Results of intracoronary stem cell therapy after acute myocardial infarction.

To assess the effect of autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction in a rigorous double-blind, randomized, placebo-controlled trial. Patients with reperfusion >6 hours after symptom onset were randomly assigned in a 2:1 ratio to receive intracoronary BMC or placebo therapy 5 to 7 days after symptom onset. The patients were stratified according to age, acute myocardial infarction localization, and left ventricular (LV) function. Rigorous double-blinding was ensured using autologous erythrocytes for the placebo preparation that was visually indistinguishable from the active treatment. Serial cardiac magnetic resonance imaging studies were performed before study therapy and after 1, 3, and 6 months. The primary end point was the difference in the LV ejection fraction from baseline to 6 months. The secondary end points included changes in the LV end-diastolic and end-systolic volume indexes and infarct size. A total of 42 patients were enrolled (29 in the BMC group and 13 in the placebo group) in the integrated pilot phase. A mean of 381 x 10(6) mononuclear BMCs were administered. The baseline clinical and cardiac magnetic resonance imaging parameters did not differ. Compared to baseline, the difference in LV ejection fraction for the placebo group versus BMC group was 1.7 +/- 6.4% versus -0.9 +/- 5.5% at 1 month, 3.1 +/- 6.0% versus 1.9 +/- 4.3% at 3 months, and 5.7 +/- 8.4% versus 1.8 +/- 5.3% at 6 months (primary end point; not significant). No difference was found in the secondary end points between the 2 groups, including changes in infarct size or LV end-diastolic and end-systolic volume indexes. In conclusion, in this rigorous double-blind, randomized, placebo-controlled trial, we did not observe an evidence for a positive effect for intracoronary BMC versus placebo therapy with respect to LV ejection fraction, LV volume indexes, or infarct size.

Diagnostic performance of magnetic resonance first pass perfusion imaging is equally potent in female compared to male patients with coronary artery disease.

BACKGROUND: Noninvasive diagnosis of coronary artery disease (CAD) in women is crucial because of a lower prevalence of CAD in premenopausal women, different cardiac risk profile and pattern of CAD, lower exercise tolerance and more atypical symptoms compared to men. Therefore, we tested the diagnostic power of cardiac magnetic resonance first pass perfusion imaging (CMR-FPPI) for the diagnosis of significant coronary stenoses in females versus males. METHODS AND RESULTS: 256 consecutive patients, 77 females and 179 males with atypical or typical chest pain and intermediate risk of CAD were studied by coronary angiography and CMR-FPPI (1.5T Intera CV). A three-slice, short-axis perfusion scan with a saturation prepulse was performed during infusion of adenosine and at rest followed by late enhancement imaging for myocardial scar. Gadolinium-DTPA was administered at 0.1 mmol/kg body weight. Perfusion images were visually analysed, coronary stenoses by quantitative coronary angiography. Sensitivity, specificity and accuracy of CMR-FPPI for detection of a significant coronary artery stenosis (> or = 50% luminal narrowing) in the entire group were 91.3, 81.7 and 88.6%, the corresponding values for females were 90.9, 90.6 and 90.8% and for males 91.4, 74.4 and 87.7%, and in the subgroup of females with suspected primary CAD 83.3, 96.0 and 93.6%, and for suspected progression 92.1, 71.4 and 88.9%. CONCLUSION: Diagnostic accuracy of CMR-FPPI is very high in women with intermediate risk of CAD and comparable or in part superior to results in males. With the advantage of the absence of radiation exposure and high spatial and temporal resolution, CMR-FPPI has the potential to become the preferred imaging test to select women for coronary angiography.

Catheter-based delivery of fluid paclitaxel for prevention of restenosis in native coronary artery lesions after stent implantation.

BACKGROUND: Stents eluting antiproliferative drugs reduce the incidence of restenosis but delay healing of the vascular wall. We assessed the safety and efficacy of catheter-based local delivery of fluid paclitaxel in patients with coronary de novo stenoses after implantation of a bare metal stent. METHODS AND RESULTS: We conducted a prospective, randomized trial comparing the local delivery of fluid paclitaxel after bare metal stent implantation (group I) with the implantation of a bare metal stent (group II) and the implantation of a paclitaxel-eluting stent (group III) in 204 patients. The primary end point was in-stent late lumen loss. Secondary end points included binary restenosis rate >50%, minimal lumen diameter, diameter stenosis, and a composite clinical end point (major adverse cardiac events and revascularization of the target lesion) 6 months after intervention. At 6 months, angiography showed an in-stent late lumen loss of 0.61+/-0.44 mm in group I versus 0.99+/-0.72 mm in group II (I versus II, P=0.0006) and 0.44+/-0.48 mm in group III (noninferiority of I versus III, P=0.023). The 1-sided 95% CI for the true difference of the means of in-stent late lumen loss in groups I and III was -infinity to 0.3174188. The cumulative overall rate of major cardiac events was 13.4% in group I, 26.8% in group II, and 14.9% in group III. Target lesion revascularization rate was 13.4% (group I), 22.1% (group II), and 13.4% (group III). CONCLUSIONS: Additional antiproliferative treatment of de novo lesions in native coronary arteries with catheter-based delivery of fluid paclitaxel after bare metal stenting was safe and significantly reduced neointimal proliferation, restenosis, and clinical events compared with bare metal stent implantation alone.

Angiographic results of the cobalt chromium Vision and Mini-Vision stents.

BACKGROUND: Drug-eluting stents (DES) have been shown to reduce repeat revascularizations compared with their bare-metal stent (BMS) platforms. Modern BMS may be associated with better angiographic results compared with the older BMS platforms. In the Basel Stent Kosten Effektivitats Trial (BASKET), target vessel revascularization after six months was nonsignificantly different between DES and BMS with clinical follow-up. OBJECTIVES: To evaluate angiographic results of the cobalt chromium Vision and Mini-Vision stents (Abbott Vascular, USA). METHODS: A total of 247 consecutive patients with 293 de novo lesions in native coronary arteries were treated with cobalt chromium Vision (n=184; stent diameter 2.75 mm to 4.0 mm) or Mini-Vision stents (n=109; stent diameter 2.0 mm to 2.5 mm), and scheduled for six months of angiographic follow-up. The primary end point was in-stent late loss after six months. RESULTS: Acute coronary syndromes were present in 83.4% (n=206) of patients. The preinterventional reference diameter of Vision stents was 2.70+/-0.34 mm and for Mini-Vision stents, it was 2.13+/-0.27 mm (P<0.001). Clinical and angiographic follow-up was 98.0% and 51.2%, respectively. In the Vision group, in-stent late loss was 0.64+/-0.67 mm and the binary restenosis rate was 17.9%. In the Mini-Vision group, in-stent late loss was 0.82+/-0.71 mm and the restenosis rate was 45.4%. No difference in occurrence of restenosis within the segments proximal or distal to the stent was observed. The restenotic pattern was predominantly focal with a short length of 7.9+/-4.4 mm. CONCLUSIONS: The use of the cobalt chromium Vision stent for the treatment of de novo lesions was associated with a low late loss and binary angiographic restenosis rate.

Impact of percutaneous device implantation for closure of patent foramen ovale on valve insufficiencies.

BACKGROUND: In patients with percutaneous device implantation for closure of patent foramen ovale (PFO), a 10% incidence of new or worsened aortic regurgitation within 12 months has been reported with echocardiography. Cardiac magnetic resonance imaging is a powerful noninvasive tool to quantify volume and fraction of valve insufficiencies. We studied the acute and long-term impact of percutaneous device implantation for PFO closure on valve insufficiencies in cardiac magnetic resonance imaging. METHODS AND RESULTS: Sequential cardiac magnetic resonance imaging studies were performed in 102 patients with cryptogenic ischemic events. Cardiac magnetic resonance imaging was performed before PFO closure, the day after device implantation, and at 12 months of follow-up. There was no difference in volumetric and hemodynamic parameters before PFO closure compared with 12 months of follow-up. With a cutoff for relevant regurgitation fraction of 5%, there were no statistically significant differences in regurgitation fraction of the semilunar and atrioventricular valves. The median fraction of aortic valve insufficiency was 3.9% (interquartile range [IQR] 2.0% to 5.1%) before PFO closure, 5.4% (IQR 4.1% to 5.9%) after device implantation, and 4.3% (IQR 3.3% to 6.0%) at 12 months of follow-up. The size and type of the occluder had no impact on aortic valve insufficiency. Median regurgitation fraction for the pulmonary valve was 3.6% (IQR 2.4% to 6.7%) before intervention, 7.3% (IQR 5.1% to 8.2%) after occluder implantation and 5.8% (IQR 4.8% to 7.4%) at 12 months of follow-up. Values for the mitral valve were 3.1% (IQR 1.4% to 6.0%), 5.5% (IQR 3.5% to 7.3%), and 3.8% (IQR 1.5% to 7.9%) and for the tricuspid valve were 5.4% (IQR 0.1% to 8.8%), 5.8% (IQR 1.4% to 9.2%), and 6.0% (IQR 1.1% to 8.4%), respectively. CONCLUSIONS: Percutaneous PFO closure with device implantation has no impact on valve insufficiencies as determined by cardiac magnetic resonance imaging.

Angiographic results of a Tacrolimus-eluting stent in acute coronary syndrome lesions.

BACKGROUND: The Janus stent releases Tacrolimus from reservoirs located at the abluminal stent surface without any polymer. In stable coronary lesions the stent did not show relevant antiproliferative effects. Since Tacrolimus provides antiproliferative and antiinflammatory properties, we sought to investigate the efficacy of the Tacrolimus eluting Janus stent in acute coronary syndrome lesions with a more pronounced inflammatory cell reaction compared to stable coronary artery lesions. METHODS: Patients with acute coronary syndrome (STEMI or NSTEMI) undergoing cardiac catheterization and stent implantation were enrolled in this prospective registry. Primary outcome measure was in-stent late lumen loss at 6 months. There were two pre-specified subgroups based on presence or absence of high-pressure post-dilation (HPPD) with a balloon >or= 0.25 mm larger than the delivery balloon. RESULTS: Sixty patients were enrolled. In 34 patients HPPD was performed. Reference diameter was 2.85+/-0.57 mm. Stented length was 30.8+/-23.8 mm in HPPD and 19.7+/-7.3 mm in non-HPPD group. For the total population in-stent late loss was 0.92+/-0.80 mm and binary restenosis rate 32.6%. Late loss (1.09+/-0.74 mm Vs. 0.64+/-0.83 mm) and binary restenosis rate (37.0% Vs. 25.0%) were higher in the HPPD subgroup compared to lesions in non-HPPD. The angiographic evidence of thrombus was associated with a higher late loss. Restenotic pattern was occlusive in 40%, diffuse in 33% and focal in 27%. CONCLUSION: The use of the Tacrolimus eluting Janus stent in acute coronary syndrome lesions was associated with a high late lumen loss, a high angiographic restenosis rate and a mainly occlusive or diffuse pattern of restenosis.

Carbon-coated stents in patients with acute coronary syndromes.

BACKGROUND: For patients with ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI), rapid restoration of coronary blood flow is the primary therapeutic goal. Because of the acute nature of this clinical presentation, bleeding risks may not be adequately evaluated, limiting the use of drug-eluting stents, since premature discontinuation of antiplatelet therapy strongly predicts stent thrombosis. We evaluated angiographic and clinical results of non-drug-eluting carbon-coated stents. METHODS: In this prospective observational study, angiographic and clinical 6-mo results of a carbon-coated stent for treatment of acute lesions in native coronary arteries were evaluated. Angiographic main outcome measures included in-stent late loss and binary restenosis rate. Major adverse cardiac events (MACEs) were defined as any death, Q-wave myocardial infarction (MI), and target lesion revascularization. RESULTS: We included 320 patients with STEMI (n = 205) or NSTEMI (n = 115) with 360 lesions. Reference vessel diameter was 2.93 +/- 0.53 mm and stented length 22.7 +/- 13.8 mm. Angiographic follow-up was available in 220 of 360 lesions (61%). In-stent late loss was 0.69 +/- 0.75 mm, with a binary restenosis rate of 19.1%. For the total segment late loss was 0.74 +/- 0.77 mm and binary restenosis rate 21.4%. Clinical follow-up for 97.4% of discharged patients was available. Hierarchical MACEs were death in 14 patients (4.4%), Q-wave MI in 3 patients (0.9%), and target lesion revascularization in 39 patients (12.2%). CONCLUSION: In this prospective, observational study, the use of a carbon-coated stent for treatment of lesions in patients with STEMI or NSTEMI was associated with a low late loss, translating into a low binary angiographic restenosis rate within a 6-mo follow-up.

Characterization of patients with acute chest pain using cardiac magnetic resonance imaging.

AIMS: The purpose of this study was to evaluate whether CMRI provides characteristic findings in patients with acute chest pain suffering from ST-elevation-myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), acute myocarditis or Tako-tsubo cardiomyopathy. PATIENTS AND METHODS: 230 consecutive patients with acute chest pain underwent cardiac catheterization followed by CMRI within median 5 days. Patients were classified to suffer from STEMI (n = 102), NSTEMI (n = 89), acute myocarditis (n = 27), or Tako-tsubo cardiomyopathy (n = 12) on the synopsis of all clinical data. Wall motion abnormalities, late enhancement (LE), persistent microvascular obstruction as well ventricular volumes and functions were assessed by CMRI. RESULTS: Right and left ventricular volumes were significantly different between the groups and values were highest in patients with acute myocarditis. Wall motion abnormalities were observed in 100% of STEMI, 75% of NSTEMI, 67% of acute myocarditis and 100% of Tako-tsubo patients. There was a characteristic pattern of abnormal wall motion focused on midventricular-apical segments in patients with Tako-tsubo cardiomyopathy, depending on the culprit vessel in patients with STEMI/NSTEMI and with a random distribution in patients with acute myocarditis. LE was mainly subendocardial or transmural in patients with STEMI (93.2%) or NSTEMI (62.9%). LE was diffuse, intramural or subepicardial in patients with acute myocarditis. No LE was observed in patients with Tako-tsubo cardiomyopathy. Persistent microvascular obstruction was only visualized in patients with STEMI (33%) or NSTEMI (6%). CONCLUSIONS: Cardiac magnetic resonance imaging provides characteristic patterns of LE, persistent microvascular obstruction and wall motion abnormalities that allow a differentiation between patients with acute chest pain from coronary and non-coronary origin.

Impact of pioglitazone on coronary endothelial function in non-diabetic patients with coronary artery disease.

OBJECTIVE: Pioglitazone has been shown to exert multiple antiatherosclerotic actions independent from its glycemic effects. We studied the hypothesis that pioglitazone improves coronary endothelial dysfunction in non-diabetic patients with coronary artery disease (CAD) in a randomized, placebo-controlled, double-blind trial. METHODS: Fifty non-diabetic patients with CAD were randomized to 6 months treatment with pioglitazone 30 mg daily or placebo. Coronary endothelial function was tested at baseline and after 6 months with intracoronary infusion of adenosine, acetylcholine (0.072; 0.72; 7.2, and 36 microg/min), glyceroltrinitrate, and cold pressor test (CPT). The primary endpoint was the mean effect of treatment compared with placebo on acetylcholine-induced coronary vascular response for all acetylcholine dosages, based on percent change in luminal area measured by quantitative coronary angiography. RESULTS: There was no difference in baseline coronary endothelial function. The primary endpoint was significantly different between the groups with a 1.8% +/- 2.0% increase in luminal area between baseline and follow-up with pioglitazone and a 7.6% +/- 2.4% decrease in the placebo group (P < 0.008). At follow-up, there was a trend for a difference in CPT (P = 0.057). No difference was observed regarding intracoronary glyceroltrinitrate or adenosine. CONCLUSIONS: Pioglitazone treatment in non-diabetic patients with CAD was associated with a significantly better coronary endothelial function compared to placebo.

Intracoronary application of abciximab in patients with ST-elevation myocardial infarction.

AIMS: Abciximab provides dose-dependent antiplatelet and anti-inflammatory properties. No specifically designed prospective studies have addressed the role of intracoronary bolus administration of abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: In a prospective observational study 633 STEMI patients were enrolled. After coronary angiography the filtered abciximab bolus with a concentration of 2,000 microg/mL was administered intracoronary by manual injection, followed by an intravenous infusion for 12 hours. Primary outcome measure was the cumulative rate of major adverse cardiac events (MACE) at 30 days defined as death, myocardial infarction or urgent target vessel revascularisation. Bleeding events were classified according to TIMI criteria. Patients with failed thrombolysis, cardiopulmonary resuscitation, cardiogenic shock, advanced age, or renal failure were assigned to group II; patients without those criteria were assigned to group I and compared to previous populations with intravenous bolus administration. There were no safety issues. In group I MACE occurred in 3.6% (N=16/451), major TIMI bleed in 2.0%. MACE and bleeding events were significantly less frequent in group I compared to group II (both p<0.0001). Significant predictors for MACE in multivariate statistics were assignment to group II (OR 11.69; 95%-CI 6.26-21.83; p<0.0001), post PCI TIMI 0-2 flow (OR 3.87; 95%-CI 2.02-7.44; p<0.0001) and female gender (OR 2.05; 95%-CI 1.15-3.65, p=0.014). CONCLUSIONS: The intracoronary administration of the abciximab bolus during PCI in STEMI patients is safe and associated with a low rate of MACE at 30 days.

Magnetic resonance imaging to assess acute changes in atrial and ventricular parameters after transcatheter closure of atrial septal defects.

PURPOSE: To evaluate acute changes in atrial and ventricular parameters by the use of cardiac magnetic resonance imaging (MRI) in patients with percutaneous transcatheter atrial septal defects (ASD) closure. MATERIALS AND METHODS: The study included 14 patients (six males and eight females, 45 +/- 18 years) with congenital ASD. Cardiac MRI (1.5T Philips Intera CV) was performed before and within 24 hours after transcatheter ASD closure. Right atrial (RA) and left atrial (LA) dimensions, as well as right (RV) and left (LV) ventricular end-diastolic (ED) volumes were determined. Atrial size was assessed by planimetry of the maximum RA and LA areas in a standard four-chamber view, and ventricular volumes were calculated according to a modified Simpson's rule in short-axis views. RESULTS: The mean RA decreased significantly from 27.6 +/- 6.4 cm(2) before closure to 24.4 +/- 5.6 cm(2) after the procedure (P = 0.0018), whereas the LA area did not change (24.1 +/- 4.7 cm(2) vs. 23.8 +/- 5.2 cm(2), P = 0.76). The RV volumes, volume index, and ejection fraction (EF) decreased significantly from 229 +/- 64 mL to 181 +/- 43 mL (P < 0.001, average reduction = 19% +/- 15%), from 126.0 +/- 37.2 mL/m(2) to 96.6 +/- 28.6 mL/m(2) (P < 0.0001) and from 64 +/- 5% to 58% +/- 7% (P = 0.01), respectively. The LV volumes and volume index remained unchanged (114 +/- 25 mL vs. 118 +/- 22 mL, P = 0.18, 63.5 +/- 13.5 mL/m(2) vs. 63.0 +/- 17.4 mL/m(2), P = 0.83). Left-right shunting decreased from 40% +/- 15% to 9% +/- 15% (P < 0.001). CONCLUSION: Cardiac MRI can reveal detailed information on acute changes in shunt fraction and ventricular dimensions after ASD closure. ASD closure by percutaneous transcatheter device implantation results within 24 hours in a significant reduction of shunt fraction, RA and RV sizes, and RV function, whereas LA and LV dimensions remain unchanged.

Assessment of myocardial perfusion for detection of coronary artery stenoses by steady-state, free-precession magnetic resonance first-pass imaging.

OBJECTIVE: To evaluate the diagnostic impact of magnetic resonance imaging (MRI) first-pass perfusion using steady-state, free-precession (SSFP) sequences with parallel imaging (SENSE) for detection of coronary stenoses. DESIGN: Prospective observational study. SETTING: University hospital, cardiac MRI and catheterisation laboratories. PATIENTS AND METHODS: 228 patients were examined with coronary angiography and MRI (1.5 T Intera CV). A three-slice, short-axis SSFP perfusion scan with a saturation prepulse was performed during infusion of adenosine and at rest followed by myocardial scar (late enhancement) imaging. Gadolinium-DTPA was given at 0.1 mmol/kg body weight. Perfusion images were visually assessed. Analysis for myocardial hypoperfusion was done according to patient group and according to vessel. RESULTS: Sensitivity, specificity and accuracy of MRI first-pass perfusion for detection of a coronary artery stenosis (>50% luminal narrowing) in the total patient group were 93.0%, 85.7%, 91.2% and for a significant lesion (>70% luminal narrowing) 96.1%, 72.0%, 88.2%, respectively. Based on 536 coronary artery territories without myocardial scar, the sensitivity of MRI perfusion analysis for detection of a significant lesion was for the left anterior descending artery 91.4%, for the circumflex artery 81.6% and for the right coronary artery 65.1% (p<0.001). CONCLUSIONS: MRI first-pass perfusion analysis using an SSFP sequence with three myocardial slices was a highly accurate diagnostic method for detection of coronary artery stenoses. This MRI technique can be included in daily practice and has the potential to guide the indication for invasive coronary angiography.

Myocardial perfusion reserve in cardiovascular magnetic resonance: Correlation to coronary microvascular dysfunction.

The present study examined the association of myocardial perfusion reserve index (MPRI) in cardiovascular magnetic resonance (CMR) with coronary microvascular dysfunction (CMD) and serum levels of markers of inflammation or endothelial activation. Twelve patients with typical angina pectoris without coronary artery disease were enrolled in this study, and CMR perfusion was analyzed using a steady-state-free-precession sequence with 3 short axis slices per heartbeat during first pass of 0.025 mmol Gadolinium-DTPA/kg body weight. The upslope of myocardial signal intensity curves was used to calculate MPRI. CMD was assessed by intracoronary Doppler flow measurement and biplane angiography. Both MPRI and CMD were assessed during endothelium-independent stimulation with intravenous adenosine and during endothelium-dependent stimulation with intracoronary infusion of acetylcholine. Serum values of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and C-reactive protein (CRP) were measured. Impaired MPRI correlated significantly with a decrease in coronary blood flow reserve after both endothelium-dependent (p = 0.033) and endothelium-independent (p = 0.022) stimulation. Serum levels above the median of all normal ranged biomarkers sCD40L, TNF-alpha, IL-6, sICAM-1 and CRP were associated with an impaired MPRI for stimulation with adenosine as well as acetylcholine. In multivariable analyses, sCD40L (p < 0.001) and TNF-alpha (p = 0.011) were significantly associated with a decrease in MPRI on adenosine, as were TNF-alpha (p = 0.016) and sICAM-1 (p = 0.022) for a decrease in MPRI on acetylcholine. MPRI on adenosine significantly correlated with MPRI on acetylcholine (p < 0.001). Therefore, the present study demonstrates safety and feasibility of an intracoronary infusion of acetylcholine during CMR perfusion analysis, thus allowing direct assessment of endothelial dependent vasomotor function at the myocardial level by CMR. Furthermore, we show that an impaired myocardial perfusion reserved in CMR is associated with established biomarkers of early atherosclerosis and significantly correlated with CMD. CMR combined with adenosine could be proposed as a non-invasive tool to evaluate CMD.

Cardiac magnetic resonance imaging and transesophageal echocardiography in patients with transcatheter closure of patent foramen ovale.

OBJECTIVES: We studied the value of cardiac magnetic resonance imaging (CMRI) before and after closure of patent foramen ovale (PFO) in patients with cryptogenic ischemic events. BACKGROUND: Cardiac magnetic resonance imaging is a powerful noninvasive tool for detailed assessment of cardiac anatomy and function. The relevance of CMRI compared with transesophageal echocardiography (TEE) in patients undergoing transcatheter PFO closure has not been evaluated so far. METHODS: Contrast-enhanced CMRI and TEE were performed in 75 patients before and after PFO closure. Twelve months after PFO closure, both imaging techniques were repeated in 61 patients with contrast application. To determine provokable atrial right-to-left shunting in CMRI, we applied a contrast-enhanced perfusion imaging technique. Detection of atrial septal aneurysm (ASA) was achieved by means of a high-resolution cine imaging technique. RESULTS: Before PFO closure, ASA was seen with CMRI in 28 of 75 cases (37.3%), compared with 47 of 75 (62.7%) cases using TEE. There were a total of 211 CMRI studies with a corresponding TEE performed in 75 patients. No shunt was present in 107 of 211 studies with both techniques. Contrast-enhanced right-to-left shunting was detected by CMRI in 48 of 72 (66.6%) cases with moderate or severe shunts seen with TEE, but only in 6 of 32 (18.8%) studies with mild shunts with TEE. Anomalous venous returns were excluded in all patients. In two patients, coronary anomalies were seen. CONCLUSIONS: The present CMRI technique is inferior to TEE in detection of contrast-enhanced right-to-left shunting and identification of ASA.

Intracoronary beta-brachytherapy using a rhenium-188 filled balloon catheter in restenotic lesions of native coronary arteries and venous bypass grafts.

PURPOSE: We have previously demonstrated the efficacy of intracoronary beta-brachytherapy using a liquid (188)Re-filled balloon in a randomised trial including de novo lesions. Percutaneous coronary interventions in restenotic lesions and in stenoses of venous bypass grafts are characterised by a high recurrence rate for restenosis and re-interventions. Against this background, we wanted to assess the impact of intracoronary beta-brachytherapy using a liquid (188)Re-filled balloon in restenotic lesions in native coronary arteries and venous bypass grafts. METHODS: In 243 patients, beta-brachytherapy with 22.5 Gy was applied at a tissue depth of 0.5 mm. Patients were followed up angiographically after 6 months and clinically for 12 months. The primary clinical endpoint was the incidence of MACE (death, myocardial infarction, target vessel revascularisation). Secondary angiographic endpoints were late loss and binary restenosis rate in the total segment. RESULTS: All irradiation procedures were successfully performed. A total of 222 lesions were in native coronary arteries; 21 were bypass lesions. Mean irradiation length was 41.6+/-17.3 mm (range 20-150 mm) in native coronary arteries and 48.1+/-33.9 mm (range 30-180 mm) in bypass lesions; the reference diameter was 2.57+/-0.52 mm and 2.83+/-0.76 mm, respectively. There was no vessel thrombosis during antiplatelet therapy. Angiographic/clinical follow-up rate was 84%/100%. MACE rate was 17.6% in the native coronary artery group and 38.1% in the CABG group (p<0.03). Binary restenosis rate was 22.5% and 55.6% (p<0.01), and late loss was 0.38+/-0.72 mm and 1.33+/-1.11 mm (p<0.001), respectively. CONCLUSIONS: We conclude that intracoronary beta-brachytherapy with a liquid (188)Re-filled balloon using 22.5 Gy at a tissue depth of 0.5 mm in restenotic lesions is safe. It is associated with a low binary restenosis rate, resulting in a low occurrence rate of MACE within 12 months in restenotic lesions in native coronary arteries but not in vein grafts.

Repeat intracoronary beta-brachytherapy using a rhenium-188-filled balloon catheter for recurrent restenosis in patients who failed intracoronary radiation therapy.

BACKGROUND: Conventional percutaneous coronary intervention (PCI) in restenotic lesions after brachytherapy failure is associated with a high recurrence rate of restenoses and revascularizations. Intracoronary brachytherapy using a liquid rhenium-188-filled balloon in de novo or restenotic lesions safely and effectively reduced restenosis rates. We report clinical and angiographic data regarding the safety and efficacy of rhenium-188 brachytherapy in restenoses after brachytherapy failure. METHODS: Fourteen patients with restenosis after brachytherapy failure received rhenium-188 beta-brachytherapy. Follow-up was performed angiographically after 6 months and clinically after 12 months. Primary clinical endpoint was the incidence of major adverse cardiac events (MACE) defined as any death, myocardial infarction or repeat revascularization in the target vessel within 12 months. Secondary angiographic endpoints were the binary restenosis rate and late loss in the total segment including edge effects at 6 months. RESULTS: The prescribed dose of 22.5 Gy (n=12) or 30 Gy (n=2) was successfully delivered in all patients. In two lesions, a bare-metal stent was implanted. The mean length of the irradiated segment was 40.0+/-15.7 mm. The mean diameter of the irradiation balloon was 2.96+/-0.37 mm. Angiographic follow-up was done in 13 of 14 patients. There was no edge stenosis or coronary aneurysm. Within the total segment, late loss was 0.39+/-0.64 mm and late loss index was 0.18+/-0.40 with a binary restenosis rate of 23%. Twelve months' clinical follow-up was available in all patients, which showed a MACE rate of 7% due to one target lesion revascularization (TLR). CONCLUSIONS: Intracoronary beta-brachytherapy with a liquid rhenium-188-filled balloon in restenoses after intracoronary radiation therapy failure including 12 months combined antiplatelet therapy is safe with respect to vessel thrombosis, late coronary occlusion or aneurysm formation. With limited use of stenting, angiographic and clinical follow-up for repeat brachytherapy were favorable and it is associated with low restenosis and target vessel revascularization rate.

Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic resonance in dilated cardiomyopathy.

BACKGROUND: In some patients suffering from dilated cardiomyopathy (DCM) magnetic resonance imaging (MRI) shows late gadolinium enhancement with variable distribution. Myocardial biopsies in DCM reveal a chronic myocardial inflammatory process in almost 50% and myocardial persistence of adenoviral or enteroviral genome in about 15% of the patients. AIMS: We prospectively investigated whether the pattern of late gadolinium enhancement correlates with myocardial biopsy findings. METHODS AND RESULTS: 42 patients with DCM and 42 control subjects underwent contrast MRI. In the DCM group, endomyocardial biopsies were performed and evaluated for inflammation and viral genome. None of the control subjects showed late gadolinium enhancement whereas in 29 DCM patients (69%) gadolinium enhancement was detectable (p<0.001). 21 of the DCM patients (50%) showed midwall septal enhancement, 7 patients (17%) showed a patchy distribution of hyperenhancement and 1 patient (2%) showed enhancement typical for ischemic heart disease. In myocardial biopsy analysis, 2 patients (5%) showed persistence of viral genome, 18 patients (43%) showed inflammation and in 22 patients (52%) neither virus nor inflammation was detected. The pattern of late gadolinium enhancement and myocardial biopsy findings were not significantly correlated (p = 0.854). CONCLUSION: MRI as a non-invasive technique cannot replace myocardial biopsy for the differential diagnosis of DCM.

Pioglitazone reduces neointima volume after coronary stent implantation: a randomized, placebo-controlled, double-blind trial in nondiabetic patients.

BACKGROUND: Restenosis requiring reintervention limits the long-term success after coronary stent implantation. Thiazolidinediones, like pioglitazone or rosiglitazone, are oral antidiabetic drugs with additional antirestenotic properties. In a randomized, placebo-controlled, double-blind trial, we examined the effect of 6-month pioglitazone therapy on neointima volume after coronary stenting in nondiabetic coronary artery disease patients. METHODS AND RESULTS: Fifty nondiabetic patients after coronary stent implantation were randomly assigned to pioglitazone (30 mg daily; pio) or placebo (control) treatment in addition to standard therapy, and neointima volume was assessed by intravascular ultrasound at the 6-month follow-up. Both groups were comparable with regard to baseline characteristics, angiographic lesion morphology, target vessel, and length of the stented segment. In addition, there were no statistical differences in minimal lumen diameter before and after intervention, as well as reference diameter after stent implantation. In this study population of nondiabetic patients, pio treatment did not significantly change fasting blood glucose, fasting insulin, or glycosylated hemoglobin levels, as well as lipid parameters. In contrast, pio treatment significantly reduced neointima volume within the stented segment, with 2.3+/-1.1 mm3/mm in the pio group versus 3.1+/-1.6 mm3/mm in controls (P=0.04). Total plaque volume (adventitia-lumen area) was significantly lower at follow-up in the pio group (11.2+/-3.2 mm3/mm) compared with controls (13.2+/-4.2 mm3/mm; P=0.04). Moreover, the binary restenosis rate was 3.4% in the pio group versus 32.3% in controls (P<0.01). CONCLUSIONS: Thus, 6-month treatment with pio significantly reduced neointima volume after coronary stent implantation in nondiabetic patients. These data bolster the hypothesis that antidiabetic thiazolidinediones, in addition to their metabolic effects, exhibit direct antirestenotic effects in the vasculature.

Intracoronary beta-irradiation with a rhenium-188-filled balloon catheter: a randomized trial in patients with de novo and restenotic lesions.

BACKGROUND: Restenosis requiring reintervention is the main limitation of coronary angioplasty. Intracoronary irradiation reduces neointimal proliferation. We studied the efficacy of a self-centering liquid rhenium-188-filled balloon catheter for coronary beta-brachytherapy. METHODS AND RESULTS: After successful coronary angioplasty with or without stenting, 225 patients (71% de novo lesions) were randomly assigned to receive 22.5 Gy intravascular beta-irradiation in 0.5-mm tissue depth (n=113) or to receive no additional intervention (n=112). Clinical and procedural data did not differ between the groups except a higher rate of stenting in the control group (63%) compared with the rhenium-188 group (45%, P<0.02). After 6 months of follow-up, late loss was significantly lower in the irradiated group compared with the control group, both of the target lesion (0.11+/-0.54 versus 0.69+/-0.81 mm, P<0.0001) and of the total segment (0.22+/-0.67 versus 0.70+/-0.82 mm, P<0.0001). This was also evident in the subgroup of patients with de novo lesions and independent from stenting. Binary restenosis rates were significantly lower at the target lesion (6.3% versus 27.5%, P<0.0001) and of the total segment (12.6% versus 28.6%, P<0.007) after rhenium-188 brachytherapy compared with the control group. Target vessel revascularization rate was significantly lower in the rhenium-188 (6.3%) compared with the control group (19.8%, P=0.006). CONCLUSIONS: Intracoronary beta-brachytherapy with a rhenium-188 liquid-filled balloon is safe and efficiently reduces restenosis and revascularization rates after coronary angioplasty.

No effect of highly dosed nitric oxide donor molsidomine on the angiographic restenosis rate after percutaneous coronary angioplasty: a randomized, placebo controlled, double-blind trial.

BACKGROUND: Nitric oxide (NO) counteracts several mechanisms involved in the restenotic process after coronary angioplasty. NO mediates an antiproliferative effect on smooth muscle cells, inhibition of leukocyte-vessel wall interactions, and platelet aggregation and adhesion. Because these effects are mainly dose dependent, NO-releasing drugs have to be applied at a high dose to have an effect on restenotic mechanisms. OBJECTIVES: To study the effect of the NO donor molsidomine at a high dose of 8 mg tid on angiographic restenosis rate in a randomized, placebo controlled, double-blind trial. PATIENTS AND METHODS: One hundred and sixty-six patients with de novo stenosis were randomly assigned to molsidomine or placebo treatment for six months (83 patients each). The primary end point was the angiographic restenosis rate at six months. The secondary end points were major adverse cardiac events (MACE) including death, myocardial infarction and revascularization. Analyses were performed by intention to treat. RESULTS: There were no differences in clinical, procedural and angiographic data, including minimum lumen diameter and reference diameter. Provisional stenting was performed in 28% of patients receiving molsidomine and 25% of patients treated with placebo. All other patients were treated with standard balloon angioplasty. Reangiography rate was 89.3% (molsidomine 90 lesions, placebo 97 lesions). Restenosis rate (greater than 50% diameter stenosis) was not significantly different (molsidomine 25.6% and placebo 29.9%). Patients receiving molsidomine improved significantly more in their anginal class than patients receiving placebo (P<0.026). Occurrence of MACE did not significantly differ between both groups (molsidomine 26.8% and placebo 34.9%, P=0.26). CONCLUSION: Treatment with the NO donor molsidomine at a high dose of 8 mg tid for six months after coronary angioplasty has no effect on the angiographic restenosis rate. Due to the vasodilating effect of NO, the anginal status improves slightly more in patients receiving molsidomine.