Biomedical subjects

Christian Hamm

Publications and source records attributed to Christian Hamm.

23 records · Page 2Linked to original sources

PubMed2004

Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death.

OBJECTIVES: The aim of the present study was to objectify the loss of myocytes and the mechanism by which myocytes die in human hibernating myocardium (HHM). BACKGROUND: Intracellular degeneration, reduced cellular protein synthesis, and the replacement fibrosis contribute to structural disintegration of HHM. METHODS: In 14 patients, HHM was diagnosed by dobutamine echocardiography, radionuclide ventriculography, and thallium-201 scintigraphy. Functional recovery was documented by repeating the preoperative clinical investigations three months after successful coronary artery bypass graft surgery (CABG). During CABG, transmural biopsies were taken from the center of HHM regions and studied by electron microscopy, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, reverse transcription-polymerase chain reaction, and Western blotting. Control samples were taken from nondiseased human myocardium. RESULTS: All patients showed significant improvement or normalization of the regional function of HHM. Ubiquitin-related autophagic cell death was evident ultrastructurally by the occurrence of autophagic vacuoles, cellular degeneration, and nuclear disassembly. Ubiquitin-protein complexes were found in 0.03 +/- 0.008% (control: 0%, p < 0.005) of all myocytes. The proteasome 20S subunit/total myocytes were reduced from 63.3 +/- 9.6% in control myocardium to 36.9 +/- 8.4% in HHM. Complement-9, indicating oncosis, was found in only one of 14 biopsies. TUNEL-positive myocytes were 0.002 +/- 0.0003%. Electron microscopy showed apoptotic cells in 3 of 14 samples. However, the bcl-2/bax ratio was significantly reduced. Moreover, caspase-3 messenger ribonucleic acid was 8.5 times upregulated, and caspase-3 was activated. Cell death was absent in controls. CONCLUSIONS: In HHM, ubiquitin-related autophagic cell death and apoptosis cause a loss of myocytes. This plays an important role in progressive tissue damage and causes a reduction of the extent of functional recovery of HHM.

Aged↗

PubMed2004

Angiographic outcome in multivessel disease (GABI II study) using new coronary device interventions and comparison with GABI I trial results.

Percutaneous coronary interventions using stents were investigated in patients with multivessel disease. Acute and long-term results were compared with those of the German Angioplasty Bypass Surgery Investigation trial in a prospective multicenter study. The study included 134 patients in whom 277 lesions were treated. Angiographic success and procedural success were achieved in 268 of 277 lesions (97%) and 118 of 134 patients (88%), respectively. Control angiography performed in 90 of 118 eligible patients (76%) exhibited restenosis in 43 of 182 lesions (24%). Multivariate regression analysis found that a diffuse lesion, the lesion and stent length, and the final luminal diameter were predictive for restenosis. Thus, immediate and long-term results of multivessel coronary intervention utilizing stents were improved compared to percutaneous transluminal coronary angioplasty of multivessel lesions. However, there is still need for improvement of long-term results, especially in particular lesion subgroups.

Adult↗

PubMed2004

N-terminal B-type natriuretic peptide predicts extent of coronary artery disease and ischemia in patients with stable angina pectoris.

BACKGROUND: B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are elevated in patients with acute coronary syndromes and are closely linked to prognosis. Because there is only a small amount of data available concerning NT-proBNP in patients with stable angina pectoris, we aimed to determine whether NT-proBNP is of additional diagnostic value in these patients. METHODS AND RESULTS: Ninety-four patients with stable angina pectoris were prospectively included. All patients underwent exercise testing and coronary angiography, and 91 patients received thallium-201 single-photon emission computed tomography myocardial scintigraphy. NT-proBNP was analyzed at rest and after exercise testing. NT-proBNP was elevated in patients with inducible myocardial ischemia shown by single-photon emission computed tomography (396 +/- 80 pg/mL vs 160 +/- 101 pg/mL; P <.01) closely linked to the extent of coronary artery disease (CAD) (no CAD, 148 +/- 29 pg/mL; 1- or 2-vessel disease, 269 +/- 50 pg/mL; 3-vessel disease 624 +/- 186 pg/mL; P <.01). In a multivariate analysis, NT-proBNP was an independent predictor for CAD. The area under the curve of the receiver operating characteristic curve was 0.72 for NT-proBNP to predict CAD. Using an optimized cut off level of 214 pg/mL, CAD can be predicted with high accuracy. The total test efficiency of exercise testing can be improved from 1.46 to 1.52 when combined with NT-proBNP measurement. CONCLUSION: NT-proBNP is elevated in patients with stable angina pectoris and has a close correlation to disease severity. Combining the measurement of NT-proBNP with exercise testing, the test accuracy for predicting severe CAD can be improved. Our data show an incremental value of NT-proBNP in the diagnostic process of stable angina pectoris.

Aged↗

PubMed2004

Decreased pulmonary perfusion in pulmonary vein stenosis after radiofrequency ablation: assessment with dynamic magnetic resonance perfusion imaging.

STUDY OBJECTIVES: The functional impact of pulmonary vein (PV) stenosis on pulmonary perfusion after radiofrequency ablation (RFA) for atrial fibrillation (AF) has not been systematically evaluated previously. Therefore, we correlated magnetic resonance (MR) pulmonary perfusion imaging with single-photon emission CT (SPECT) perfusion and with the degree of PV stenosis (PVS) apparent on MR angiography (MRA) after RF ablation. SETTING: Joint radiology-cardiology collaborative magnetic resonance unit at the Kerckhoff Heart Center. DESIGN AND PATIENTS: This was a cohort study of 110 patients who were routinely examined by MRA after RFA for AF, whereby 51 patients with a PV diameter reduction of > 25% or with clinical symptoms (ie, dyspnea and cough) were enrolled into the study. Patients were examined at follow-up by MR perfusion imaging and MRA, and the results were compared to those from patients who underwent SPECT scanning and from a control group of 26 untreated patients. Twelve patients underwent PVS dilatation as well as 22 sequential follow-up examinations. METHODS: Pulmonary perfusion was evaluated using a dynamic contrast-enhanced three-dimensional MR perfusion sequence (1.5 T, 2.5-s temporal resolution, and 0.05 cm spatial resolution), and high-resolution, contrast-enhanced MRA was performed to measure PV diameter. PV dilatation was performed using an angioplasty catheter that was 8 to 10 mm in diameter. RESULTS: The localization and extent of perfusion defects measured by MRI or SPECT scanning were precisely matched. MR perfusion imaging detected 20 of 21 perfusion defects (sensitivity, 95.2%; specificity, 100%). PVSs and perfusion deficits correlated closely and showed the following threshold: perfusion decreased substantially in PVs 6 mm in diameter. After PVS dilatation, perfusion was restored partially after weeks, and complete normalization was seen in 4 of 12 patients (33%). CONCLUSIONS: PVSs caused severe perfusion deficits, which were reliably demonstrated by MR perfusion imaging. Clinical symptoms correlated better with MR perfusion than they did with MRA. The combination with MRA to assess underlying PVS allowed a "one-stop-shopping" MRI procedure to be carried out. The results led to alterations of RFA techniques, and therefore MRA and MR perfusion imaging may be beneficial in patient follow-up and in evaluating new ablation techniques.

Atrial Fibrillation↗

PubMed2003

Effect of abciximab versus tirofiban on activated clotting time during percutaneous intervention and its relation to clinical outcomes--observations from the TARGET trial.

Previous evidence suggests that the monoclonal antibody abciximab may have a more potent anticoagulant effect than small-molecule glycoprotein (GP) IIb/IIIa inhibitors. We prospectively reviewed collected heparin dose, activated clotting time (ACT), and corresponding clinical outcome data from The Do Tirofiban and ReoPro Give Similar Efficacy Outcome Trial (TARGET), a direct comparison of tirofiban versus abciximab in patients who underwent percutaneous intervention. Of the 4,809 patients enrolled in the trial, 3,739 patients (78%) had an ACT measured after the administration of GP IIb/IIIa and heparin (peak procedural ACT); this formed the population for the present study. Mean total heparin dose was 75 +/- 32 and 76 +/- 31 U/kg in the tirofiban and abciximab groups, respectively. The resultant mean peak ACTs were 296 +/- 91 and 299 +/- 89 seconds (p = 0.09). In a subset of patients with both baseline ACT (before any heparin or GP IIb/IIIa therapy) and peak procedural ACT measurements, the difference in ACT between these time points was 80 +/- 97 vs 82 +/- 101 seconds (p = 0.44) for the tirofiban and abciximab groups, respectively. After adjusting for patients' weight, weight-adjusted heparin dose, and method of ACT measurement in a multiple linear regression analysis, the type of GP IIb/IIIa inhibitor was not predictive of the peak ACT (p = 0.24). When stratified by ACT quartile, no statistically significant difference in bleeding or ischemic end points between the tirofiban and abciximab cohorts was observed. In this large contemporary percutaneous coronary intervention trial, there was no observed difference in the anticoagulant effect of tirofiban and abciximab, as measured by the ACT, or in the incidence of bleeding or ischemic complications in each ACT quartile.

Abciximab↗