Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Registry of transcatheter aortic-valve implantation in high-risk patients.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2. METHODS: All TAVIs performed in France, as listed in the FRANCE 2 registry, were prospectively included in the study. The primary end point was death from any cause. RESULTS: A total of 3195 patients were enrolled between January 2010 and October 2011 at 34 centers. The mean (±SD) age was 82.7±7.2 years; 49% of the patients were women. All patients were highly symptomatic and were at high surgical risk for aortic-valve replacement. Edwards SAPIEN and Medtronic CoreValve devices were implanted in 66.9% and 33.1% of patients, respectively. Approaches were either transarterial (transfemoral, 74.6%; subclavian, 5.8%; and other, 1.8%) or transapical (17.8%). The procedural success rate was 96.9%. Rates of death at 30 days and 1 year were 9.7% and 24.0%, respectively. At 1 year, the incidence of stroke was 4.1%, and the incidence of periprosthetic aortic regurgitation was 64.5%. In a multivariate model, a higher logistic risk score on the European System for Cardiac Operative Risk Evaluation (EuroSCORE), New York Heart Association functional class III or IV symptoms, the use of a transapical TAVI approach, and a higher amount of periprosthetic regurgitation were significantly associated with reduced survival. CONCLUSIONS: This prospective registry study reflected real-life TAVI experience in high-risk elderly patients with aortic stenosis, in whom TAVI appeared to be a reasonable option. (Funded by Edwards Lifesciences and Medtronic.).

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial).

BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.

Rotational atherectomy as endovascular haute couture: a road map of tools and techniques for the interventional management of burr entrapment.

OBJECTIVES AND BACKGROUND: Rotational atherectomy (RA) is used as a debulking technique prior to stenting in some specialized cardiac centers for calcified coronary lesions amenable to percutaneous coronary intervention (PCI). A specific possible complication, burr entrapment, is unusual but carries serious risks and may sometimes necessitate surgery as a rescue procedure. However, different modalities using a percutaneous approach were proposed as a bail-out. We aim to propose a framework for possible management for trapped RA burr. METHODS AND RESULTS: A literature review of the most relevant cases of entrapped burr during PCI was performed. Twelve cases were reported and different solutions were discussed. Surgery was needed in only 1 patient to retrieve the trapped burr, and in all the other cases, different percutaneous solutions were successful to retract the trapped device. CONCLUSIONS: These cases illustrate that burr entrapment during RA, albeit rare, may occur and may transform a relatively simple PCI to a procedure failure. Although prevention is better than treatment, the operators should be aware of such serious complication and they should keep in mind that various possible percutaneous solutions may be successful to retrieve the burr and to avoid surgery.

Rotational atherectomy for left main coronary artery disease in octogenarians: transradial approach in a tertiary center and literature review.

OBJECTIVES: The aim of this study was to appreciate the safety and effectiveness of transradial percutaneous coronary intervention (PCI) with rotational atherectomy for highly calcified left main coronary artery (LMCA) disease in octogenarians. BACKGROUND: Conventional surgery is still considered the preferred management for LMCA disease; but, when the lesion is severely calcified, and the patient is unsuitable for surgery, the interventional cardiologist faces a complex PCI traditionally approached by femoral access. METHODS: Between June 2004 and December 2010, octogenarians with calcified LMCA disease who were primary denied for surgical revascularization were enrolled. Procedural success and major adverse cerebral and cardiovascular events (MACCE) including death, nonfatal myocardial infarction, target lesion revascularization (TLR), or stroke during long-term follow-up were evaluated. RESULTS: Forty-two consecutive patients ≥80 years had undergone stenting for calcified LMCA disease (13 with rotational atherectomy, the "Rota" group, and 29 without rotational atherectomy, the "without Rota" group). Procedural success was good (92.3% vs. 96.6%, respectively, p = NS). Mean follow-up time was 25.7 ± 21.4 and 28 ± 32.3 months, respectively. There was a TLR in 25% and 11.1%, respectively; p = NS. No difference was detected in terms of overall in-hospital or long-term mortality or MACCE. CONCLUSION: Rotational atherectomy followed by stent implantation by transradial approach, when applied to heavily calcified lesions, appeared to be a safe and effective strategy for the treatment of LMCA disease in octogenarians who were refused for surgery.

The prognostic value of the cardiopulmonary exercise test in patients with heart failure who have been treated with beta-blockers.

OBJECTIVES: The prevalence of chronic heart failure and a reduced ejection fraction (CHF-REF) has increased over the last decade. The cardiopulmonary exercise test (CPET) is an established tool for managing these patients. For patients who are administered beta-blockers, its predictive value is debated. The aim of this study was to assess the prognostic values of several parameters in patients with CHF-REF who were on beta-blockers. STUDY DESIGN: 390 patients with CHF-REF underwent CPET after cardiac rehabilitation and were followed for two years. RESULTS: The primary endpoints were all-cause mortality, cardiac-related mortality and major cardiovascular events (hospitalization for HF, heart transplantation and acute coronary syndrome or arrhythmia). The mean beta-blockers dosage was 68.9% of the target dose. The two-year mortality rate was 13%, while the mean age of the population was 57.1 years. In addition, most of the patients were men (85.5% vs. 14.5%). The resting LVEF was 35.7 ± 9.4 and the maximal oxygen uptake (peak VO2) was 19.5 ml/kg/min. The peak VO2, VE/VCO2 slope and circulatory power were significant predictors of risk. The prognosis was better when the initial linear VE/VCO2 slope was lower than 30, and the final steeper VE/VCO2 slope was lower than 32. There was no difference between the two slopes. The oxygen uptake efficiency slope, oxygen uptake, heart rate recovery, VE/VCO2/VO2 index and ventilatory threshold had no prognostic value. CONCLUSION: The peak VO2, circulatory power and VE/VCO2 slope were prognostic indicators for patients with CHF-REF who were on beta-blockers.

Thrombus-aspiration through 5 Fr guiding catheter with transradial approach in acute coronary syndromes: feasibility of a mini-invasive strategy.

OBJECTIVES: The purpose of this study was to assess the feasibility and safety of thrombus-aspiration through a 5 Fr guiding catheter with transradial approach in acute coronary syndromes. BACKGROUND: The use of thrombus-aspirating devices improves myocardial reperfusion but requires at least a 6 Fr guiding catheter. Transradial coronary interventions using a 5 Fr guiding catheter are attractive to reduce bleeding complications. METHODS: We retrospectively selected patients presenting acute coronary syndromes with angiographically visible thrombus who underwent thrombus-aspiration through radial access using a 4 Fr multipurpose catheter in a 5 Fr guiding catheter. We described clinical and angiographic characteristics of the cohort, and the procedure's technique, success and complications. RESULTS: Among the 34 included patients, 29 presented ST-segment elevation myocardial infarction. Complete resolution of the ST-segment elevation was effective in 93% of these patients. TIMI flow grade after thrombus-aspiration was significantly improved compared to baseline TIMI flow grade or after passage of the guidewire (P < 0.001 for both). There was no dissection or perforation but we noted distal embolization in 5 cases probably explained by the high grade of intracoronary thrombus in our cohort. CONCLUSION: Thrombus-aspiration through a 5 Fr guiding catheter with transradial approach seems to be safe and effective in selected patients with acute coronary syndrome. This mini-invasive approach brought the advantages of the transradial access in 5 Fr but also its limitations.

Percutaneous balloon atrioseptostomy for left heart discharge in extracorporeal life support patients with persistent pulmonary edema.

AIMS: In severe myocardial dysfunction, extracorporeal life support (ECLS) can preserve organ perfusion. Occasionally, the high resulting afterload can lead to refractory pulmonary edema. We report our experience with percutaneous balloon atrioseptostomy used in this circumstance to discharge the left heart and prevent worsening pulmonary congestion. METHODS AND RESULTS: Between October 2002 and December 2009, 5 patients, with a mean age of 39 years, who were under peripheral ECLS underwent percutaneous balloon atrioseptostomy for refractory worsening pulmonary edema as determined by clinical, radiological, and echocardiographic criteria. Myocardial dysfunction was related to drug poisoning in 2 cases and to myocarditis in the 3 others. Atrioseptostomy successfully improved pulmonary edema and echocardiographic indices of left ventricular function in all cases. Four patients were eventually discharged. The fifth patient died in hospital due to multiorgan failure. CONCLUSIONS: In our experience, percutaneous balloon atrioseptostomy appeared to be a rapid, effective, and minimally invasive technique for offloading the left heart of patients with a reversible cardiac dysfunction under ECLS and suffering from refractory pulmonary edema.

Prinzmetal angina or coronary spasm related to anaphylactoid reaction?

Prinzmetal's angina is a challenging diagnostic of spontaneous brief episodes of chest pain. Anaphylactoid reactions to radiocontrast media are immediate hypersensitivity responses that can mediate coronary artery spasm. Herein, we report the case of a 61-year-old man who underwent a coronary angiography for angina. The right coronary artery (RCA) was first visualized as normal, but during the left coronary system injections, he developed ST segment elevation and cardiogenic shock. No iatrogenic dissection of the left coronary system, which was initially normal, was displayed, but surprisingly, a retrograde supply to the RCA was visualized. Thus, we re-catheterized the RCA, which indicated a total occlusion of its second segment. Nitrate injections completely relieved the spasm and the clinical condition of the patient normalized. The possible related mechanisms are also discussed.

An alternative approach in tortuous coronary artery and distal stenosis during transradial percutaneous coronary intervention: deep engagement by a 5-Fr guiding catheter.

Transradial approach for percutaneous interventions has emerged as an alternative to transfemoral access which is known to be more associated with vascular local complications. However, lack of guiding-catheter support via the radial access is one of the problems encountering the operators. Many solutions have been proposed to overcome this problem. We report on a 62-year-old man with tight stenosis of the distal part of the right coronary artery. He underwent coronary angiography and then percutaneous angioplasty via the right radial artery. During the procedure, attempts to advance a stent beyond a tortuosity at the level of the second segment failed due to lack of support of the 6-Fr Judkins right 4 guiding catheter, even with the buddy wire technique. Then, switching to a 5-Fr Judkins right 4 guiding catheter allowed safe deep engagement and resulted in successful advancement and deployment of the stent.

Echocardiographic assessment of pulmonary vascular resistance in pulmonary arterial hypertension.

BACKGROUND: Echocardiographic ratio of peak tricuspid regurgitant velocity to the right ventricular outflow tract time-velocity integral (TRV/TVI rvot) was presented as a reliable non-invasive method of estimating pulmonary vascular resistance (PVR). Studies using this technique in patients with moderate to high PVR are scarce. Left ventricular outflow tract time-velocity integral (TVI lvot) can be easier to measure than TVI rvot, especially in patients with severe pulmonary hypertension (PH) with significant anatomical modifications of the right structures. AIMS: We wanted to determine whether the TRV/TVI rvot and TRV/TVI lvot ratios would form a reliable non-invasive tool to estimate PVR in a cohort of patients with moderate to severe pulmonary vascular disease. METHODS: Doppler echocardiographic examination and right heart catheterisation were performed in 37 patients. Invasive PVR was compared with TRV/TVI rvot and TRV/TVI lvot ratios using regression analysis. Two equations were modelled and the results compared with invasive measurements using the Bland-Altman analysis. Using receiver-operating characteristics curve analysis, a cut-off value for the two ratios was generated. RESULTS: Correlation coefficients between invasive PVR and TRV/TVI rvot then TRV/TVI lvot were respectively 0.76 and 0.74. Two new equations were found but the Bland-Altman analysis showed wide standard deviations (respectively 3.8 and 3.9 Wood units). A TRV/TVI rvot then TRV/TVI lvot ratio cut-off value of 0.14 had a sensitivity of 93% and a specificity of 57% for the first and a sensitivity of 87% and a specificity of 57% for the second to determine PVR > 2 Wood units. CONCLUSION: Echocardiography is useful for the screening of patients with pulmonary hypertension and PVR > 2 WU. It remains disappointing for accurate assessment of high PVR. TVI lvot may be an alternative to TVI rvot for patients for whom accurate TVI rvot measurement is not possible.

Snuggle T and protrusion (S-TAP) technique for coronary bifurcation stenting: A step-by-step angiographic and illustration demonstration.

T and small protrusion (TAP) is a stenting technique that is utilized for the management of coronary bifurcation lesions when using a two-stent strategy. This technique is also useful whenever stenting of a main vessel (MV) jeopardizes a side branch (SB) or when a sub-optimal result is encountered in a daughter vessel after starting with one-stent approach. The conversion from one-stent strategy to TAP could be achieved smoothly and often leads to good results. Technically, optimal positioning of the SB stent to achieve the required protrusion into the lumen of the MV remains a challenge. Toward that goal we propose an added step that involves inflating a balloon in the MV to serve as an anvil with simultaneous pullback of the SB stent, to be followed by stent deployment. We refer to this approach as the snuggle T and protrusion (S-TAP) technique owing to close contact between the SB stent and the MV balloon during simultaneous inflation. In this manuscript, we detail this interventional technique and provide a demonstrative case study.

Management of immediate partial bioresorbable vascular scaffold stent thrombosis.

Bioresorbable vascular scaffold (BVS) stents have been proposed recently as an elegant technique for treatment of coronary artery disease. However, perspective that these "dissolvable" stents will replace conventional metallic stents in broad spectrum of clinical conditions and patient categories in the near future has been moderated by non-negligible incidence of stent thrombosis (ST). Mechanical factors, such as strut thickness and malapposition have been implicated in increased risk of BVS ST. Presently described is case of immediate partial BVS ST in a young male related to technical procedural problem, rather than mechanical problem. Glycoprotein IIb/IIIa inhibitors associated with anticoagulation resulted in complete resolution of thrombus and facilitated successful patient outcome.

Cerebral microembolism during cardiac catheterization and risk of acute brain injury: a prospective diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Cerebral microembolism detected by transcranial Doppler occurs systematically during cardiac catheterization, but its clinical relevance remains unknown. Studies suggest that asymptomatic embolic cerebral infarction detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac interventions, especially after retrograde catheterization of the aortic valve in patients with valvular aortic stenosis, with a frequency as high as 22% of cases. We investigated the incidence of new ischemic lesions on serial cerebral DW MRI after cardiac catheterization. METHODS: This prospective study involved 46 patients with severe aortic valve stenosis. To assess the occurrence of cerebral infarction, all patients underwent cerebral DW MRI and neurological assessment within 24 hours before and 48 hours after cardiac catheterization and retrograde catheterization of the aortic valve. A subgroup was monitored by transcranial power M-mode Doppler during cardiac catheterization to observe cerebral blood flow and track emboli. RESULTS: One patient had a focal diffusion abnormality on DW MRI before cardiac catheterization. After catheterization, we detected only 1 additional acute cerebral diffusion abnormality in a single case (2.2%), although cerebral microemboli were detected in all transcranial Doppler-monitored patients during cardiac catheterization, as expected. All patients remained asymptomatic. Based on these results a mid-point incidence of 5.9% (95% CI, 0.01 to 12.5) for abnormalities on DW MRI in asymptomatic cardiac catheterization patients in our center can be assigned. CONCLUSIONS: Unsuspected cerebral infarctions can be detected by DW MRI after cardiac catheterization, but this phenomenon remains unfrequent in our series. Further studies are needed to identify factors explaining the discrepancy between these results and those of previous studies.

Clinical and angiographic analysis with a cobalt alloy coronary stent (driver) in stable and unstable angina pectoris.

The Clinical and Angiographic analysis with a Cobalt Alloy Coronary Stent (Driver) (CLASS) study was a prospective, nonrandomized, multicenter study designed to assess the safety and efficacy of a cobalt-chromium alloy-based stent in patients with stable or unstable angina pectoris. A total of 203 lesions were treated in 202 enrolled patients. The percentage of major adverse cardiac event-free patients was 87.6% (177 of 202) at 6 months (primary safety end point; major adverse cardiac events were defined as death, myocardial infarction, emergency bypass surgery, or target lesion revascularization [percutaneous transluminal coronary angioplasty or coronary artery bypass grafting]). The angiographic success rate (primary efficacy end point) was 100%, and the procedural success rate was 98%. The binary in-stent restenosis rate at 6 months was 12.6%. Our results have demonstrated that the Driver cobalt-chromium alloy stent can be used with a low 6-month incidence of major adverse cardiac events, a low 6-month binary restenosis rate, and high angiographic and procedural success rates.

Late Outcomes of Transcatheter Aortic Valve Replacement in High-Risk Patients: The FRANCE-2 Registry.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe complications have been assessed in relatively small populations and/or with limited follow-up. OBJECTIVES: This report details late clinical outcome and its determinants in the FRANCE-2 (FRench Aortic National CoreValve and Edwards) registry. METHODS: The FRANCE-2 registry prospectively included all TAVRs performed in France. Follow-up was scheduled at 30 days, at 6 months, and annually from 1 to 5 years. Standardized VARC (Valve Academic Research Consortium) outcome definitions were used. RESULTS: A total of 4,201 patients were enrolled between January 2010 and January 2012 in 34 centers. Approaches were transarterial (transfemoral 73%, transapical 18%, subclavian 6%, and transaortic or transcarotid 3%) or, in 18% of patients, transapical. Median follow-up was 3.8 years. Vital status was available for 97.2% of patients at 3 years. The 3-year all-cause mortality was 42.0% and cardiovascular mortality was 17.5%. In a multivariate model, predictors of 3-year all-cause mortality were male sex (p < 0.001), low body mass index, (p < 0.001), atrial fibrillation (p < 0.001), dialysis (p < 0.001), New York Heart Association functional class III or IV (p < 0.001), higher logistic EuroSCORE (p < 0.001), transapical or subclavian approach (p < 0.001 for both vs. transfemoral approach), need for permanent pacemaker implantation (p = 0.02), and post-implant periprosthetic aortic regurgitation grade ≥2 of 4 (p < 0.001). Severe events according to VARC criteria occurred mainly during the first month and subsequently in <2% of patients/year. Mean gradient, valve area, and residual aortic regurgitation were stable during follow-up. CONCLUSIONS: The FRANCE-2 registry represents the largest database available on late results of TAVR. Late mortality is largely related to noncardiac causes. Incidence rates of severe events are low after the first month. Valve performance remains stable over time.

Anomalous right coronary artery originating from the mid left anterior descending artery.

A 68-year-old male with a history of hypertension and hypercholesterolemia presented with recurrent episodes of chest discomfort. A 12-lead ECG and an echocardiogram were normal. A myocardial perfusion study could not rule out ischemia in the inferior wall. At coronary angiography using the transradial approach, the right coronary artery (RCA) could not be visualized. Angiography of the left coronary system demonstrated non-obstructive atherosclerosis involving the mid segment of the left anterior descending (LAD) artery and a normal circumflex (Cx) artery. The RCA originated from the mid LAD segment distal to the first septal perforator and the first diagonal branch and was free of atherosclerosis disease. A contrast-enhanced 64-slice multi-detector cardiac computed tomography showed that the LAD was severely calcified in the proximal part, and the RCA coursed anterior to the right ventricular outflow tract (RVOT) to reach the right atrioventricular groove. The patient was managed medically and became asymptomatic.

Antecubital vs Femoral Venous Access for Right Heart Catheterization: Benefits of a Flashback.

BACKGROUND: Although rare, complications of right heart catheterization (RHC) are usually related to the access site. Antecubital venous access for RHC allows immediate ambulation and may reduce access-site complications, but data on this approach are scarce. METHODS: Our study prospectively collected comprehensive data from consecutive RHCs performed at our academic center between February 2010 and August 2013. Demographic, procedural, and in-hospital outcomes were compared between patient groups defined by antecubital and femoral approaches. RESULTS: A total of 1007 RHC procedures was performed; 895 (88.9%) were performed through an antecubital approach and 112 (11.1%) were performed through a femoral approach. Antecubital attempts were successful in 92.8% of the clinically eligible patients. The antecubital approach was associated with a shorter procedure duration and fluoroscopy time as well as a lower radiation dose (P < 0.001 for all) compared with femoral access. Radiation dose and fluoroscopy time were significantly reduced (P < 0.001 for both) when antecubital procedures were performed by experienced operators compared with trainees. Periprocedural complications occurred in 8 patients (0.8%) (leading to prolonged hospitalization in only 1 patient in the femoral group). Access-site hematoma occurred more frequently in the femoral group (P < 0.001). CONCLUSIONS: An antecubital venous approach is a feasible alternative to femoral venous access for RHC. Shorter fluoroscopy time, lower radiation dose, and fewer access-site hematomas with this approach argue for its preferential use when possible and performed in an experienced centre.