Effect of pressure-controlled intermittent coronary sinus occlusion (PICSO) on myocardial ischaemia and reperfusion in a closed-chest porcine model.

AIMS: To investigate a pressure-controlled intermittent coronary sinus occlusion (PICSO) system in an ischaemia/reperfusion model. METHODS AND RESULTS: We randomly assigned 18 pigs subjected to 60 minutes ischaemia by left anterior descending (LAD) coronary artery balloon occlusion to PICSO (n=12, groups A and B) or to controls (n=6, group C). PICSO started 10 minutes before (group A), or 10 minutes after (group B) reperfusion and was maintained for 180 minutes. A continuous drop of distal LAD pressure was observed in group C. At 180 minutes of reperfusion, LAD diastolic pressure was significantly lower in group C compared to groups A and B (p=0.02). LAD mean pressure was significantly less than the systemic arterial mean pressure in group C (p=0.02), and the diastolic flow slope was flat, compared to groups A and B (p=0.03). IgG and IgM antibody deposition was significantly higher in ischaemic compared to non-ischaemic tissue in group C (p<0.05). Significantly more haemorrhagic lesions were seen in the ischaemic myocardium of group C, compared to groups A and B (p=0.002). The necrotic area differed non-significantly among groups. CONCLUSIONS: PICSO was safe and effective in improving coronary perfusion pressure and reducing antibody deposition consistent with reduced microvascular obstruction and ischaemia/reperfusion injury.

Cardiac shock wave therapy for chronic refractory angina pectoris. A prospective placebo-controlled randomized trial.

BACKGROUND: Cardiac shock wave therapy (CSWT) delivered to the myocardium increases capillary density and regional myocardial blood flow in animal experiments. In addition, nonenzymatic nitric oxide production and the upregulation of vascular growth factor's mRNA by CSWT have been described. The aim of the study was therefore to test its potential to relieve symptoms in patients with chronic stable angina pectoris. METHODS: Twenty-one patients (mean age 68.2 ± 8.3 years, 19 males) with chronic refractory angina pectoris and evidence of inducible myocardial ischemia during MIBI-SPECT imaging, were randomized into a treatment (n = 11) and a placebo arm (n = 10). The region of exercise-induced ischemia was treated with echocardiographic guidance during nine sessions over a period of 3 months. One session of CSWT consisted of 200 shots/spot (9--12 spots/session) with an energy intensity of 0.09 mJ/mm(2) . In the control group acoustic simulation was performed without energy application. Medication was kept unchanged during the whole treatment period. RESULTS: In the treatment group, symptoms improved in 9/11 patients, and the ischemic threshold, determined by cardiopulmonary exercise stress testing, increased from 80 ± 28 to 95 ± 28 W (P= 0.036). In the placebo arm, only 2/10 patients reported an improvement and the ischemic threshold remained unchanged (98 ± 23 to 107 ± 23 W; P= 0.141). The items "physical functioning" (P= 0.043), "general health perception" (P= 0.046), and "vitality" (P= 0.035) of the SF-36 questionnaire significantly improved in the treatment arm, whereas in the placebo arm, no significant change was noted. Neither arrhythmias, troponin rise nor complications were observed during treatment. CONCLUSIONS: This placebo controlled trial shows a significant improvement in symptoms, quality of life parameters and ischemic threshold during exercise in patients with chronic refractory angina pectoris treated with CSWT. Thus, CSWT represents a new option for the treatment of patients with refractory AP.

A prospective randomised comparison of titanium-nitride-oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome: the BASE-ACS trial.

AIMS: Titanium-nitride-oxide-coated bioactive stents (BAS) have demonstrated a favourable outcome when compared with paclitaxel-eluting stents in patients with acute myocardial infarction (MI). In a prospective randomised non-inferiority study design, we compared the safety and efficacy of BAS versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We randomised 827 patients with ACS (1:1) to either BAS (417) or EES (410). The primary endpoint was a composite of cardiac death, non-fatal MI or ischaemia-driven target lesion revascularisation (TLR) at 12-month follow-up. Analyses were performed by intention to treat. At 12-month follow-up, the primary composite endpoint occurred in 9.6% of patients in the BAS group and 9.0% of those in the EES group (HR [hazard ratio] 1.04, 95% CI [confidence interval] 0.81-1.32, p=0.81, p for non-inferiority =0.001). Non-fatal MI was significantly less frequent in the BAS as compared with the EES group (2.2% vs. 5.9%, p=0.007). However, the individual rates of cardiac death and ischaemia-driven TLR were similar between the two groups (1.9% vs. 1.0%, p=0.39, and 6.5% vs. 4.9%, p=0.37, respectively). CONCLUSIONS: In patients presenting with ACS, BAS achieved a clinical outcome that was non-inferior to EES at 12-month follow-up.

Evaluation of multimeric tyrosine-O-sulfate as a cytoprotectant in an in vivo model of acute myocardial infarction in pigs.

OBJECTIVES: Intracoronary administration of glycosaminoglycan analogs, including the complement inhibitor dextran sulfate, attenuates myocardial ischemia/reperfusion injury (I/R injury). However, dextran sulfate has a distinct anticoagulatory effect, possibly limiting its use in specific situations in vivo. We therefore developed multimeric tyrosine sulfate (sTyr-PAA), a novel, minimally anticoagulatory, fully synthetic non-carbohydrate-containing polyacrylamide conjugate, for in vivo testing in an acute closed-chest porcine model of acute myocardial infarction. METHODS: Following balloon occlusion of the left anterior descending artery just after the first diagonal branch (60-minute ischemia), sTyr-PAA (approx. 10 mg/kg bodyweight, fraction with strongest complement-inhibitory and minimal anticoagulatory properties, n = 11) or phosphate-buffered saline (controls, n = 9) was administered intracoronarily into ischemic myocardium prior to 120 min of reperfusion. RESULTS: sTyr-PAA significantly reduced infarct size (from 61.0 ± 12.0% of the ischemic area at risk to 39.4 ± 17.0%), plasma creatine kinase, local complement deposition and tissue factor upregulation, without affecting systemic coagulation. Protection was associated with significantly reduced myocardial neutrophil extravasation and translated into a significant improvement of ejection fraction and left ventricular enddiastolic pressure. CONCLUSIONS: sTyr-PAA protected significantly against myocardial I/R injury without substantially affecting systemic coagulation. Local intravascular sTyr-PAA administration may prove advantageous in situations where bleeding complications are likely or are to be avoided at all costs.

Clinical long-term outcome after implantation of titanium nitride-oxide coated stents compared with paclitaxel- or sirolimus-eluting stents: propensity-score matched analysis.

AIMS: We performed a propensity score matched analysis to explore whether TiNOX stents are superior to paclitaxel- (PES) and sirolimus-eluting stents (SES) in routine clinical practice. METHODS AND RESULTS: A total of 1,607 patients undergoing implantation of SES, PES or TiNOX stents were prospectively entered into a stent registry and followed up for three years. Using propensity score matching, we compared clinical outcome among 319 pairs of patients treated with TiNOX stents or SES and 337 pairs of patients treated with TiNOX stents or PES. The primary outcome MACE, a composite of death, myocardial infarction, and target vessel revascularisation occurred in 20% of patients with TiNOX stents, 19% of patients with SES and 23% of patients with PES at 3-years. The hazard ratio was 1.00 comparing TiNOX stents with SES (95% CI 0.69-1.45, p=1.00), and 0.95 comparing TiNOX stents with PES (95% CI 0.66-1.36, p=0.78). CONCLUSION: We did not find evidence to suggest superiority of TiNOX stents over SES or PES. In view of similar clinical outcomes, but with the reduced duration of dual antiplatelet therapy used with the TiNOX stent, we suggest that TiNOX stents may be an alternative to drug-eluting stents in patients unsuitable for long-term dual antiplatelet therapy.

Oversizing and restenosis with self-expanding stents in iliofemoral arteries.

PURPOSE: Uncoated self-expanding nitinol stents (NS) are commonly oversized in peripheral arteries. In current practice, 1-mm oversizing is recommended. Yet, oversizing of NS may be associated with increased restenosis. To provide further evidence, NS were implanted in porcine iliofemoral arteries with a stent-to-artery-ratio between 1.0 and 2.3. Besides conventional uncoated NS, a novel self-expanding NS with an antiproliferative titanium-nitride-oxide (TiNOX) coating was tested for safety and efficacy. METHODS: Ten uncoated NS and six TiNOX-coated NS (5-6 mm) were implanted randomly in the iliofemoral artery of six mini-pigs. After implantation, quantitative angiography (QA) was performed for calculation of artery and minimal luminal diameter. Follow-up was performed by QA and histomorphometry after 5 months. RESULTS: Stent migration, stent fracture, or thrombus formation were not observed. All stents were patent at follow-up. Based on the location of the stent (iliac/femoral) and the stent-to-artery-ratio, stent segments were divided into "normal-sized" (stent-to-artery-ratio < 1.4, n = 12) and "oversized" (stent-to-artery-ratio ≥ 1.4, n = 9). All stent segments expanded to their near nominal diameter during follow-up. Normal-sized stent segments increased their diameter by 6% and oversized segments by 29%. A significant correlation between oversizing and restenosis by both angiography and histomorphometry was observed. Restenosis rates were similar for uncoated NS and TiNOX-coated NS. CONCLUSIONS: TiNOX-coated NS are as safe and effective as uncoated NS in the porcine iliofemoral artery. All stents further expand to near their nominal diameter during follow-up. Oversizing is linearly and positively correlated with neointimal proliferation and restenosis, which may not be reduced by TiNOX-coating.

Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease.

AIM: Endothelial dysfunction is a marker for development and progression of atherosclerosis. Statin therapy improves endothelial function in cardiovascular patients by reducing LDL-cholesterol and by pleiotropic effects. B-group vitamin supplementation restores endothelial function mainly by reducing homocysteine-induced oxidative stress. Thus, we evaluated the effect of rosuvastatin, B-group vitamins and their combination on endothelial function in high-risk cardiovascular patients. METHODS: Thirty-six patients with cardiovascular disease were randomly, double-blinded assigned to either rosuvastatin 10 mg (group R, n = 18) or vitamin supplementation consisting of folic acid 1 mg, vitamin B12 0.4 mg, and B6 10 mg (group V, n = 18) for 6 weeks. After 6 weeks all patients received rosuvastatin and vitamin supplementation in combination for additional 6 weeks. Endothelial function was assessed by flow-mediated vasodilation (FMD) at baseline and after 6- and 12-week treatment. RESULTS: At baseline, FMD, plasma lipids, vitamins, and homocysteine were comparable between both groups. After 6 weeks, FMD improved in both groups (from 4.4 ± 1.6 to 6.9 ± 1.4% group R, P= 0.0004 and from 4.9 ± 1.8 to 6.4 ± 1.8% group V, P= 0.0002). This improvement in FMD was mainly associated with a decrease of plasma lipids in group R and a decrease of homocysteine in group V. After 12 weeks, the combined therapy with rosuvastatin and vitamins further improved FMD to the normal range in 26/33 patients compared to 5/36 at baseline (P < 0.0001). CONCLUSIONS: In conclusion, both treatments, rosuvastatin and B-group vitamin supplementation, improved endothelial function in high-risk cardiovascular patients. The combination of both therapies had an additive effect on endothelial function suggesting different mechanisms of action.

Comparison of arterial and venous coronary artery bypass flow measurements using 3-T magnetic resonance phase contrast imaging.

OBJECTIVE: Comparison of arterial and venous coronary artery bypass flow measurements using 3-T magnetic resonance (MR) phase contrast in correlation with intraoperative Doppler flow measurements. METHODS: Fifty-six coronary bypasses (right coronary artery n=18, left internal mammary artery to left anterior descending artery n=16, marginal artery n=7, circumflex artery n=7, diagonal artery n=6, left anterior descending artery n=1, and right internal mammary artery to right coronary artery n=1) were studied in 27 asymptomatic patients. In this prospective study, each bypass was studied intra-operatively using Doppler flow measurement. Within one week post surgery, patients were studied using a 3-T MR scanner (Magnetom Verio, Siemens, Erlangen, Germany) using velocity encoded phase-contrast flow measurements. RESULTS: Intraoperative Doppler flow measurements demonstrated regular flow patterns in all vascular territories supplied. All bypasses were patent on MRI and flow measurement results were as follows: median flow 60ml/min (interquartile range (IQR): 37.5-78.5ml/min). For comparison, the corresponding median intraoperative flow was 58ml/min (IQR: 41-80ml/min) (p<0.001; R=0.44). Linear regression analysis demonstrated a significant correlation for venous bypasses (p=0.0002; R=0.48), but not for arterial bypasses (p=0.09; R=0.24). CONCLUSION: This study demonstrated that MR flow measurements of venous bypass grafts agreed more with Doppler than arterial bypass grafts. However, bypass patency was confirmed for all patients. In the future, this technique may be used for non invasive coronary bypass graft follow-up.

Morphological and functional 3-Tesla magnetic resonance imaging of saphenous vein coronary artery bypass grafts.

Evaluation of a novel non-invasive tool for postoperative follow-up of patients postelective saphenous vein coronary artery bypass graft (CABG) was performed. Ten patients were included. Their bypass grafts supplied the right coronary artery (7), marginal branches (1), diagonal branches (2), and the circumflex artery (n=1). Each bypass was examined intraoperatively using Doppler flow measurement. Patients were examined with a 3-Tesla magnetic resonance imaging (MRI) scanner (MAGNETOM Verio, Siemens, Erlangen, Germany) within one week postsurgery using MR-angiography with an intravasal contrast agent and velocity encoded phase-contrast flow measurements. Intraoperative Doppler flow measurements revealed regular flow patterns in all vascular territories supplied. The median intraoperative flow rate was 50 ml/min with an inter-quartile range (IQR) of 42-70 ml/min. The clinical postoperative course was uneventful. MRI showed all grafts to be patent. The median postoperative flow rate was 50 ml/min (IQR: 32-65 ml/min). MRI flow rates agreed well with intraoperative Doppler flow measurements (mean difference: -2.8±20.1 ml/min). This initial study demonstrates that 3-Tesla MRI flow measurements correlated well with Doppler thus reconfirming the graft patency postCABG. Further refinement and broader application of this technique may facilitate follow-up postCABG potentially replacing empiric clinical judgment by reliable non-invasive imaging.

Assessment of right ventricular systolic function: comparison between cardiac magnetic resonance derived ejection fraction and pulsed-wave tissue Doppler imaging of the tricuspid annulus.

BACKGROUND: Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Its practical determination by echocardiography remains challenging. We compared routine assessment of lateral tricuspid annular systolic motion velocity (TV(lat), cm/s) using pulsed-wave tissue Doppler imaging from the apical 4-chamber view with cardiac magnetic resonance (CMR) as reference method. METHODS AND RESULTS: 254 individuals (43 ± 18 years) underwent both CMR (contiguous short axis slices; retrogated cine steady state free precession technique; manual contour tracing) and echocardiography within 2 ± 2 months. Seventy-five had coronary artery disease, 87 congenital heart disease, 17 dilated cardiomyopathy, 15 pulmonary artery hypertension, and 47 normal findings. RV ejection fraction (EF) by CMR was 51 ± 12% (range 17-78%). There was a linear correlation between RVEF and TV(lat) (r=0.60; p<0.0001). A TV(lat) cut-off of 12 cm/s identified patients with normal EF (≥50%) with 81% sensitivity and 68% specificity, and a threshold of TV(lat) <9 cm/s identified patients with severely reduced RVEF (<30%) with 82% sensitivity and 86% specificity. CONCLUSIONS: Systolic long-axis velocity measurements of the lateral tricuspid annulus allow a reliable assessment of RVEF in clinical routine. A threshold of TV(lat)<9 cm/s identifies patients with severely reduced RVEF (<30%) with high sensitivity and specificity.

Endothelial-cell-binding aptamer for coating of intracoronary stents.

UNLABELLED: Oligonucleotides capturing CD31 endothelial cells (= aptamer) were used for coating of intracoronary stents to improve endothelialization and vascular healing. METHODS: Three different coronary stents were implanted in 9 farm-raised swine: 1) cobalt-chromium stent (CC, control stent); 2) aminoparylene-coated stent (AP, polymer); and 3) aminoparylene- and aptamer-coated stent (AA). Stent length was 18 mm, stent diameter 3 mm. Animals were restudied after 6 weeks. Minimal lumen diameter (MLD) and late loss were determined by quantitative coronary angiography. Vessel lumen, intimal proliferation and restenosis were determined by histomorphometry. Disruption of the lamina elastica interna (LEI) and inflammatory reactions were assessed in all sections. RESULTS: The average MLD at baseline was 2.98 ± 0.65 mm and at follow up 2.18 ± 0.53 mm (p < 0.05, n = 27). Late loss and restenosis were smallest in CC and largest in AA (ns). Histomorphometry showed no significant differences between the three stents but there were inflammatory granulomas in 22% of all stents. A clear correlation between disruption of the LEI and inflammatory granulomas was observed. CONCLUSIONS: Stents coated with endothelial-cell-capturing aptamers show similar late loss and angiographic restenosis rates as uncoated cobalt-chromium stents. Neointimal proliferation was similar in all three stents suggesting comparable proliferative potentials. Inflammatory reactions were observed in 1 of 5 of all histologic sections. In the present study, no advantage of aptamer-coating on neointimal proliferation of intracoronary stents was found.

Impact of arterial injury on neointimal hyperplasia after implantation of drug-eluting stents in coronary arteries: an intravascular ultrasound study.

AIMS: We investigated the impact of arterial injury on neointimal hyperplasia following implantation of drug-eluting stents (DES). METHODS AND RESULTS: A total of 196 patients with 223 segments (sirolimus-eluting stents [SES]: 104, paclitaxel-eluting stents [PES]: 119) underwent intravascular ultrasound eight months after DES implantation. Arterial injury was defined as the balloon-to-artery ratio (BAR). Segments were categorised into two groups: high BAR defined as BAR>1.1 (120 segments), and low BAR defined as BAR < or =1.1 (103 segments). Baseline clinical characteristics were similar for both groups. Although reference vessel diameter was smaller, stent diameter, maximal balloon pressure and balloon diameter were higher in the high BAR compared with the low BAR group. Lumen (7.10±1.91 vs. 6.25±1.69, p=0.001), stent (7.31±1.95 vs. 6.41±1.80, p=0.001), and external elastic membrane (17.1±4.9 vs. 14.8±4.0, p<0.0001) areas (mm2) were higher, but neointimal hyperplasia (0.21±0.36 vs. 0.16±0.48, p=0.42) area (mm2) was similar in the high BAR compared with the low BAR group. Arterial injury as assessed by BAR was not associated with the amount of neointimal hyperplasia (R2=0.003, p=0.40). CONCLUSIONS: Arterial injury does not correlate with the amount of neointimal hyperplasia following DES implantation. Conventionally aggressive DES implantation techniques do not adversely affect long-term outcome with respect to restenosis.

A randomised determination of the Effect of Fluvastatin and Atorvastatin on top of dual antiplatelet treatment on platelet aggregation after implantation of coronary drug-eluting stents. The EFA-Trial.

Drug-drug interaction between statins metabolised by cytochrome P450 3A4 and clopidogrel have been claimed to attenuate the inhibitory effect of clopidogrel. However, published data regarding this drug-drug interaction are controversial. We aimed to determine the effect of fluvastatin and atorvastatin on the inhibitory effect of dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel. One hundred one patients with symptomatic stable coronary artery disease undergoing percutaneous coronary intervention and drug-eluting stent implantation were enrolled in this prospective randomised study. After an interval of two weeks under dual antiplatelet therapy with ASA and clopidogrel, without any lipid-lowering drug, 87 patients were randomised to receive a treatment with either fluvastatin 80 mg daily or atorvastatin 40 mg daily in addition to the dual antiplatelet therapy for one month. Platelet aggregation was assessed using light transmission aggregometry and whole blood impedance platelet aggregometry prior to randomisation and after one month of receiving assigned statin and dual antiplatelet treatment. Platelet function assessment after one month of statin and dual antiplatelet therapy did not show a significant change in platelet aggregation from 1st to 2nd assessment for either statin group. There was also no difference between atorvastatin and fluvastatin treatment arms. In conclusion, neither atorvastatin 40 mg daily nor fluvastatin 80 mg daily administered in combination with standard dual antiplatelet therapy following coronary drug-eluting stent implantation significantly interfere with the antiaggregatory effect of ASA and clopidogrel.

Pooled analysis of trials comparing titanium-nitride-oxide-coated stents with paclitaxel-eluting stents in patients undergoing coronary stenting.

We performed a pooled analysis of three trials comparing titanium-nitride-oxide-coated bioactive stents (BAS) with paclitaxel-eluting stents (PES) in 1,774 patients. All patients were followed for 12 months. The primary outcomes of interest were recurrent myocardial infarction (MI), death and target lesion revascularization (TLR). Secondary endpoints were stent thrombosis (ST) and major adverse cardiac events (MACE) including MI, death and TLR. There were 922 patients in the BAS group and 852 in the PES group. BAS significantly reduced the risk of recurrent MI (2.7% vs. 5.6%; risk ratio 0.50, 95% CI 0.31-0.81; p = 0.004) and MACE (8.9% vs. 12.6%; risk ratio 0.71, 95% CI 0.54-0.94; p = 0.02) during the 12 months of follow up. In contrast, the differences between BAS and PES were not statistically significant with respect to TLR (risk ratio 0.98, 95% CI 0.68-1.41), death (risk ratio 0.96, 95% CI 0.61-1.51) and definite ST (risk ratio 0.28, 95% CI 0.05-1.47). In conclusion, the results of this analysis suggest that BAS is effective in reducing TLR and improves clinical outcomes by reducing MI and MACE compared with PES.

Randomised comparison of titanium-nitride-oxide coated stents with bare metal stents: five year follow-up of the TiNOX trial.

AIMS: Revascularisation with Titanium-Nitride-Oxide (TiNOX) coated stents is safe and effective in patients with de novo native coronary artery lesions. In the TiNOX trial there was a reduction in restenosis and major adverse cardiac events as compared with stainless steel stents of otherwise identical design. The purpose of the present study was to evaluate the long-term outcome of these patients over five years. METHODS AND RESULTS: In 2003, 92 patients with de novo lesions were randomly assigned to treatment with TiNOX coated stents (n=45) or stainless steel stents (n=47; control). Baseline characteristics were similar in both groups. Follow-up at six months and five years was obtained in 87 patients. Five patients were lost to follow-up due to emigration or change in home address. At six months and five years, significantly less major adverse cardiac events (MACE) occurred in the TiNOX group (7% vs. 27%, [p=0.02] respectively and 16% vs. 39%, [p=0.03]), largely driven by a reduced need for target-lesion revascularisation. No stent thrombosis occurred in the TiNOX group vs. one in the control group. Patients in the TiNOX-group had lower all-cause mortality and less myocardial infarction, but the difference was not statistically significant. CONCLUSIONS: Five-year follow-up after implantation of titanium-nitride-oxide coated stents is favourable with a low rate of MACE and no stent thrombosis compared to bare metal stents of identical design. The need for revascularisation at five years was 9% in the TiNOX and 25% in the control group with little progression of native coronary disease.

Dual low response to acetylsalicylic acid and clopidogrel is associated with myonecrosis and stent thrombosis after coronary stent implantation.

BACKGROUND: Impaired response to antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel (CLO) has been associated with an increased risk of stent thrombosis and ischemic events after coronary stent implantation. We sought to investigate whether patients with a low response (LR) to ASA or CLO are at increased risk for periprocedural and short-term ischemic events after coronary stent implantation. METHODS: A total of 219 patients pretreated with ASA and CLO underwent percutaneous coronary intervention (PCI) with stent implantation. Whole blood impedance platelet aggregometry was performed with the Multiplate analyzer (Dynabyte, Munich, Germany) to test the response to ASA (ASPI test) and CLO (ADP test) within 12 to 18 hours after PCI. Patients were classified as ASA-LR, CLO-LR, dual LR, and controls. Study end points included myocardial infarction, stent thrombosis, and death assessed during the periprocedural period and at 30 days. RESULTS: Acetylsalicylic acid-LR was present in 34 (16%), CLO-LR in 33 (15%), and dual LR in 19 (9%) patients. Percutaneous coronary intervention-related myocardial infarction was encountered in 19 (9%) patients, with the highest incidence in dual-LR group (26.3%, P = .039). Composite ischemic events at 30 days were significantly more frequent in the dual-LR group than in other groups (36.8% vs 8.8% ASA-LR vs 6.1% CLO-LR vs 6.8% controls, P < .001). In multivariable analysis, dual LR (odds ratio 7.35, 95% CI 2.21-24.42, P < .001) and multivessel PCI (odds ratio 4.56, 95% CI 1.33-15.62, P = .016) were independently associated with ischemic events at 30 days. CONCLUSION: Dual LR to ASA and CLO is associated with an increased risk for short-term ischemic events after coronary stent implantation.

Computed tomographic coronary angiography in patients with surgically treated type A aortic dissection: preliminary results.

Acute type A aortic dissection is a serious emergency with a mortality rate of up to 40% within the first 24 h when left untreated. Surgical therapy needs to be initiated promptly. Due to this urgent situation, preoperative evaluation of the coronary arteries is not routinely performed in these patients. The aim of this study was to evaluate the accuracy of 64-slice computed tomography angiography (CTA) for postoperative coronary artery assessment in these patients. Ten consecutive patients with two or more cardiovascular risk factors were prospectively enrolled. Patients had type A aortic dissection treated surgically with a supracoronary graft of the ascending aorta. Performance of CTA to exclude significant stenosis (>50% lumen narrowing) and/or coronary artery dissection was compared with quantitative coronary angiography. A total of 147 segments were evaluated. Three segments (2%) were excluded from analysis. CTA correctly assessed one of three significant stenoses in three patients and correctly excluded coronary artery disease (CAD) in six of ten patients. One patient was rated false positive. Overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT for identifying coronary artery disease by segment was 98%, 33%, 99%, 50%, and 99%, respectively (P<0.05). By patient, it was 70%, 33%, 86%, 50%, and 75%, respectively. No coronary artery dissection was found. Noninvasive CTA may be a viable alternative to conventional angiography for postoperative coronary artery evaluation in patients with surgically treated type A aortic dissection and cardiovascular risk factors. An NPV of 99% should allow for reliable exclusion of CAD. Further studies with higher patient numbers are warranted.

Plasma homocysteine and cardiovascular risk in heart failure with and without cardiorenal syndrome.

INTRODUCTION: Plasma homocysteine (Hcy) has been associated with an increased cardiovascular (CV) risk in patients with chronic heart failure (CHF). Thus, we investigated whether Hcy has a prognostic impact on CV events in CHF-patients with and without cardiorenal syndrome (CRS). METHODS: 161 patients with CHF were included in the present analysis. 94 patients had systolic (SD) (EF <40%) and 67 diastolic (DD) dysfunction (EF>or=40%). 60 had cardiorenal syndrome (CRS+ creatinine clearance<60 ml/min). Mean ejection fraction was 38+/-16% (n=153) and mean VO2 max 19+/-7 ml/min (n=87). RESULTS: Homocysteine is significantly increased in patients with CHF (20+/-7 micromol/l). The increase correlates not only with the severity of the disease (NYHA, EF, VO2max), but also with various metabolic (BNP, uric acid) and nephrologic parameters (creatinine, creatinine clearance). During follow-up (23+/-37 months), patients with the highest homocysteine (>or=20 micromol/l) passed away more often (p<0.035) or decompensated more frequently (p<0.004) than those with a low Hcy. In patients with CRS the rate of decompensation was significantly higher than in those without CRS (p<0.0007). CONCLUSIONS: Homocysteine is an important marker for an increased CV risk in patients with CHF. A homocysteine of >/=20 micromol/l is associated with a high risk to decompensate or to die (odds ratio 2.57). The presence of CRS is also associated with an increased CV risk (odds ratio 3.7) and predicts an adverse clinical outcome.

Persistent diastolic dysfunction late after valve replacement in severe aortic regurgitation.

BACKGROUND: Regression of left ventricular (LV) hypertrophy with normalization of diastolic function has been reported in patients with aortic stenosis late after aortic valve replacement (AVR). The purpose of the present study was to evaluate the effect of AVR on LV function and structure in chronic aortic regurgitation early and late after AVR. METHODS AND RESULTS: Twenty-six patients were included in the present analysis. Eleven patients with severe aortic regurgitation were studied before, early (21 months) and late (89 months) after AVR through the use of LV biplane angiograms, high-fidelity pressure measurements, and LV endomyocardial biopsies. Fifteen healthy subjects were used as controls. LV systolic function was determined from biplane ejection fraction and midwall fractional shortening. LV diastolic function was calculated from the time constant of LV relaxation, peak filling rates, and myocardial stiffness constant. LV structure was assessed from muscle fiber diameter, interstitial fibrosis, and fibrous content. LV muscle mass decreased significantly by 38% early and 55% late after surgery. Ejection fraction was significantly reduced preoperatively and did not change after AVR (P=NS). LV relaxation was significantly prolonged before surgery (89+/-28 ms) but was normalized late after AVR (42+/-14 ms). Early and late peak filling rates were increased preoperatively but normalized postoperatively. Diastolic stiffness constant was increased before surgery (22+/-6 versus 9+/-3 in control subjects; P=0.0003) and remained elevated early and late after AVR (23+/-4; P=0.002). Muscle fiber diameter decreased significantly after AVR but remained increased at late follow-up. Interstitial fibrosis was increased preoperatively and increased even further early but decreased late after AVR. Fibrosis was positively linearly correlated to myocardial stiffness and inversely correlated to LV ejection fraction. CONCLUSIONS: Patients with aortic regurgitation show normalization of macroscopic LV hypertrophy late after AVR, although fiber hypertrophy persists. These changes in LV myocardial structure late after AVR are accompanied by a change in passive elastic properties with persistent diastolic dysfunction.