–Coated Stent With a Stainless Steel Stent for Coronary Revascularization The TiNOX Trial

Background—Stent coating with titanium-nitride-oxide has been shown to reduce neointimal hyperplasia in the porcine restenosis model. We designed a prospective, randomized, clinical study to investigate the safety and efficacy of titanium-nitride-oxide–coated stents compared with stainless steel stents. Methods and Results—Ninety-two patients with de novo lesions were randomly assigned to treatment with titanium-nitride-oxide–coated stents (n=45) or stainless steel stents of otherwise identical design (n=47; control). Baseline characteristics were similar in both groups. At 30 days, no stent thromboses or other adverse events had occurred in either group. Quantitative coronary angiography at 6 months revealed lower late loss (0.55±0.63 versus 0.90±0.76 mm, P=0.03) and percent diameter stenosis (26±17% versus 36±24%, P=0.04) in lesions treated with titanium-nitride oxide–coated than in control stents. Binary restenosis was reduced from 33% in the control group to 15% in the titanium-nitride oxide–coated stent group (P=0.07). Intravascular ultrasound studies at 6 months showed smaller neointimal volume in titanium-nitride-oxide–coated stents than in control stents (18±21 versus 48±28 mm3, P<0.0001). Major adverse cardiac events at 6 months were less frequent in titanium-nitride-oxide–coated stents than in control stent–treated patients (7% versus 27%, P=0.02), largely driven by a reduced need for target-lesion revascularization (7% versus 23%, P=0.07). Conclusions—Revascularization with titanium-nitride-oxide–coated stents is safe and effective in patients with de novo native coronary artery lesions. Titanium-nitride-oxide–coated stents reduce restenosis and major adverse cardiac events compared with stainless steel stents of otherwise identical design.

Percutaneous Left Ventricular Support With the Impella 2.5 Assist Device in Acute Cardiogenic Shock - Results of the Impella EUROSHOCK-Registry

Background— Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella–EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5–percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. Methods and Results— This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5–percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5–percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. Conclusions— In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5–treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5–application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5–support in this high-risk patient group.

Evaluation of the left atrial appendage with real-time 3-dimensional transesophageal echocardiography: implications for catheter-based left atrial appendage closure.

Background— Precise knowledge of left atrial appendage (LAA) orifice size is crucial for correct sizing of LAA closure devices. The aim of the present study was to determine the performance of real-time 3D transesophageal echocardiography (RT3DTEE) for LAA orifice size assessment, compared with 2D transesophageal echocardiography (2DTEE), and to investigate the impact of atrial fibrillation (AF) on LAA orifice size. Methods and Results— One hundred thirty-seven patients (38 control subjects, 31 with paroxysmal AF, 38 with persistent AF and 30 with permanent AF) underwent 2DTEE and RT3DTEE. Both techniques were used to measure LAA orifice area. Clinically-indicated 64-slice computed tomography (CT) was used as reference technique in 46 patients. Two-dimensional TEE underestimated LAA orifice area, compared with RT3DTEE (1.99±0.94 cm2 versus 3.05±1.27 cm2; P <0.001). RT3DTEE showed higher correlation with CT for the assessment of LAA orifice area, compared with 2DTEE ( r =0.92; 95% confidence interval, 0.85 to 0.95, versus r =0.72; 95% confidence interval, 0.54 to 0.83, respectively). At Bland–Altman analysis, RT3DTEE and 2DTEE underestimated LAA orifice area, compared with CT. However, RT3DTEE showed smaller bias (0.07 cm2 versus 0.72 cm2) and narrower limits of agreement (−0.71 to 0.85 cm2 versus −0.58 to 2.02 cm2) with CT, compared with 2DTEE. Among AF patients, a progressive increase in RT3DTEE-derived LAA orifice area was observed with increasing frequency of AF ( P <0.001). At multivariate analysis, AF and left atrial volume index ( P <0.001 for both) were independently associated with RT3DTEE-derived LAA orifice area. Conclusions— RT3DTEE is more accurate than 2DTEE for the assessment of LAA orifice size. A progressive increase in LAA orifice area is observed with increasing frequency of AF.Background— Precise knowledge of left atrial appendage (LAA) orifice size is crucial for correct sizing of LAA closure devices. The aim of the present study was to determine the performance of real-time 3D transesophageal echocardiography (RT3DTEE) for LAA orifice size assessment, compared with 2D transesophageal echocardiography (2DTEE), and to investigate the impact of atrial fibrillation (AF) on LAA orifice size. Methods and Results— One hundred thirty-seven patients (38 control subjects, 31 with paroxysmal AF, 38 with persistent AF and 30 with permanent AF) underwent 2DTEE and RT3DTEE. Both techniques were used to measure LAA orifice area. Clinically-indicated 64-slice computed tomography (CT) was used as reference technique in 46 patients. Two-dimensional TEE underestimated LAA orifice area, compared with RT3DTEE (1.99±0.94 cm2 versus 3.05±1.27 cm2; P<0.001). RT3DTEE showed higher correlation with CT for the assessment of LAA orifice area, compared with 2DTEE (r=0.92; 95% confidence interval, 0.85 to 0.95, versus r=0.72; 95% confidence interval, 0.54 to 0.83, respectively). At Bland–Altman analysis, RT3DTEE and 2DTEE underestimated LAA orifice area, compared with CT. However, RT3DTEE showed smaller bias (0.07 cm2 versus 0.72 cm2) and narrower limits of agreement (−0.71 to 0.85 cm2 versus −0.58 to 2.02 cm2) with CT, compared with 2DTEE. Among AF patients, a progressive increase in RT3DTEE-derived LAA orifice area was observed with increasing frequency of AF (P<0.001). At multivariate analysis, AF and left atrial volume index (P<0.001 for both) were independently associated with RT3DTEE-derived LAA orifice area. Conclusions— RT3DTEE is more accurate than 2DTEE for the assessment of LAA orifice size. A progressive increase in LAA orifice area is observed with increasing frequency of AF.

Predictors for efficacy of percutaneous mitral valve repair using the MitraClip system: the results of the MitraSwiss registry

Background Percutaneous mitral valve repair (MVR) using the MitraClip system has become a valid alternative for patients with severe mitral regurgitation (MR) and high operative risk. Objective To identify clinical and periprocedural factors that may have an impact on clinical outcome. Design Multi-centre longitudinal cohort study. Setting Tertiary referral centres. Patients Here we report on the first 100 consecutive patients treated with percutaneous MVR in Switzerland between March 2009 and April 2011. All of them had moderate–severe (3+) or severe (4+) MR, and 62% had functional MR. 82% of the patients were in New York Heart Association (NYHA) class III/IV, mean left ventricular ejection fraction was 48% and the median European System for Cardiac Operative Risk Evaluation was 16.9%. Interventions MitraClip implantation performed under echocardiographic and fluoroscopic guidance in general anaesthesia. Main outcome measures Clinical, echocardiographic and procedural data were prospectively collected. Results Acute procedural success (APS, defined as successful clip implantation with residual MR grade ≤2+) was achieved in 85% of patients. Overall survival at 6 and 12 months was 89.9% (95% CI 81.8 to 94.6) and 84.6% (95% CI 74.7 to 91.0), respectively. Univariate Cox regression analysis identified APS (p=0.0069) and discharge MR grade (p=0.03) as significant predictors of survival. Conclusions In our consecutive cohort of patients, APS was achieved in 85%. APS and residual discharge MR grade are important predictors of mid-term survival after percutaneous MVR.