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Background: Whereas haemodialysis (HD) is lifesaving by replacement of renal function, there are data to suggest that the HD procedure itself may contribute to the high cardiac risk in dialysis patients. The HD procedure is associated with an increased risk of sudden death, and there is accumulating evidence that HD can elicit myocardial ischaemia. In this study, we evaluated the effect of HD on global and regional myocardial blood flow (MBF) and left ventricular (LV) function in non-diabetic, non-cardiac compromised patients., Methods: (13)N-NH(3) positron emission tomography (PET) was used to quantify changes in MBF, LV wall motion, cardiac output (CO), LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in seven non-diabetic patients with uneventful cardiac histories. PET scans were performed before and at 30 and 220 min of HD., Results: In all patients global MBF fell during HD. At 30 min of HD without ultrafiltration (UF), global MBF had fallen 13.5 +/- 11.5% (P < 0.05) while CO, LVEDV and LVESV were 4.6 +/- 5.3% (NS), 5.6 +/- 4.2% (P < 0.05) and 6.9 +/- 7.2% (P < 0.05) lower, respectively. At 220 min of HD, after UF of 2.5 +/- 0.9 l, global MBF had fallen 26.6 +/- 13.9% (P < 0.05) from baseline while CO, LVEDV and LVESV were 21.0 +/- 19.7%, 31.1 +/- 12.7% and 36.4 +/- 17.5% (all P < 0.05) lower, respectively. In two patients, new LV regional wall motion abnormalities (RWMA) developed at 220 min of HD. MBF was reduced to a greater extent in regions that developed LV RWMA compared to those that did not., Conclusions: Haemodialysis induced a pronounced fall in MBF. Since MBF fell already early during HD not only hypovolaemia but also acute dialysis-associated factors seem to play a role. Haemodialysis-associated reductions in MBF may contribute to the high cardiac event rate of dialysis patients.

Background: There is increasing evidence that plaque vulnerability, rather than the degree of stenosis, is important in predicting the occurrence of subsequent cerebral ischemic events in patients with carotid artery stenosis. The many imaging modalities currently available have different properties with regard to the visualization of the extent of vulnerability in carotid plaque formation., Methods: Original published studies were identified using the MEDLINE database (January 1966 to March 2008). Manual cross-referencing was also performed., Results: There is no single imaging modality that can produce definitive information about the state of vulnerability of an atherosclerotic plaque. Each has its own specific drawbacks, which may be the use of ionizing radiation or nephrotoxic contrast agents, an invasive character, low patient tolerability, or simply the paucity of information obtained on plaque vulnerability. Functional molecular imaging techniques such as positron emission tomography (PET), single photon emission-computed tomography (SPECT) and near infra-red spectroscopy (NIRS) do seem able accurately to visualize and even quantify features of plaque vulnerability and its pathophysiologic processes. Promising new techniques like near infra-red fluorescence imaging are being developed and may be beneficial in this field., Conclusion: There is a promising role for functional molecular imaging modalities like PET, SPECT, or NIRS related to improvement of selection criteria for carotid intervention, especially when combined with CT or MRI to add further anatomical details to molecular information. Further information will be needed to define whether and where this functional molecular imaging will fit into a clinical strategy.

Aims: To evaluate non-invasive angiography using dual-source computed tomography (CT) for the determination of the most appropriate therapeutic strategy in patients with suspected coronary artery disease (CAD)., Methods and Results: CT angiography (Dual Source CT, Somatom Definition, Siemens Medical Systems, Forchheim, Germany) was performed in 60 consecutive patients [51 men, median age 64 (57-70) years] scheduled for elective coronary angiography. Both techniques were used to evaluate the presence of CAD, significant stenosis, and the need for revascularization therapy. Sensitivity and specificity for the presence of significant stenosis were: per segment (n = 766) 62% (95% CI 50-72) (64/104) and 79% (95% CI 74-84) (526/662), respectively; per patient (n = 60) 100% (95% CI 91-100) (38/38) and 45% (95% CI 24-68) (10/22), respectively. In therapeutic decision-making based on CT angiography, sensitivity, specificity, positive and negative predictive values for intervention were 97% (95% CI 84-100) (36/37), 48% (95% CI 27-69) (11/23), 75% (95% CI 60-86) (36/48), and 92% (95% CI 60-100) (11/12), respectively. If a revascularization procedure was needed, the CT angiographic data indicated the appropriate modality (percutaneous coronary intervention or coronary artery bypass grafting) in 70% (26/36) of patients., Conclusion: Although imaging qualities have improved considerably, CT angiography cannot be used for definitive therapeutic decision-making with regard to revascularization procedures in patients with suspected CAD.

Objective: The aim of this study was to evaluate the value of attenuation correction (AC) of Tc-99m tetrofosmin single-photon emission tomography (SPECT) imaging for the assessment of left ventricular ejection fraction (LVEF)., Methods: Attenuation corrected and non-attenuation corrected (NC) resting Tc-99m tetrofosmin SPECT were compared for the assessment of LVEF. Planar multigated radionuclide angiography (MUGA) served as the reference for LVEF assessment. Patients (n = 56) with left ventricular dysfunction who underwent MUGA and rest gated Tc-99m tetrofosmin SPECT within 1 month were included., Results: The average LVEF on NC gated SPECT was 37.4 +/- 11.8% and on AC SPECT 38.5 +/- 13.4% (P = NS). The absolute mean difference of the LVEF between the MUGA and NC gated SPECT and AC gated SPECT was -0.2% (95% CI -1.7 to 1.3) and -1.3% (95% CI -2.7 to 0.03), respectively (P = NS both vs. MUGA). The correlation between NC gated SPECT and AC gated SPECT versus MUGA measurement was high with a correlation coefficient of 0.89 (P < 0.01) and 0.92 (P < 0.01), respectively. End-diastolic volumes (EDVs) and end-systolic volumes (ESVs) were significantly higher with AC gated SPECT when compared with NC gated SPECT (both P < 0.001)., Conclusions: Profile AC gated Tc-99m tetrofosmin SPECT agrees well with MUGA and NC gated Tc-99m tetrofosmin SPECT for the assessment of LVEF. EDVs and ESVs are significantly higher with AC gated SPECT when compared with NC gated SPECT.

Objective: This study was a pilot trial to determine safety and feasibility of intracoronary infusion of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction (MI)., Background: Studies reporting the effect of MBMC therapy on improvement of left ventricular (LV) function have shown variable results. The HEBE trial is a large multicenter, randomized trial that currently enrolls patients. Prior to this trial we performed a pilot study., Methods: Twenty-six patients with a first acute MI were prospectively enrolled in eight centers. Bone marrow aspiration was performed at a median of 6 days after primary PCI (interquartile range, 5-7 days). MBMC were isolated by gradient centrifugation and were infused intracoronary the same day. All patients underwent magnetic resonance imaging before cell infusion and after 4 months. Clinical events were assessed up to 12 months., Results: Within 10 hr after bone marrow aspiration, 246 +/- 133 x 10(6) MBMC were infused, of which 3.9 +/- 2.3 x 10(6) cells were CD34(+). In one patient, this procedure was complicated by local dissection. LV ejection fraction significantly increased from 45.0 +/- 6.3% to 47.2 +/- 6.5% (P = 0.03). Systolic wall thickening in dysfunctional segments at baseline improved with 0.9 +/- 0.7 mm (P < 0.001). Infarct size decreased 37% from 17.8 +/- 8.2 to 11.2 +/- 4.2 gram (P < 0.001). During 12-month follow-up, 3 additional revascularizations were performed and an ICD was implanted in one patient, 3 weeks after PCI., Conclusion: In patients with acute MI, intracoronary infusion of MBMC is safe in a multicenter setting. At 4-month follow-up, a modest increase in global and regional LV function was observed, with a concomitant decrease in infarct size., ((c) 2008 Wiley-Liss, Inc.)

The purpose of this study was to compare electron beam computed tomography (EBT) with transthoracic echocardiography (TTE) in determining aortic valve area (AVA). Thirty patients (9 females, 21 males) underwent a contrast-enhanced EBT scan (e-Speed, GE, San Francisco, CA, USA) and TTE within 17 +/- 12 days. In end-inspiratory breath hold, a prospectively ecg-triggered scan was acquired with a beam speed of 50-100 ms, a collimation of 2 x 1.5 mm and an increment of 3.0 mm. The AVA was measured with planimetry. A complete TTE study was performed in all patients, and the AVA was computed using the continuity equation. There was close correlation between AVA measured with EBT and AVA assessed with TTE (r = 0.60, P < 0.01). The AVA measured with EBT was 0.51 +/- 0.46 cm(2 )larger than the AVA calculated with TTE measurements. EBT appeared to be a valuable non-invasive method to measure the AVA. EBT measures the anatomical AVA, while with TTE the functional AVA is calculated, which explains the difference in results between the methods.

Objective: To investigate the feasibility of intracoronary application of endothelial progenitor cells and the subsequent distribution within the heart., Methods: Endothelial progenitors cells (EPCs) cultured from rat bone marrow were identified by double-positive staining with Dil-Ac-LDL and BS1-lectin. Twenty-four hours before cell transplantation, EPCs were labeled with 5-bromo-2'-deoxyuridine (BrdU). Cells (5 x 10(5) in 250-microl medium) were injected into healthy rats, either as intracoronary application (n=11) or as intramyocardial injection (n = 6). At 15 min or 3 days posttransplantation, hearts as well as other organs (lung, liver, kidney, and spleen) were collected and processed for subsequent BrdU immunohistochemistry. The number of BrdU-positive cells per tissue area was counted., Results: Compared to intramyocardial injection, intracoronary administration resulted in more than twice as much positive cells in the heart (P < .05), with no local differences within the heart. Whereas after 15 min, EPCs were equally distributed in all examined organs (except for the spleen), cells that were still present after 3 days, approximately 10%, were selectively restricted to the heart., Conclusions: Our data indicate that the intracoronary application provides a promising technique for EPC transplantation in the rat heart.

Objective: Repeated left ventricular ejection fraction (LVEF) analyses with sequential single-dose radionuclide ventriculography might be an interesting technique for monitoring the effect of positive inotropic interventions. The aim of the study was to assess the reproducibility of LVEF measurement with planar radionuclide ventriculography within 3 h, using a standard single dose of radioactive tracer., Methods: Sixteen patients underwent routine planar radionuclide ventriculography with a standard dose of 500 MBq of [Tc]pertechnetate and returned after 3 h for a repeat planar radionuclide ventriculography without administration of additional tracer., Results: The average initial LVEF was 35.1+/-18.6%-point (range, 12%-point to 68%-point). The mean difference of the LVEF between the initial planar radionuclide ventriculography and the repeat planar radionuclide ventriculography was 2.8%+/-6.3% (range, -11.8% to 13.3%, P=NS). The correlation between both measurements was significant with a correlation coefficient of 0.995 (P<0.01). Bland-Altman analysis revealed a mean LVEF difference of 0.94%-point between the baseline planar radionuclide ventriculography and the repeat planar radionuclide ventriculography (95% confidence interval: -2.7%-point to 4.5%-point). The visual wall motion assessment showed excellent reproducibility, with a kappa-statistic of 0.98., Conclusion: Repeated radionuclide ventriculography with a 3 h interval using a single standard dose of 500 MBq of [Tc]pertechnetate is highly reproducible and will be useful for monitoring the effect of positive inotropic interventions.

The effect of preprocedural fibrinogen levels on in-stent restenosis is largely unknown. The -455G/A polymorphism of the fibrinogen beta-gene is associated with baseline plasma level or acute phase increase of fibrinogen. Therefore, we hypothesized that there is a relationship between this polymorphism and preprocedural fibrinogen level and clinical restenosis at follow-up among patients with coronary stent placement. The GENetic DEterminants of Restenosis (GENDER) project is a multicenter follow-up study that enrolled 3,146 consecutive patients after successful percutaneous coronary intervention. A coronary stent was placed in 2,309 patients. Of these, 2,257 (97.7%) patients were successfully genotyped for the -455G/A polymorphism. Plasma fibrinogen levels were measured at baseline in a subpopulation of 623 stented patients with the von Clauss method and patients were grouped into tertiles according to fibrinogen levels. Primary endpoint was target vessel revascularization (TVR); secondary combined endpoint was defined as death presumably from cardiac causes, MI not attributable to another coronary artery than the target vessel, and TVR. No association was observed between the -455G/A polymorphism and TVR or combined endpoint (p=0.99, p=0.97, respectively). Multivariate regression analysis revealed that the risk of TVR and combined endpoint was not higher for patients in the highest tertile for fibrinogen versus the lowest tertile (RR=0.60, 95% CI: 0.26-1.37 for TVR, RR=0.64, 95% CI: 0.29-1.44 for combined endpoint). In conclusion, the presence of -455G/A polymorphism in the fibrinogen beta-gene and preprocedural fibrinogen level is not associated with an increased risk of TVR or combined endpoint in a patient population with coronary stent placement. Therefore, these parameters are not worthwhile for stratifying patients at risk for restenosis pre-stenting.

Unlabelled: The purpose of this study was to appraise the value of PET in the assessment of the effect of supposedly proangiogenic new therapies such as gene therapy with vascular endothelial growth factor (VEGF) gene and endomyocardial laser therapy., Methods: Thirty-five patients with end-stage coronary artery disease and class III (Canadian Cardiovascular Society) angina were included. Myocardial ischemia was evaluated with dipyridamole PET scanning and exercise tolerance with bicycle ergometry. Ten patients were treated with naked plasmid DNA encoding for human VEGF165 (VEGF) and 12 patients were treated with laser therapy (direct myocardial revascularization [DMR]) using an electromechanical mapping system. Thirteen patients were treated with standard medical therapy (control)., Results: In both active treatment groups, angina was reduced in most subjects, except in 2 VEGF and 5 DMR patients. In the control group, no improvement in anginal classification was found, except in 3 subjects. On the PET scan, solely in the VEGF group, the stress perfusion was significantly improved (from 57 +/- 33 to 81 +/- 55 mL/min/100 g; P = 0.031). Furthermore, in the VEGF group, the number of ischemic segments was reduced from 274 +/- 41 to 234 +/- 48 segments (P = 0.004) but not in the DMR group (from 209 +/- 43 to 215 +/- 52 segments) or in the control group (from 218 +/- 18 to 213 +/- 28 segments). Bicycle exercise duration showed slight nonsignificant changes in the VEGF group (from 3.6 +/- 2.0 to 4.6 +/- 2.1 min), in the DMR group (from 5.1 +/- 1.5 to 4.7 +/- 1.3 min), and in the control group (from 3.3 +/- 1.8 to 3.5 +/- 2.3 min)., Conclusion: PET showed that intramyocardial gene therapy with the human VEGF165 gene in contrast to laser DMR treatment effectively reduces myocardial ischemia.

Background: The aim of this study was to evaluate the combination of a silicon carbide-coated stent with the periprocedural use of abciximab in patients with type B2/C lesions. The study was a prospective cohort study and was conducted at the University Medical Center of Groningen., Methods: Elective percutaneous transluminal coronary angioplasty was performed in a total of 44 patients. All had lesions with type B2/C characteristics and most were relatively small, tortuous and calcified. The involved vessel segment was stented. Silicon carbide-coated stents were used in combination with periprocedural abciximab. The main outcome measures were cardiac death, target vessel revascularization, myocardial infarction, and cerebrovascular accident., Results: At 6 months of follow-up, only 4 patients had a major adverse cardiac event. Three patients had undergone target vessel revascularization and 1 patient had suffered from a cerebrovascular accident. Sixteen patients underwent re-angiography 6 months after the initial procedure. The average stenosis at 6 months was 15% with a minimal lumen diameter of 2.4 mm., Conclusions: A 9% major adverse cardiac event rate and a 7% target vessel revascularization rate at 6 months in type B2/C lesions were recorded. Further investigation on the use of this specific treatment combination is warranted.

Aims: To document the practice of interventional cardiology and the clinical restenosis rate, as well as the risk factors for clinical restenosis in an unselected population of patients in daily practice and to provide a perspective for the need of new devices such as drug-eluting stents., Methods and Results: A total of 3177 consecutive patients, who underwent successful percutaneous transluminal coronary angioplasty (PTCA) in the Netherlands, were included. Patients with acute myocardial infarction were excluded. The pre-defined end-point of clinical restenosis was defined as cardiac death, myocardial infarction and revascularisation of the target vessel. Follow-up (9.6 months, IQR 3.9) was complete in 3146 (99.3%) patients with a mean age of 62.1+/-10.7 years. Of them 896 (28.5%) were female, 459 (14.6%) had diabetes and 1459 (46.4%) had multi-vessel disease. Most patients (2105, 66.9%) were treated for stable angina. Of all patients, 819 (26.0%) were treated for multiple lesions, 2340 (74.4%) underwent stenting and 820 (26.1%) received glycoprotein IIb/IIIa inhibitors. All stented patients received life-long aspirin and ticlopidin/clopidogrel during at least 1 month after the procedure. Target vessel revascularisation during follow-up by either coronary artery by-pass grafting (CABG) or PTCA was necessary in 304 patients (9.7%). Thirty-three (1.1%) patients died of cardiac disease and 22 (0.7%) patients suffered from myocardial infarction (MI) attributable to the originally treated vessel. Overall, the need for revascularisation, or the incidence of cardiac death or MI occurred in 346 patients (11.0%), at 9 and 12 months these event-rates were 10.2% and 12.0%, respectively. Diabetes, hypertension, peripheral vessel disease, multi-vessel disease and treatment of type C lesions prevailed as independent risk factors for clinical restenosis. Longer stents and smaller minimal stent diameter were risk factors for in-stent stenosis., Conclusion: In this unselected series of consecutive patients treated for stable and unstable angina in everyday clinical practice in the pre-drug-eluting stent era, clinical restenosis after 9 and 12 months follow-up of the patients occurred in 10.2% and 12.0%, respectively. The risk varies from 8.3% to 17.6% depending on the number of risk factors. A proper selection of patients that benefit from new devices warranted, since the vast majority are well-treated with standard techniques and proper assignment of expensive new devices is obviously of importance for overall health care.

Background: As endothelial dysfunction can be responsible for myocardial ischemia even in the absence of significant coronary lesions, we aimed to assess the correlation between endothelium-dependent vasomotor function and inducible ischemia late after successful coronary angioplasty., Methods: In 30 patients without angiographic restenosis or coronary disease progression, coronary endothelial function was determined by acetylcholine infusion 6 months after elective single-vessel stenting of the left coronary artery. Acetylcholine-induced diameter changes were assessed in the proximal and distal segments of both the stented and the contralateral vessels by means of quantitative coronary angiography. A maximal workload ergometric test was also performed prior to endothelial function testing., Results: Acetylcholine induced significant vasoconstrictive responses in the distal but not in the proximal segments of both the stented (-11 +/- 7% versus baseline; p < .01) and the contralateral vessels (-11 +/- 6%; p < .01), which were significantly correlated (R = .48; p < .05) and were completely reverted by nitroglycerine. Inducible ischemia was the only predictive factor for distal vasoconstriction in the stented vessel (p < .01) but not in the contralateral vessel (p = .06). Patients with minor signs of ischemia at the ergometric test showed a greater vasoconstriction than those with a completely normal test (-16 +/- 7% versus -7 +/- 6%; p< .01)., Conclusions: Exercise-induced ischemia late after successful percutaneous coronary intervention is related to distal coronary endothelial dysfunction.

Background: Endothelial dysfunction is useful in predicting future cardiovascular disease. At present several tests are available to test endothelial function: coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to acetylcholine, and brachial artery flow-mediated dilative (FMD) response to postischemic hyperemia. This study aimed to compare the three most frequently reported endothelial function tests., Methods: Twenty-eight patients (19 males and nine females, mean age 57 years) referred for diagnostic coronary angiography were considered for endothelial function measurement in the coronary artery as well as in the forearm by FBF and FMD., Results: Acetylcholine decreased the mean coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%). Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of acetylcholine on forearm resistance vessels was significantly related to the effect of acetylcholine on the coronary conduit vessels (P=0.039). Nonetheless, FMD was not related to FBF nor to the coronary response., Conclusion: In patients with mild coronary endothelial dysfunction, forearm vasoreactivity is related to the coronary response, provided that the same stimulus is used.