Transcatheter closure of coronary artery fistulas has emerged as a successful alternative to surg... more Transcatheter closure of coronary artery fistulas has emerged as a successful alternative to surgery. We describe various techniques and short-term findings in 15 patients who were taken up for transcatheter closure of these fistulas. Fifteen patients (aged 2-55 years; 12 males) with coronary artery fistulas underwent percutaneous transcatheter closure between June 1997 and December 2002. Site of origin of these fistulas were: right coronary artery in 7, left anterior descending coronary artery in 4, left main coronary artery in 2 and left circumflex coronary artery in 2 patients. Drainage site of these fistulas were: right ventricle in 9, right atrium in 4 and pulmonary artery in 2 patients. Out of these 15 fistulas, 14 were congenital and one was iatrogenically produced following inadvertent cutting balloon angioplasty of a septal perforator in a patient with chronic total occlusion of left anterior descending coronary artery. Various occlusion devices used to close these fistulas were: conventional metallic coils in 10, floppy tips of coronary angioplasty guidewires in 2, Amplatzer duct occluder in 1 and Amplatzer septal occluder in 2 patients. One of our patients had a coronary artery fistula draining by two openings into the right atrium, both of which were successfully closed using 2 Amplatzer duct occluders. Check angiogram after the procedure revealed complete occlusion in 13 (86.6%) and small residual flow in 2 patients. Follow-up studies at 3-55 months (mean 18 months) showed complete abolition of shunt in all patients with no evidence of recanalization leading to recurrence of shunt. Transcatheter closure of coronary artery fistulas is feasible and safe in the anatomically suitable vessels. Use of floppy tips of coronary angioplasty guidewires reduces the cost of the procedure significantly. which is an important consideration in developing countries like India.
The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicated devi... more The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicated device for percutaneous left atrial appendage (LAA) occlusion. The new device has been designed to facilitate the implantation process, improve the sealing performance and further reduce the risk of complications. The objective of the study was to describe the initial experience with the Amplatzer Amulet for percutaneous LAA occlusion. This was a prospective single-center study of patients undergoing percutaneous LAA occlusion. The indication for LAA closure was a formal contraindication for oral anticoagulation or previous history of stroke due to INR lability. All procedures were done under general anesthesia and transesophageal echocardiography (TEE) guidance. Transthoracic echocardiography was performed 24h after the procedure in order to rule out procedural complications before discharge. Further follow-up was done with a clinical visit and TEE at 1-3 months. Between July-2012 and June-2013, 25 patients with a mean CHA2DS2-VASC of 4.3 ± 1.7 underwent LAA occlusion with the Amplatzer Amulet. The device was successfully implanted in 24 patients (96%) without any procedural stroke, pericardial effusion or device embolization. None of the patients presented any clinical event at follow-up. Follow-up TEE showed complete LAA sealing in all patients with no residual leaks >3mm and no device embolization. One patient (4.1%) presented a device thrombosis at follow-up without clinical expression. In this initial series of patients, the Amulet showed a remarkable acute and short-term performance in terms of feasibility and safety as depicted by the high successful implantation rate and the low incidence of complications.
Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensio... more Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensional transesophageal echocardiographic (TEE) method to localize mitral periprosthetic leaks (PPLs) for transcatheter reduction.
Atrial septal defect is a common congenital heart defect. In the late 1990s, percutaneous closure... more Atrial septal defect is a common congenital heart defect. In the late 1990s, percutaneous closure became available and eventually the treatment of choice. The procedure is considered safe because of its low incidence of complications. Infection rate is extremely low and occurs typically early after device implantation. Herein we present a case of late and dramatic infection of an Amplatzer Septal Occluder (St Jude Medical). This case illustrates that infection remains possible a long time after atrial septal defect occlusion despite theoretical device endothelialization.
Background—The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasou... more Background—The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS) for the assessment of progression/regression in coronary artery disease are uncertain. To explore this subject further, we analyzed the angiographic and IVUS data derived from a contemporary clinical trial population. Methods and Results—We investigated the relationships between QCA and IVUS at single time points (n525) and also for
Background: Several studies have shown an association of cryptogenic stroke and embolism with pat... more Background: Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods: The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion: patients were randomized in 29 centers
Journal of the American College of Cardiology, 2008
The objective of this study was to compare the level of platelet inhibition achieved by 3 differe... more The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate.
Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensio... more Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensional transesophageal echocardiographic (TEE) method to localize mitral periprosthetic leaks (PPLs) for transcatheter reduction.
More than 1 million percutaneous coronary interventions (PCIs) are performed yearly worldwide. Re... more More than 1 million percutaneous coronary interventions (PCIs) are performed yearly worldwide. Restenosis is the recurrent narrowing that can occur within 6 months following an initially successful PCI. Although drug-eluting stents have accomplished remarkable success, restenosis has not been eliminated and optimisation of both the polymers and drugs associated with them is desirable. This article reviews the presently available and potential preventive approaches against restenosis, including the sirolimus and paclitaxel drug-eluting stents.
Aims/hypothesis We sought to understand the relationships between glycaemic status and both sever... more Aims/hypothesis We sought to understand the relationships between glycaemic status and both severity and progression of coronary artery disease (CAD), the leading cause of death in diabetes. Methods Baseline fasting blood glucose (FBG) and HbA 1c (%) were measured in 426 patients with known or suspected stable CAD, who underwent coronary artery intravascular ultrasound (IVUS) at baseline and after a mean follow-up period of 664 days (range 257 to 961). The patients were categorised as normoglycaemic (n=226, 53%), or as having impaired fasting glucose (n=118, 28%) or diabetes (n=82, 19%). Results The maximum percentage coronary atheroma area at baseline was greater in diabetic patients (73.33±8.86%) than in those with normoglycaemia (69.08±10.43%; p=0.001) and impaired fasting glucose (69.32±9.59%; p=0.0031). In averaged IVUS measurements of the 30-mm target segment (n=332 participants), change in percentage atheroma area during follow-up was also greater in the diabetes (1.86± 3.90%) than in other groups (0.28±3.32% and 0.56±2.96%, p=0.0047 global). FBG correlated with maximum percentage atheroma area at baseline (r=0.17; p=0.0003). HbA 1c also correlated with maximum percentage atheroma area at baseline (r=0.26; p=0.0001) and with change in maximum plaque area (r=0.16; p=0.016). A similar pattern of results occurred with plaque volume. The relationships between diabetes or HbA 1c and both IVUS measurements of plaque burden and remodelling persisted after adjustment. Conclusions/interpretation Fasting blood glucose, HbA 1c and the presence of diabetes are associated with the severity and progression of coronary atherosclerosis. These observations support the hypothesis that better glycaemic control may favourably influence CAD in patients with abnormal glucose tolerance or diabetes.
In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidativ... more In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidative stress in patients with decompensated CHF (congestive heart failure) and assessed whether clinical recompensation by short-term inotropic therapy influences these parameters. Patients with worsening CHF (n=29, aged 61.9+/-2.7 years), NYHA (New York Heart Association) class III-IV, and left ventricular ejection fraction of 23.7+/-1.8% were studied. Controls comprised age-matched healthy volunteers (n=15; 54.1+/-3.2 years). Plasma levels of cytokines [IL (interleukin)-6 and IL-18], chemokines [MCP-1 (monocyte chemotactic protein-1)], adhesion molecules [sICAM (soluble intercellular adhesion molecule), sE-selectin (soluble E-selectin)], systemic markers of oxidation [TBARS (thiobarbituric acid-reactive substances), 8-isoprostaglandin F(2alpha) and nitrotyrosine] and hs-CRP (high-sensitivity C-reactive protein) were measured by ELISA and colorimetric assays at admission and 30 days following 72-h milrinone (n=15) or dobutamine (n=14) infusion. Plasma IL-6, IL-18, sICAM, E-selectin, hs-CRP and oxidative markers were significantly higher in patients on admission before inotropic treatment compared with controls (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Short-term inotropic support improved clinical status as assessed by NYHA classification and by the 6-min walk test and significantly decreased plasma levels of IL-6, IL-18, sICAM, hs-CRP and markers of oxidation (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) at 30 days. The effects of milrinone and dobutamine were similar. In conclusion, our results demonstrate that patients with decompensated CHF have marked systemic inflammation and increased production of oxygen free radicals. Short-term inotropic support improves functional status and reduces indices of inflammation and oxidative stress in patients with decompensated CHF.
Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic p... more Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor. In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks. The primary study end point, whole blood stimulated leukotriene LTB4 at trough drug level, was reduced in all VIA-2291 groups (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) in a dose-dependent fashion, with approximately 80% inhibition in &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;90% of patients in the 100-mg group. A significant reduction of urine leukotriene LTE4 was obtained in all dose groups. No serious adverse events were considered related to study drug. A subset of 93 patients who had undergone a 64-slice coronary CT examination at baseline continued on study medication for a total of 24 weeks and underwent a repeat scan. Five of these patients withdrew or were noncompliant and 28 had nonevaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo-treated patients and in 2 of 42 (4.8%) VIA-2291-treated patients (P=0.01). A reduction in noncalcified plaque volume at 24 weeks versus placebo was observed in VIA-2291-treated groups in the 34 of these 60 patients in whom this end point was analyzable (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). VIA-2291 reduces leukotriene production at 12 weeks after an acute coronary syndrome. Preliminary data from the CT substudy suggest that such a reduction in leukotriene production may influence atherosclerosis; however, this requires confirmation in a larger study. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.
Background-The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasou... more Background-The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS) for the assessment of progression/regression in coronary artery disease are uncertain. To explore this subject further, we analyzed the angiographic and IVUS data derived from a contemporary clinical trial population. Methods and Results-We investigated the relationships between QCA and IVUS at single time points (nϭ525) and also for the changes over time (nϭ432). QCA and IVUS data underwent central laboratory analyses. Statistically significant correlations were observed between the QCA coronary artery score and the IVUS-derived lumen volume (rϭ0.65, PϽ0.0001) and total vessel volume (rϭ0.55, PϽ0.0001) and between the QCA cumulative coronary stenosis score and percent atheroma volume on IVUS (rϭ0.32, PϽ0.0001) at baseline for matched segments. A similar pattern of correlations was observed for global (all segments) QCA-derived and single-vessel IVUS-derived data. There were statistically significant but weak correlations between the changes over time in lumen dimensions on QCA and IVUS (Pϭ0.005) and between the change in cumulative coronary stenosis score on QCA and percent atheroma volume on IVUS (rϭ0.14, Pϭ0.01). Nevertheless, patients with and without angiographic progression had changes in plaque volume on IVUS of 9.13 and 0.20 mm 3 , respectively (Pϭ0.028).
Background-Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may preven... more Background-Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis. Methods and Results-This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level Ͻ125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was Ϸ200 mm 3 , and the least squares mean change at end of treatment was 0.7 mm 3 for placebo and 7.7, 4.1, and 4.8 mm 3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted Pϭ0.17 [unadjusted Pϭ0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (PϭNS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (PϽ0.05 in all groups).
Effective closure performance for patent foramen ovale (PFO) has been suggested to be one of the ... more Effective closure performance for patent foramen ovale (PFO) has been suggested to be one of the factors that plays a relevant role in future clinical outcomes after stroke or transient ischemic attack. Between January 2009 and June 2012, all consecutive patients undergoing transcatheter PFO closure in our institution using the Amplatzer PFO Occluder (APO) (St Jude Medical, St Paul, MN), BioSTAR (NMT Medical Inc, Boston, MA), GORE HELEX (HELEX) (W.L. Gore &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Associates, Newark, DE), and GORE Septal Occluder (GSO) (W.L. Gore &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Associates) were included. Closure performance was assessed using transesophageal echocardiography 4 months after the index procedure. One hundred ninety-three patients were included in the study. Patient distribution was as follows: (1) 48 GSO (24.8%); (2) 34 HELEX (17.6%); (3) 74 APO (38.3%); and (4) 37 BioSTAR (19.1%). No complications occurred during device implantation. During clinical follow-up (20.8 ± 13.2 months), 2 (1.1%) patients had a stroke, 3 (1.7%) patients had a peripheral embolism, and 8 (4.7%) patients presented with a documented atrial arrhythmia. There were no significant differences in clinical outcomes among the devices. Transesophageal echocardiography follow-up revealed higher closure rates with GSO (92.6%) and BioSTAR (93.7%) compared with HELEX (74.2%; P = 0.031 and P = 0.034, respectively) and APO (76.4%; P = 0.036 and P = 0.041, respectively). The GSO and BioSTAR showed better closure rates than HELEX and APO at 4 months. PFO closure is a safe procedure with a low rate of clinical events at follow-up.
Transcatheter closure of coronary artery fistulas has emerged as a successful alternative to surg... more Transcatheter closure of coronary artery fistulas has emerged as a successful alternative to surgery. We describe various techniques and short-term findings in 15 patients who were taken up for transcatheter closure of these fistulas. Fifteen patients (aged 2-55 years; 12 males) with coronary artery fistulas underwent percutaneous transcatheter closure between June 1997 and December 2002. Site of origin of these fistulas were: right coronary artery in 7, left anterior descending coronary artery in 4, left main coronary artery in 2 and left circumflex coronary artery in 2 patients. Drainage site of these fistulas were: right ventricle in 9, right atrium in 4 and pulmonary artery in 2 patients. Out of these 15 fistulas, 14 were congenital and one was iatrogenically produced following inadvertent cutting balloon angioplasty of a septal perforator in a patient with chronic total occlusion of left anterior descending coronary artery. Various occlusion devices used to close these fistulas were: conventional metallic coils in 10, floppy tips of coronary angioplasty guidewires in 2, Amplatzer duct occluder in 1 and Amplatzer septal occluder in 2 patients. One of our patients had a coronary artery fistula draining by two openings into the right atrium, both of which were successfully closed using 2 Amplatzer duct occluders. Check angiogram after the procedure revealed complete occlusion in 13 (86.6%) and small residual flow in 2 patients. Follow-up studies at 3-55 months (mean 18 months) showed complete abolition of shunt in all patients with no evidence of recanalization leading to recurrence of shunt. Transcatheter closure of coronary artery fistulas is feasible and safe in the anatomically suitable vessels. Use of floppy tips of coronary angioplasty guidewires reduces the cost of the procedure significantly. which is an important consideration in developing countries like India.
The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicated devi... more The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicated device for percutaneous left atrial appendage (LAA) occlusion. The new device has been designed to facilitate the implantation process, improve the sealing performance and further reduce the risk of complications. The objective of the study was to describe the initial experience with the Amplatzer Amulet for percutaneous LAA occlusion. This was a prospective single-center study of patients undergoing percutaneous LAA occlusion. The indication for LAA closure was a formal contraindication for oral anticoagulation or previous history of stroke due to INR lability. All procedures were done under general anesthesia and transesophageal echocardiography (TEE) guidance. Transthoracic echocardiography was performed 24h after the procedure in order to rule out procedural complications before discharge. Further follow-up was done with a clinical visit and TEE at 1-3 months. Between July-2012 and June-2013, 25 patients with a mean CHA2DS2-VASC of 4.3 ± 1.7 underwent LAA occlusion with the Amplatzer Amulet. The device was successfully implanted in 24 patients (96%) without any procedural stroke, pericardial effusion or device embolization. None of the patients presented any clinical event at follow-up. Follow-up TEE showed complete LAA sealing in all patients with no residual leaks &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3mm and no device embolization. One patient (4.1%) presented a device thrombosis at follow-up without clinical expression. In this initial series of patients, the Amulet showed a remarkable acute and short-term performance in terms of feasibility and safety as depicted by the high successful implantation rate and the low incidence of complications.
Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensio... more Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensional transesophageal echocardiographic (TEE) method to localize mitral periprosthetic leaks (PPLs) for transcatheter reduction.
Atrial septal defect is a common congenital heart defect. In the late 1990s, percutaneous closure... more Atrial septal defect is a common congenital heart defect. In the late 1990s, percutaneous closure became available and eventually the treatment of choice. The procedure is considered safe because of its low incidence of complications. Infection rate is extremely low and occurs typically early after device implantation. Herein we present a case of late and dramatic infection of an Amplatzer Septal Occluder (St Jude Medical). This case illustrates that infection remains possible a long time after atrial septal defect occlusion despite theoretical device endothelialization.
Background—The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasou... more Background—The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS) for the assessment of progression/regression in coronary artery disease are uncertain. To explore this subject further, we analyzed the angiographic and IVUS data derived from a contemporary clinical trial population. Methods and Results—We investigated the relationships between QCA and IVUS at single time points (n525) and also for
Background: Several studies have shown an association of cryptogenic stroke and embolism with pat... more Background: Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods: The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion: patients were randomized in 29 centers
Journal of the American College of Cardiology, 2008
The objective of this study was to compare the level of platelet inhibition achieved by 3 differe... more The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate.
Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensio... more Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensional transesophageal echocardiographic (TEE) method to localize mitral periprosthetic leaks (PPLs) for transcatheter reduction.
More than 1 million percutaneous coronary interventions (PCIs) are performed yearly worldwide. Re... more More than 1 million percutaneous coronary interventions (PCIs) are performed yearly worldwide. Restenosis is the recurrent narrowing that can occur within 6 months following an initially successful PCI. Although drug-eluting stents have accomplished remarkable success, restenosis has not been eliminated and optimisation of both the polymers and drugs associated with them is desirable. This article reviews the presently available and potential preventive approaches against restenosis, including the sirolimus and paclitaxel drug-eluting stents.
Aims/hypothesis We sought to understand the relationships between glycaemic status and both sever... more Aims/hypothesis We sought to understand the relationships between glycaemic status and both severity and progression of coronary artery disease (CAD), the leading cause of death in diabetes. Methods Baseline fasting blood glucose (FBG) and HbA 1c (%) were measured in 426 patients with known or suspected stable CAD, who underwent coronary artery intravascular ultrasound (IVUS) at baseline and after a mean follow-up period of 664 days (range 257 to 961). The patients were categorised as normoglycaemic (n=226, 53%), or as having impaired fasting glucose (n=118, 28%) or diabetes (n=82, 19%). Results The maximum percentage coronary atheroma area at baseline was greater in diabetic patients (73.33±8.86%) than in those with normoglycaemia (69.08±10.43%; p=0.001) and impaired fasting glucose (69.32±9.59%; p=0.0031). In averaged IVUS measurements of the 30-mm target segment (n=332 participants), change in percentage atheroma area during follow-up was also greater in the diabetes (1.86± 3.90%) than in other groups (0.28±3.32% and 0.56±2.96%, p=0.0047 global). FBG correlated with maximum percentage atheroma area at baseline (r=0.17; p=0.0003). HbA 1c also correlated with maximum percentage atheroma area at baseline (r=0.26; p=0.0001) and with change in maximum plaque area (r=0.16; p=0.016). A similar pattern of results occurred with plaque volume. The relationships between diabetes or HbA 1c and both IVUS measurements of plaque burden and remodelling persisted after adjustment. Conclusions/interpretation Fasting blood glucose, HbA 1c and the presence of diabetes are associated with the severity and progression of coronary atherosclerosis. These observations support the hypothesis that better glycaemic control may favourably influence CAD in patients with abnormal glucose tolerance or diabetes.
In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidativ... more In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidative stress in patients with decompensated CHF (congestive heart failure) and assessed whether clinical recompensation by short-term inotropic therapy influences these parameters. Patients with worsening CHF (n=29, aged 61.9+/-2.7 years), NYHA (New York Heart Association) class III-IV, and left ventricular ejection fraction of 23.7+/-1.8% were studied. Controls comprised age-matched healthy volunteers (n=15; 54.1+/-3.2 years). Plasma levels of cytokines [IL (interleukin)-6 and IL-18], chemokines [MCP-1 (monocyte chemotactic protein-1)], adhesion molecules [sICAM (soluble intercellular adhesion molecule), sE-selectin (soluble E-selectin)], systemic markers of oxidation [TBARS (thiobarbituric acid-reactive substances), 8-isoprostaglandin F(2alpha) and nitrotyrosine] and hs-CRP (high-sensitivity C-reactive protein) were measured by ELISA and colorimetric assays at admission and 30 days following 72-h milrinone (n=15) or dobutamine (n=14) infusion. Plasma IL-6, IL-18, sICAM, E-selectin, hs-CRP and oxidative markers were significantly higher in patients on admission before inotropic treatment compared with controls (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Short-term inotropic support improved clinical status as assessed by NYHA classification and by the 6-min walk test and significantly decreased plasma levels of IL-6, IL-18, sICAM, hs-CRP and markers of oxidation (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) at 30 days. The effects of milrinone and dobutamine were similar. In conclusion, our results demonstrate that patients with decompensated CHF have marked systemic inflammation and increased production of oxygen free radicals. Short-term inotropic support improves functional status and reduces indices of inflammation and oxidative stress in patients with decompensated CHF.
Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic p... more Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor. In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks. The primary study end point, whole blood stimulated leukotriene LTB4 at trough drug level, was reduced in all VIA-2291 groups (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) in a dose-dependent fashion, with approximately 80% inhibition in &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;90% of patients in the 100-mg group. A significant reduction of urine leukotriene LTE4 was obtained in all dose groups. No serious adverse events were considered related to study drug. A subset of 93 patients who had undergone a 64-slice coronary CT examination at baseline continued on study medication for a total of 24 weeks and underwent a repeat scan. Five of these patients withdrew or were noncompliant and 28 had nonevaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo-treated patients and in 2 of 42 (4.8%) VIA-2291-treated patients (P=0.01). A reduction in noncalcified plaque volume at 24 weeks versus placebo was observed in VIA-2291-treated groups in the 34 of these 60 patients in whom this end point was analyzable (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). VIA-2291 reduces leukotriene production at 12 weeks after an acute coronary syndrome. Preliminary data from the CT substudy suggest that such a reduction in leukotriene production may influence atherosclerosis; however, this requires confirmation in a larger study. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.
Background-The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasou... more Background-The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS) for the assessment of progression/regression in coronary artery disease are uncertain. To explore this subject further, we analyzed the angiographic and IVUS data derived from a contemporary clinical trial population. Methods and Results-We investigated the relationships between QCA and IVUS at single time points (nϭ525) and also for the changes over time (nϭ432). QCA and IVUS data underwent central laboratory analyses. Statistically significant correlations were observed between the QCA coronary artery score and the IVUS-derived lumen volume (rϭ0.65, PϽ0.0001) and total vessel volume (rϭ0.55, PϽ0.0001) and between the QCA cumulative coronary stenosis score and percent atheroma volume on IVUS (rϭ0.32, PϽ0.0001) at baseline for matched segments. A similar pattern of correlations was observed for global (all segments) QCA-derived and single-vessel IVUS-derived data. There were statistically significant but weak correlations between the changes over time in lumen dimensions on QCA and IVUS (Pϭ0.005) and between the change in cumulative coronary stenosis score on QCA and percent atheroma volume on IVUS (rϭ0.14, Pϭ0.01). Nevertheless, patients with and without angiographic progression had changes in plaque volume on IVUS of 9.13 and 0.20 mm 3 , respectively (Pϭ0.028).
Background-Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may preven... more Background-Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis. Methods and Results-This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level Ͻ125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was Ϸ200 mm 3 , and the least squares mean change at end of treatment was 0.7 mm 3 for placebo and 7.7, 4.1, and 4.8 mm 3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted Pϭ0.17 [unadjusted Pϭ0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (PϭNS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (PϽ0.05 in all groups).
Effective closure performance for patent foramen ovale (PFO) has been suggested to be one of the ... more Effective closure performance for patent foramen ovale (PFO) has been suggested to be one of the factors that plays a relevant role in future clinical outcomes after stroke or transient ischemic attack. Between January 2009 and June 2012, all consecutive patients undergoing transcatheter PFO closure in our institution using the Amplatzer PFO Occluder (APO) (St Jude Medical, St Paul, MN), BioSTAR (NMT Medical Inc, Boston, MA), GORE HELEX (HELEX) (W.L. Gore &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Associates, Newark, DE), and GORE Septal Occluder (GSO) (W.L. Gore &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Associates) were included. Closure performance was assessed using transesophageal echocardiography 4 months after the index procedure. One hundred ninety-three patients were included in the study. Patient distribution was as follows: (1) 48 GSO (24.8%); (2) 34 HELEX (17.6%); (3) 74 APO (38.3%); and (4) 37 BioSTAR (19.1%). No complications occurred during device implantation. During clinical follow-up (20.8 ± 13.2 months), 2 (1.1%) patients had a stroke, 3 (1.7%) patients had a peripheral embolism, and 8 (4.7%) patients presented with a documented atrial arrhythmia. There were no significant differences in clinical outcomes among the devices. Transesophageal echocardiography follow-up revealed higher closure rates with GSO (92.6%) and BioSTAR (93.7%) compared with HELEX (74.2%; P = 0.031 and P = 0.034, respectively) and APO (76.4%; P = 0.036 and P = 0.041, respectively). The GSO and BioSTAR showed better closure rates than HELEX and APO at 4 months. PFO closure is a safe procedure with a low rate of clinical events at follow-up.
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