Lutz Klinghammer

Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets

OBJECTIVE To investigate whether CD40L/CD154 on platelets and soluble CD40L/CD154 may play a role in the inflammatory process of acute coronary syndromes. DESIGN AND SETTING Observational study in a university hospital. PATIENTS 15 patients with acute myocardial infarction, 25 patients with unstable angina, 15 patients with stable angina, and 12 controls. MAIN OUTCOME MEASURES CD40L/CD154 on platelets, P-selectin/CD62P on platelets, soluble CD40L/CD154 serum concentrations. RESULTS Mean (SD) CD40L/CD154 expression on platelets was 6.2 (2.8) MFI (mean fluorescence intensity) in the infarct group, 11 (3.3) MFI in the unstable angina group (p < 0.001 v infarction), 3.6 (0.9) MFI in the stable angina group (p < 0.01 vinfarction; p < 0.001 v unstable angina), and 3.2 (1.0) MFI in the controls (p < 0.01v infarction; p < 0.001v unstable angina; NSv stable angina). Soluble CD40L/CD154 concentration was 5.2 (1.1) ng/ml in the infarct group, 4.2 (0.7) ng/ml in the unstable angina group (p < 0.001v infarction), 2.9 (1.0) ng/ml in stable angina group (p < 0.001 v infarction and unstable angina), and 3.0 (0.5) ng/ml in the controls (p < 0.001v infarction and unstable angina; NSv stable angina). At a six months follow up, there was lower expression of CD40L/CD154 on platelets in patients with unstable angina (12.3 (3.6) v 3.8 (1.2) MFI, p < 0.0001) and acute myocardial infarction (6.2 (2.8)v 3.5 (0.8) MFI, p < 0.01) compared with their admission values six months earlier. Patients with unstable angina who needed redo coronary angioplasty (PTCA) or who had recurrence of angina were characterised by increased CD40L/CD154 expression on platelets compared with the remainder of the study group (recurrence of angina: 12.7 (3.2) v 9.7 (1.6) MFI, p < 0.05; re-do PTCA: 14.3 (4.2) v10.3 (2.1) MFI, p < 0.05). CONCLUSIONS Both CD40L/CD154 on platelets and soluble CD40L/CD154 are raised in patients with unstable angina and myocardial infarction. These findings suggest that CD40–CD40L/CD154 interactions may play a pathogenic role in triggering and propagation of acute coronary syndromes.

Transradial approach for coronary angioplasty in the setting of acute myocardial infarction: A dual-center registry

Although transradial angioplasty has been shown to have no major entry site–related complications, its clinical applicability for balloon angioplasty and stenting in acute myocardial infarction (AMI) is unclear. In order to assess the feasibility, safety, and clinical outcome of transradial access for coronary angioplasty (PTCA) and stenting during AMI, transradial angioplasty for AMI was registered on a prospective database at two European sites (A and B) with experience in the radial approach (RA); 6 Fr catheters with an inner lumen of at least 0.064″ and low‐profile rapid‐exchange balloons were used. Primary success rates and procedural complications of 6 Fr RA were determined and compared to 6 Fr femoral approach (FA) procedures. A total of 1,224 AMI patients entered the registry. Study site A enrolled 185 RA patients (13.6% AMI) and study site B 92 RA patients (63.4%). Patient baseline demographics were similar in both study centers and showed no differences between RA and FA patients, except a more frequent use of abciximab in study site B compared to A. PTCA was successful in > 95% of both RA and FA patients. Total procedural time did not differ between RA and FA patients. Severe access site–related bleeding complications, however, were observed in FA patients only: study site A used closure devices routinely and found 2% severe bleedings; study site B used no closure device for FA patients and observed 7% severe bleedings. In selected patients and in experienced hands, transradial PTCA in AMI has a high success rate, is clinically safe, and could become an attractive alternative access site for patients being at high or even low risk for bleeding complications. Cathet Cardiovasc Intervent 2002;55:206–211.

Simultaneous hemodialysis during coronary angiography fails to prevent radiocontrast-induced nephropathy in chronic renal failure.

BACKGROUND Radiocontrast medium- (RM) associated nephrotoxicity continues to be a common cause of acute renal failure and may lead in patients with pre-existing chronic renal insufficiency even to end-stage renal failure requiring chronic dialysis. Since extracorporeal removal of RM after RM administration has been shown to be effective but does not prevent radiocontrast-induced nephropathy, the effect of a simultaneous dialysis during RM administration on renal function is not clear. METHODS In a prospective, randomized and controlled trial, we studied the effect of a 4-hour online dialysis during RM (iomeprol) application in patients with advanced chronic renal failure (serum creatinine > or = 3 mg/dl) undergoing coronary angiography. All patients received hydration with saline before and after standardized coronary angiography and were randomized to receive a simultaneous high-flux hemodialysis (7 patients, HD group) or to control group (10 patients). 24-hour creatinine clearance (CrCl) was measured in all patients before, 1 week and 8 weeks after coronary angiography. The clinical follow-up comprised 8 weeks after RM application. RM plasma levels were measured in both groups 15, 30, 60 minutes, 2, 4, 12, 24, 48 and 72 hours after application by high-pressure liquid chromatography. RESULTS At baseline, CrCl (19 +/- 10 vs 17 +/- 7 ml/min), percentage of diabetics (57 vs 70%) and dose of RM (77 +/- 27 vs 86 +/- 21 ml) were similar in both groups. Pharmacokinetics: Total clearance of iomeprol was significantly higher (54 +/- 15 vs 20 +/- 12 ml/min, p < 0.001) and the area under curve (AUC) was significantly lower (23 +/- 10 g x h/l vs 94 +/- 57 g x h/l, p < 0.001) in the HD group compared to control group. RM peak plasma levels 15 min after application were not different in both groups (3.0 +/- 1.1 vs 4.2 +/- 1.7 mmol/l, NS), however, significantly lower 60 min (1.6 +/- 0.4 vs 3.7 +/- 1.5 mmol/l, p < 0.01) and 240 min (0.7 +/- 0.3 vs 2.3 +/- 0.7 p < 0.001) after angiography. CLINICAL RESULTS CrCl showed no difference 1 week (24 +/- 11 vs 19 +/- 9 ml/min, ns) and 8 weeks (24 +/- 5 vs 20 +/- 9 ml/min, NS) after angiography from baseline or between the groups. In each group, 2 patients developed end-stage renal disease and requested permanent dialysis during the 8-week follow-up. CONCLUSION Simultaneous dialysis reduces AUC of iomeprol significantly, however, does not influence plasma peak concentration after angiography. Renal function and incidence of end-stage renal failure were not influenced by online-dialysis.

Usefulness of magnetocardiography for the investigation of fetal arrhythmias

The electrical excitation of the heart causes weak magnetic fields that can be recorded without skin contact over the body surface. Cardiac magnetic activity measures in the range of 0.2 to 5 picotesla (pT) in fetuses and 50 pT in adults, thus approximately 1 million times weaker than the static magnetic field of the earth. Therefore, it was not until the introduction of highly sensitive Superconducting Quantum Interference Device detectors and multichannel equipment that sensitive and low-noise registrations of cardiac magnetic fields became feasible in clinical practice. In 1974, the first fetal “magnetocardiogram” was published by Kariniemi and coworkers 1 ; later studies demonstrated the ability of magnetocardiography (MCG) to detect noninvasively fetal cardiac activity with high resolution and success rates from the second trimester onward. 2‐ 4 MCG provides information equivalent to the surface electrocardiogram (ECG), which is obviously unsuccessful in fetuses. Especially in late pregnancy, the signal of the fetal ECG is severely attenuated due to the insulating properties of the vernix caseosa and volume conduction effects. 5 Although Doppler echocardiography constitutes the gold standard for the analysis of fetal arrhythmias, MCG offers insights into electrophysiologic features of prenatal arrhythmias. An increasing number of recent publications emphasize interest in this field. 6‐ 9 In the present study, we investigated the feasibility of MCG in a clinical work routine to

Accuracy of prospectively ECG-triggered very low-dose coronary dual-source CT angiography using iterative reconstruction for the detection of coronary artery stenosis: comparison with invasive catheterization

OBJECTIVE To evaluate the image quality and diagnostic accuracy of very low-dose computed tomography (CT) angiography (CTA) for the evaluation of coronary artery stenosis. BACKGROUND Iterative reconstruction (IR) has shown to substantially reduce image noise and hence permit the use of very low-dose data acquisition protocols in coronary CTA. METHODS Fifty symptomatic patients with an intermediate likelihood for coronary artery disease underwent coronary CTA (heart rate: 59 ± 5 bpm, prospectively ECG-triggered axial acquisition, 100 kV, 160 mAs, 2 × 128 × 0.6 mm collimation, 60 mL contrast, 6 mL/s) prior to invasive coronary angiography. CTA images were reconstructed using both standard filtered back projection (FBP) and a raw data-based IR algorithm [Sinogram Affirmed Iterative Reconstruction (SAFIRE), Siemens Healthcare]. Subjective image quality (four-point Likert scale from 0 = non-diagnostic to 3 = excellent image quality), image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), as well as the presence of coronary stenosis >50% were independently determined by two observers. RESULTS The mean dose-length product was 46.8 ± 3.5 mGy cm (estimated effective dose 0.66 ± 0.05 mSv). IR led to significantly improved objective image quality compared with FBP (image noise: 41 ± 12 vs. 49 ± 11 HU, P < 0.0001; CNR: 16 ± 8 vs. 12 ± 4, P < 0.0001; SNR: 13 ± 7 vs. 10 ± 3, P < 0.0001). Four coronary segments were not evaluable on FBP data, whereas all segments showed diagnostic image quality with IR. To detect significant coronary stenosis, sensitivity, specificity, positive predictive value, and negative predictive value were 69% (11/16), 97% (175/180), 69% (11/16), and 97% (175/180) per vessel with FBP data sets, respectively. With IR data sets, the corresponding values were 81% (13/16), 97% (178/184), 68% (13/19), and 98% (178/181). These differences were not statistically significant (P = 0.617). CONCLUSIONS Raw data-based IR significantly improves image quality in very low-dose prospectively ECG-triggered coronary dual-source CTA when compared with standard reconstruction using FBP.

Predictive value of the decrease in circulating dendritic cell precursors in stable coronary artery disease

DCs (dendritic cells) are present in atherosclerotic lesions leading to vascular inflammation, and the number of vascular DCs increases during atherosclerosis. Previously, we have shown that the levels of circulating DCPs (DC precursors) are reduced in acute coronary syndromes through vascular recruitment. In the present study, we have investigated whether DCP levels are also reduced in stable CAD (coronary artery disease). The levels of circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs) and tDCP (total DCPs) were investigated using flow cytometry in 290 patients with suspected stable CAD. A coronary angiogram was used to evaluate a CAD score for each patient as follows: (i) CAD excluded (n=57); (ii) early CAD (n=63); (iii) moderate CAD (n=85); and (iv) advanced CAD (n=85). Compared with controls, patients with advanced stable CAD had lower HDL (high-density lipoprotein)-cholesterol (P=0.03) and higher creatinine (P=0.003). In advanced CAD, a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.001). A significant inverse correlation was observed between the CAD score and mDCPs, pDCPs or tDCPs (each P<0.001). Patients who required percutaneous coronary intervention or coronary artery bypass grafting had less circulating mDCPs, pDCPs and tDCPs than controls (each P<0.001). Multiple stepwise logistic regression analysis suggested mDCPs, pDCPs and tDCPs as independent predictors of CAD. In conclusion, we have shown that patients with stable CAD have significantly lower levels of circulating DCPs than healthy individuals. Their decrease appears to be an independent predictor of the presence of, and subsequent therapeutic procedure in, stable CAD.

Red blood cell omega-3 fatty acids and the risk of ventricular arrhythmias in patients with heart failure

BACKGROUND Epidemiological studies support the protective effect of omega-3 fatty acids on sudden cardiac death. However, patients with structural heart disease and an implantable cardioverter defibrillator (ICD) showed no effect or even a proarrhythmic response to fish oil supplementation. Animal studies suggest different electrophysiologic effects of circulating and incorporated omega-3 fatty acids. METHODS In 102 ICD patients in New York Health Association functional class II or III, the fatty acid composition of red blood cells was analyzed by gas chromatography. The omega-3 index was calculated from eicosapentaenoic acid and docosahexaenoic acid. Patients were followed for 1 year, and ventricular arrhythmias requiring antitachycardic therapy were analyzed. Twenty-five healthy subjects served as control. RESULTS In ICD patients, the fatty acid profile was significantly altered and the baseline omega-3 index was significantly elevated, as compared to control subjects (5.12% +/- 0.87% vs 4.24% +/- 0.96%, P < .001). Kaplan-Meier estimates of probability of ventricular arrhythmias showed significant differences among quartiles of the omega-3 index. Twelve percent of patients in the lowest quartile had ventricular arrhythmias, as compared to 54% of patients in the highest quartile (P = .022). In a multivariate analysis, the omega-3 index was the only independent predictor for ventricular arrhythmias up to 9 months. At 12 months, a reduced ejection fraction was an additional risk predictor. CONCLUSIONS In heart failure patients, the red blood cell fatty acid profile is altered. Omega-3 fatty acids are elevated and predict the risk of ventricular arrhythmias.

Low-Dose Dual-Source CT Angiography With Iterative Reconstruction for Coronary Artery Stent Evaluation

OBJECTIVES The purpose of this study was to evaluate the image quality and diagnostic accuracy of very low-dose, dual-source computed tomography (DSCT) angiography for the evaluation of coronary stents. BACKGROUND Iterative reconstruction (IR) leads to substantial reduction of image noise and hence permits the use of very low-dose data acquisition protocols in coronary computed tomography angiography. METHODS Fifty symptomatic patients with 87 coronary stents (diameter 3.0 ± 0.4 mm) underwent coronary DSCT angiography (heart rate, 60 ± 6 beats/min; prospectively electrocardiography-triggered axial acquisition; 80 kV, 165 mA, 2 × 128 × 0.6-mm collimation; 60 ml of contrast at 6 ml/s) before invasive coronary angiography. DSCT images were reconstructed using both standard filtered back projection and a raw data-based IR algorithm (SAFIRE, Siemens Healthcare, Forchheim, Germany). Subjective image quality (4-point scale from 0 [nondiagnostic] to 3 [excellent image quality]), image noise, contrast-to-noise ratio as well as the presence of in-stent stenosis >50% were independently determined by 2 observers. RESULTS The median dose-length product was 23.0 (22.0; 23.0) mGy · cm (median estimated effective dose of 0.32 [0.31; 0.32] mSv). IR led to significantly improved image quality compared with filtered back projection (image quality score, 1.8 ± 0.6 vs. 1.5 ± 0.5, p < 0.05; image noise, 70 Hounsfield units [62; 80 Hounsfield units] vs. 96 Hounsfield units [82; 113 Hounsfield units], p < 0.001; contrast-to-noise ratio, 11.0 [9.6; 12.4] vs. 8.0 [6.2; 9.3], p < 0.001). To detect significant coronary stenosis in filtered back projection reconstructions, the sensitivity, specificity, positive predictive value, and negative predictive value were 97% (32 of 33), 53% (9 of 17), 80% (32 of 40), and 90% (9 of 10) per patient, respectively; 89% (43 of 48), 79% (120 of 152), 57% (42 of 74), and 96% (121 of 126) per vessel, respectively; and 85% (12 of 14), 69% (51 of 73), 32% (11 of 34), and 96% (51 of 53) per stent, respectively. In reconstructions obtained by IR, the corresponding values were 100% (33 of 33), 65% (11 of 17), 85% (33 of 39), and 100% (11 of 11) per patient, respectively; 96% (46 of 48), 84% (129 of 152), 66% (47 of 71), and 98% (127 of 129) per vessel, respectively; and 100% (14 of 14), 75% (55 of 73), 44% (14 of 32), and 100% (55 of 55) per stent, respectively. These differences were not significant. CONCLUSIONS In selected patients, prospectively electrocardiography-triggered image acquisition with 80-kV tube voltage and low current in combination with IR permits the evaluation of patients with implanted coronary artery stents with reasonable diagnostic accuracy at very low radiation exposure.

Comparison of Intracoronary Versus Intravenous Administration of Adenosine for Measurement of Coronary Fractional Flow Reserve

Background—Measurement of fractional flow reserve (FFR) constitutes the current gold standard to evaluate the hemodynamic significance of coronary stenoses. Limited data validate the intracoronary application of adenosine against standard intravenous infusion. We systematically compared FFR measurements during intracoronary and intravenous application of adenosine about agreement and reproducibility. Methods and Results—We included 114 patients with an intermediate degree of stenosis in coronary angiography. Two FFR measurements were performed during intracoronary bolus injection (40 &mgr;g for the right and 80 &mgr;g for the left coronary artery, FFRic), and 2 FFR measurements during continuous intravenous infusion of adenosine (140 &mgr;g/kg per minute, FFRiv). FFR value, the time to reach FFR and patient discomfort (on a subjective scale from 0 for no symptoms to 5 for maximal discomfort) were recorded for each measurement. Mean time to FFR was 100±27 s for continuous intravenous infusion versus 23±14 s for intracoronary bolus administration of adenosine (P<0.001). Reported discomfort after intracoronary application was significantly lower compared with intravenous adenosine (subjective scale >0 in 35.1% versus 87.7% of the patients; P<0.001). Correlation between FFRiv and FFRic was extremely close (r=0.99; P<0.001) with no systematic bias in Bland–Altman analysis (bias 0.002 [confidence interval, −0.001 to 0.005]) and low intermethod variability (1.56%). Intramethod variability was not different between intravenous and intracoronary administration (1.47% versus 1.33%; P=0.5). Conclusions—Intracoronary bolus injection of adenosine (40 &mgr;g for the right and 80 &mgr;g for the left coronary artery) yields identical FFR results compared with intravenous infusion (140 &mgr;g/kg per minute), while requiring less time and offering superior patient comfort.

Comparison of Dual-Source Computed Tomography for the Quantification of the Aortic Valve Area in Patients With Aortic Stenosis Versus Transthoracic Echocardiography and Invasive Hemodynamic Assessment

We compared the measurements of the aortic valve area (AVA) using dual-source computed tomography (DSCT) in patients with mid to severe aortic stenosis to measurements using transthoracic echocardiography (TTE) and invasive hemodynamic assessment. A total of 50 patients (mean age 73 +/- 10 years) with suspected aortic stenosis were included. The computed tomographic data were acquired using DSCT with standardized scan parameters (2 x 64 x 0.6 mm collimation, 330-ms rotation, 120-kV tube voltage, 560 mA/rot tube current). After injection of 35 ml contrast agent (flow rate 5 ml/s), a targeted volume data set, ranging from the top of the leaflets to the infundibulum, was acquired. Ten cross-sectional data sets (slice thickness 1 mm, no overlap, increment 0.6 mm) were reconstructed during systole in 5% increments of the R-R interval. The AVA determined in systole by planimetry was compared to the calculated AVA values using the continuity equation on TTE and the Gorlin formula on catheterization. DSCT allowed the planimetry of the AVA in all patients. The mean AVA using DSCT was 1.16 +/- 0.47 cm(2) compared to a mean AVA of 1.04 +/- 0.45 cm(2) using TTE and 1.06 +/- 0.45 cm(2) using catheterization, with a significant correlation between DSCT/TTE (r = 0.93, p <0.001) and DSCT/cardiac catheterization (r = 0.97, p <0.001). However, DSCT demonstrated a slight, but significant, overestimation of the AVA compared to TTE (+0.12 +/- 0.17 cm) and catheterization (+0.10 +/- 0.12 cm(2)). In conclusion, DSCT permits one to assess the AVA with a high-image quality and diagnostic accuracy compared to TTE and invasive determination.