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Biomedical subjects

Otmar Pachinger

Publications and source records attributed to Otmar Pachinger.

At least 19 recordsLinked to original sources

Comparison of diagnostic and therapeutic value of transesophageal echocardiography, intravascular ultrasonic imaging, and intraluminal phased-array imaging in aortic dissection with tear in the descending thoracic aorta (type B).

Transesophageal echocardiography (TEE) and conventional intravascular ultrasound (IVUS) have limited capabilities in type B aortic dissection. To evaluate its diagnostic value, intraluminal phased-array imaging (IPAI) was compared with IVUS and TEE. In 23 patients with type B aortic dissection, IPAI was tested with respect to its ability to depict true lumen (TL) and false lumen (FL), to localize which abdominal arteries originate from the TL and FL, and to identify all entries and reentries. After the completion of TEE, 2 additional examiners performed angiography and positioned an AcuNav catheter inside the TL. An IVUS catheter was then introduced into the TL by a fourth examiner. All examiners were blinded to one another. Four additional patients with type B aortic dissection developed peripheral malperfusion due to TL collapse. Transvenous IPAI was used to guide emergency fenestration of the intimal flap. TL and FL could be equally well identified by all diagnostic methods. IPAI detected more entries than IVUS (3.0 +/- 1.2 vs 0.8 +/- 0.5, p <0.001), and thoracic IPAI depicted more entries than TEE (1.8 +/- 1.0 vs 1.2 +/- 0.5, p <0.001). IPAI and IVUS showed >90% of the abdominal side branches. In all patients with peripheral malperfusion, successful emergency intimal flap fenestration was safely guided by IPAI. In conclusion, in the detailed diagnostic evaluation of type B aortic dissection, IPAI is superior to IVUS and TEE in detecting communications between the TL and FL. IPAI is also highly useful as a guiding tool for emergency intimal flap fenestration.

Aortic Dissection↗

Single-beat noninvasive imaging of cardiac electrophysiology of ventricular pre-excitation.

OBJECTIVES: The aim of this study was to determine whether noninvasive imaging of cardiac electrophysiology (NICE) is feasible in patients with Wolff-Parkinson-White (WPW) syndrome in the clinical setting of a catheter laboratory and to test the accuracy of the noninvasively obtained ventricular activation sequences as compared with that of standard invasive electroanatomic mapping. BACKGROUND: NICE of ventricular activation could serve as a useful tool in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. METHODS: NICE works by fusing the data from high-resolution electrocardiographic mapping and a model of the patient's cardiac anatomy obtained by magnetic resonance imaging. The ventricular activation sequence was computed with a bidomain theory-based heart model to solve this inverse problem. Noninvasive imaging of cardiac electrophysiology was performed in 7 patients with WPW syndrome undergoing catheter ablation of the accessory pathway. The position error of NICE was defined as the distance between the site of earliest activation computed by NICE and the successful ablation site identified by electroanatomic mapping (CARTO; Biosense Webster, Diamond Bar, California) for normal atrioventricular (AV) conduction as well as for adenosine-induced AV block. RESULTS: The error introduced by geometric coupling of the CARTO data and the NICE model was 5 +/- 3 mm (model discretization 10 mm). All ventricular accessory pathway insertion sites were identified with an accuracy of 18.7 +/- 5.8 mm (baseline) and 18.7 +/- 6.4 mm (adenosine). CONCLUSIONS: The individual cardiac anatomy model obtained for each patient enables accurate noninvasive electrocardiographic imaging of ventricular pre-excitation in patients with WPW syndrome. Noninvasive imaging of cardiac electrophysiology might be used as a complementary noninvasive approach to localize the origin and help identify and understand the underlying mechanisms of cardiac arrhythmias.

Adult↗

Short term protective effects of iron in a murine model of ischemia/reperfusion.

The role of iron in the pathogenesis of cardio-vascular disorders is still controversial. We studied the effects of iron perturbations on myocardial injury upon temporary ischemia/reperfusion. C57BL/6J male mice were injected with iron dextran for 2 weeks while controls received saline. Mice were then subjected to 30 min of myocardial ischemia and subsequent reperfusion for 6-24 h. Tissue damage was quantified histologically and by troponin T determination. The expressions of tumor necrosis factor-alpha (TNF-alpha), superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) were investigated in non-ischemic and ischemic regions of both groups. After myocardial ischemia and reperfusion, troponin T levels, as a marker of myocardial damage, were significantly reduced in iron-treated mice as compared to control mice (P < 0.05). Under the same conditions the infarction area and damage score were significantly lower in iron-treated animals. In parallel, TNF-alpha and SOD expressions were increased in infarcted regions of iron-treated mice as compared to controls, whereas myocardial iNOS expression was significantly lower in iron-treated mice. Although, iron challenge increased radical formation and TNF-alpha expression in vivo, this did not result in myocardial damage which may be linked to the parallel induction of SOD. Importantly, iron treatment inhibited iNOS expression. Since, an increased nitric oxide (NO) formation has been linked to cardiac damage after acute myocardial infarction, iron may exert short time cardio-protective effects after induction of ischemia/reperfusion via decreasing iNOS formation.

Animals↗

Atherosclerosis as a risk factor for benign prostatic hyperplasia.

OBJECTIVES: To evaluate the relationship between clinical benign prostatic hyperplasia (BPH) and atherosclerosis, using colour Doppler ultrasonography (CDUS) and symptom scores. PATIENTS, SUBJECTS AND METHODS: CDUS was used to evaluate prostatic vascularity in four groups of men, comprising young healthy subjects, patients presenting with coronary artery disease (CAD), diabetes mellitus, or peripheral arterial occlusive disease (PAOD). Resistive index (RI) measurements and computer-assisted quantification of colour pixel density (CPD) were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function were used to quantify symptoms. RESULTS: In diabetic patients and men with PAOD, perfusion of the transition zone (TZ) of the prostate was significantly lower (P < 0.001) and the RI of the TZ was significantly higher (P < 0.001) than in healthy controls and men with CAD. In diabetics and men with PAOD, the mean prostate volume was greater than in healthy controls and men with CAD. The IPSS in patients with vascular damage (diabetes, PAOD) was significantly worse than in the control group. CONCLUSIONS: The significantly lower CPD and higher RI values of the TZ in patients with vascular disease than in healthy subjects support the hypothesis that an age-related impairment of blood supply to the prostate has a key role in the development of BPH.

Aged↗

Risk factors of postoperative nephropathy in patients undergoing innovative CABG and intraoperative graft angiography.

INTRODUCTION: Intraoperative graft angiography is considered gold standard in quality control of innovative CABG techniques. Iodixanol, an iso-osmolar, non-ionic contrast agent has been safely applied in patients with impaired renal function. We aimed to quantify postoperative nephropathy in CABG patients undergoing intraoperative angiography and to define associated risk factors. METHODS: One hundred and thirty-five patients, aged 61 years (range: 43-83), underwent intraoperative angiography following CABG (36 robotically assisted CABG via sternotomy, 41 OPCAB and MIDCAB, 51 AHTECAB, 7 BHTECAB). In all patients iodixanol (Visipaque) was used, median amount: 150 ml (range: 20-500). Nephropathy was defined as an increase in serum creatinine concentration >or= 0.5 mg/dl compared with preoperative values. RESULTS: Nephropathy occured in 19/135 (14%) patients, and was correlated with the following variables: preoperative serum creatinine (p = 0.015, r = 0.208), age (p = 0.008, r = 0.229), postoperative peak troponin T levels (p < 0.001, r = 0.545), postoperative CK-MB peak levels (p = 0.028, r = 0.189), and presence of peripheral vascular disease (p = 0.011). No correlation was found for the contrast agent amount, diabetes mellitus, hypertension, preoperative urea level, cardiopulmonary bypass time, aortic cross clamp time, postoperative CK peak levels. Multivariate analysis showed that postoperative peak troponin T levels (p < 0.001), preoperative serum creatinine (p = 0.031), and patient age (p = 0.043) were independently associated with a postoperative increase of serum creatinine. In all 19 patients with postoperative nephropathy serum creatinine levels returned to preoperative levels. CONCLUSION: Patients with older age and elevated serum creatinine levels undergoing innovative CABG and intraoperative angiography were at increased risk of postoperative nephropathy. However, no correlation was found between the amount of contrast agent (iodixanol) applied and the nephropathy rate and none of the nephropathy cases persisted.

Adult↗

Comparison of three-dimensional imaging to transesophageal echocardiography for preoperative evaluation in mitral valve prolapse.

Transesophageal echocardiography (TEE) is not optimally suited for recognizing which valve segments are involved in type II mitral valve dysfunction. This study was conducted to compare the diagnostic value of TEE and 3-dimensional image reconstruction (3DIR) in the assessment of Carpentier type II mitral valve lesions. In 74 patients (mean age 59+/-13 years) with mitral regurgitation due to type II valve dysfunction, TEE and 3DIR were performed and analyzed by 2 experts before surgical repair. Leaflet scallops and commissures were displayed in short-axis en face and long-axis views. Echocardiographic results were surgically validated. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated, broken down by valve segments and Barlow's disease. Interobserver variability was also determined. Compared with TEE, 3DIR was superior with respect to sensitivity, positive and negative predictive values, and accuracy, although not always significantly (p<0.05). Specificity was higher for P2 lesions. The clearest advantage of 3DIR over TEE was higher sensitivity in commissural and bileaflet defects (p<0.05). Interobserver agreement on 3DIR was stronger than on TEE results (kappa values 0.52 vs 0.82, p<0.0001). There were 16 disagreements (23%) on TEE but only 5 (7%) on 3DIR readings. In conclusion, the more complex the lesion, the more valuable 3DIR is compared with TEE. Before repair, 3DIR is beneficial for the evaluation and classification of the specific pathology in type II mitral valve dysfunction.

Adult↗

Short-term improvement in submaximal exercise capacity by optimized therapy with ACE inhibitors and beta blockers in heart failure patients is associated with restoration of peripheral endothelial function.

BACKGROUND: Improved exercise capacity in chronic heart failure (CHF) has been attributed to restoration of endothelial function. ACE inhibitors as well as beta blockers have previously been shown to enhance endothelial function and exercise capacity. The aim of this study was to determine whether short-term improvement in submaximal exercise capacity induced by optimized therapy with ACE inhibitors in combination with beta blockers is associated with restoration of endothelial function in CHF patients. METHODS: Thirty-three patients with CHF were evaluated: six-minute walk test, NYHA class, brain natriuretic peptide (BNP), big Endothelin-1 (bigET-1) and flow-mediated vasodilation (FMD) of the brachial artery were assessed at baseline and after a 3-month period of optimized neurohormonal therapy. Two groups were formed retrospectively based on the changes in submaximal exercise capacity (responders and non-responders). RESULTS: Optimization of neurohormonal therapy was comparable between groups. Responders (n=17) revealed a significant increase in walking distance (304+/-109 to 441+/-75 m; p<0.01), which was paralleled by a decrease in NYHA class (2.7+/-0.6 to 2.0+/-0.4; p<0.01), BNP (484+/-454 to 243+/-197 pg/ml; p<0.01), and bigET-1 (2.0+/-0.9 vs. 1.5+/-0.6 fmol/ml; p=0.04). By contrast, the latter variables did not change in non-responders. Improvement in functional capacity in responders was associated with an increase in FMD (8.2+/-3.9% to 11.0+/-5.6%; p<0.05). Increments in FMD were directly correlated with increases in walking distance (r=0.34; p<0.05). CONCLUSION: Short-term improvement of submaximal exercise capacity in CHF patients following optimized therapy with ACE inhibitors and beta blockers is associated with restoration of endothelial function in conduit arteries.

Adrenergic beta-Antagonists↗

Multislice computed tomography for detection of patients with aortic valve stenosis and quantification of severity.

OBJECTIVES: The purpose of this study was to evaluate whether multislice computed tomography (MSCT) provides a reliable, noninvasive imaging modality for identification of patients with degenerative aortic valve stenosis (AS) by quantifying the aortic valve area (AVA) in comparison to the accepted diagnostic standard transthoracic echocardiography (TTE). BACKGROUND: Management of patients with degenerative AS is based on the severity of disease. The severity of AS in clinical practice is assessed by TTE and classified as mild, moderate, or severe according to the AVA. METHODS: Forty-six patients were examined with contrast-enhanced, electrocardiogram-gated, 16-row MSCT for the evaluation of the diagnostic accuracy. In 30 patients, quantification of the AVA with MSCT was compared to TTE using the continuity equation with Doppler velocity-time integral for calculation of the AVA. RESULTS: Sensitivity of MSCT for the identification of patients with degenerative AS was 100%, and the specificity was 93.7%. Thirty of 46 patients had AS determined by TTE. Quantification of AVA by MSCT (mean AVA = 0.94 cm2) in patients with AS showed a good correlation to TTE (r = 0.89; p < 0.001). Bland-Altman plot illustrated good intermodality agreement between the two methods (limits of agreement, 0.20; 0.29). CONCLUSIONS: Multislice computed tomography may provide an accurate, noninvasive imaging technique for detection of patients with AS and quantification of AVA.

Aged↗

Reduction of soluble P-selectin by statins is inversely correlated with the progression of coronary artery disease.

BACKGROUND: Cell adhesion molecules (CAM) play an important role in the pathogenesis of atherosclerosis by mediating the binding of leukocytes to the endothelium. Soluble CAM isoforms are known to be elevated in the sera of patients suffering from coronary artery disease (CAD). METHODS: We measured the concentrations of soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, P-selectin, platelet endothelial cell adhesion molecule-1, and highly sensitive C-reactive protein (hs-CRP) in the blood of 47 CAD patients before and 6 months after starting statin therapy and in 16 untreated CAD patients. The progression of CAD was monitored by calculating the coronary calcium score using electron beam computed tomography. RESULTS: Soluble P-selectin (92+/-11 ng/ml vs. 59 +/- 4 ng/ml, p < 0.0001) and hs-CRP (0.92 +/- 0.14 mg/dl vs. 0.42 +/- 0.11 mg/dl, p < 0.001) decreased significantly in the statin-treated group compared to baseline levels. None of the other proteins studied showed significant changes. In contrast to hs-CRP, the reduction of soluble P-selectin concentrations correlated directly with the lowering of total cholesterol (r(2) = 0.236, p < 0.005) and inversely with the progression of CAD (r(2) = 0.393, p < 0.0001). CONCLUSIONS: Our results suggest P-selectin as an additional marker for the beneficial action of statins in patients with CAD.

Analysis of Variance↗

Valvular heart disease in Parkinson's disease vs. controls: An echocardiographic study.

Restrictive valvulopathy has been reported in association with dopamine agonist therapy in parkinsonian patients. The majority of reports have been related to pergolide, but anecdotal cases following treatment with bromocriptine or cabergoline have also been presented. It is presently unclear whether the potential induction of restrictive cardiac valvulopathy is a class effect of all dopamine agonists or if there is a differential risk between ergot and nonergot compounds. In this study, the frequency of a valvular regurgitation as assessed by routine transthoracic echocardiography was compared between 75 patients with Parkinson's disease (PD) treated with pergolide (n = 29), cabergoline (n = 13), pramipexole or ropinirole (n = 33), and 49 age-matched nonparkinsonian controls. The exposure to pergolide and cabergoline was associated with higher frequencies of valvular regurgitation grades 2 and 3 (31% and 47%) compared with age-matched controls (13%), while there was no increase of valvular regurgitation grades 2 and 3 in patients treated with nonergot compounds (10%). Evidence for restrictive valvulopathy was found in one patient treated with pergolide and cabergoline each. While this study shows similarly increased frequencies of valvular regurgitation in patients treated with the ergot agonists pergolide and cabergoline in comparison to both normal controls and patients treated with nonergot agonists, evidence for restrictive valvulopathy was only found in two cases. These results highlight the need for further prospective studies of the prevalence and underlying mechanisms of cardiac valvulopathy in PD patients treated with different dopamine agonists.

Aged↗

Interventional and medical treatment of acute heart failure due to inflammation: four cases.

Four patients (aged 15-41 years, mean age 26.7 years) with fulminant myocarditis undergoing mechanical circulatory support are reported. All patients suffered from acute low-output syndrome refractory to inotropic support. Diagnosis was confirmed by histology and immunohistochemistry. RT-PCR (reverse transcription-polymerase chain reaction) from endomyocardial biopsy specimens revealed parvovirus B19 in two patients and a coinfection with Chlamydia pneumoniae and parvovirus B19 in one patient. Midterm support with the biventricular Thoratec system was preceded by implantation of an extracorporeal membrane oxygenation (ECMO) device in two patients. Two patients regained full cardiac function and were successfully weaned from the ventricular assist device (VAD) after 12 and 40 days. Heart transplantation was performed in another patient without evidence of myocardial recovery after 53 days. One patient died of cerebral hemorrhage on day 12 after VAD implantation. In summary, patients with life-threatening fulminant myocarditis can be successfully bridged to recovery or transplantation with mechanical circulatory support.

Adolescent↗

Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study.

BACKGROUND: Coronary atherosclerosis includes an activation of circulating T lymphocytes. Statins exert anti-inflammatory effects beyond lipid lowering. Whether these properties influence systemic T lymphocytes is unclear. METHODS: To investigate the effect of atorvastatin on circulating T-lymphocyte subsets producing proinflammatory and anti-inflammatory cytokines (interferon gamma [IFN-gamma(+)], interleukin 2 [IL-2(+)], IL-4(+), and IL-10(+)) and on the T-cell-activating soluble CD40 ligand (sCD40L), 30 hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. Eight healthy volunteers served as controls. Levels of peripheral cytokine-producing CD4+ and CD8+ T cells and their CD28- subsets were determined by FACS. Serum soluble CD40L was measured with ELISA. RESULTS: IL-2(+) T lymphocytes and sCD40L levels were higher in patients with CAD compared with controls, whereas IFN-gamma(+) and anti-inflammatory IL-4(+) and IL-10(+) T lymphocytes were similar. Levels of IL-2(+), IFN-gamma(+), IL-4(+), and IL-10(+) T-cell subsets as well as CD28- T lymphocytes were neither changed by atorvastatin nor by placebo, whereas sCD40L was lowered only in atorvastatin-treated patients (P < .01). CONCLUSION: Circulating IL-2(+) T lymphocytes are increased in patients with stable CAD reflecting an activation of the global immune system, but are not influenced by atorvastatin therapy. The elevated levels of platelet-derived T-lymphocyte-stimulating sCD40L are decreased by atorvastatin probably reflecting an atheroprotective effect. Hence, sCD40L may be an additional biomarker to be considered when evaluating the treatment effects of statins in patients with stable CAD.

Atorvastatin↗

Aortic valve calcification as quantified with multislice computed tomography predicts short-term clinical outcome in patients with asymptomatic aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Aortic valve calcification may be an independent risk factor for adverse clinical outcome. The study aim was to assess the predictive value of possible risk factors, including the severity of aortic valve calcification as quantified with 16-multislice computed tomography (MSCT) for adverse short-term clinical outcome in patients with asymptomatic, degenerative aortic stenosis (AS). METHODS: Possible risk factors for adverse short-term clinical outcome were prospectively tested in 34 consecutive patients with asymptomatic AS as follows: (i) aortic valve calcium (AVC) score as quantified with MSCT; (ii) echocardiographic parameters--aortic valve area (AVA) calculated with continuity equation, mean and maximal transvalvular pressure gradients, end-diastolic septal wall diameter; and (iii) laboratory tests (brain natriuretic peptide (BNP), C-reactive protein (CRP)). RESULTS: Within 18-24 months of follow up, 11 of 34 patients developed a major adverse clinical outcome. Ten patients suffered from onset of symptoms accompanied by hemodynamic progression, and one patient died from sudden cardiac death. Six of these 10 patients underwent aortic valve replacement, one patient declined surgery, and three patients were not accepted for surgery (one of these died suddenly shortly afterwards). The aortic valve calcium score was the strongest predictor of a major adverse clinical event (p < 0.001) among all parameters assessed (1,928 +/- 789 versus 5,111 +/- 2,409 Agatston units). The plasma level of BNP (p = 0.003), mean transvalvular pressure gradient (p = 0.002) and AVA (p = 0.003) were also risk factors for adverse clinical outcome. CONCLUSION: The AVC score as quantified with MSCT predicted adverse short-term clinical outcome in patients with asymptomatic AS. In patients with severe aortic valve calcification, close follow up examinations are mandatory, and early elective surgery may be considered even in the absence of symptoms. MSCT provides a comprehensive non-invasive imaging approach for risk stratification in patients with asymptomatic AS.

Aortic Valve↗

Countervailing effects of rapamycin (sirolimus) on nuclear factor-kappa B activities in neointimal and medial smooth muscle cells.

OBJECTIVE: Local application of rapamycin (sirolimus) by drug-eluting stents prevents lumen obliteration after angioplasty by inhibition of neointimal hyperplasia. The effects of rapamycin on neointimal smooth muscle cells (niSMC) which are responsible for the occurrence of restenosis have not been investigated so far. METHODS AND RESULTS: Rat niSMC and medial SMC (mSMC) were obtained from balloon catheter-injured arteries. The niSMC exhibited higher basal NF-kappaB activity and TNF-alpha mRNA levels. Nuclear protein binding to NF-kappaB-DNA was attenuated in niSMC by incubation with rapamycin (0.1 and 1 microg/ml) for 24 and 48 h. In contrast in mSMC, 0.1 microg/ml rapamycin had no effect and at 1 microg/ml even increased nuclear protein binding to NF-kappaB-DNA. After 12 h incubation, rapamycin (0.001-10 microg/ml) induced IkappaB-alpha protein in niSMC, whereas in mSMC it stimulated IkappaB-alpha at much lower levels. Prolonged rapamycin treatment (1 microg/ml for 72 h) had no effect on TNF-alpha mRNA level and NF-kappaB activity in niSMC, whereas it led to their increase in mSMC. Vascular endothelial growth factor (VEGF) secretion was higher in mSMC than in niSMC; rapamycin decreased VEGF levels in both cell types. Ultrastructural analysis suggested that rapamycin caused early signs of degeneration in niSMC, but enhanced protein synthesis in mSMC. CONCLUSIONS: This study shows that rapamycin influences the inflammatory phenotypes of SMC in opposite directions: it reduces the high basal NF-kappaB activity in niSMC and enhances NF-kappaB activity and TNF-alpha expression in mSMC. In addition, rapamycin inhibits VEGF production regardless of the phenotype of SMC. These findings shed light on molecular mechanisms and structural changes underlying therapeutic applications of rapamycin in prevention of restenosis, inhibition of chronic transplant arteriosclerosis and reduction of secondary malignoma formation due to immunosuppression.

Animals↗

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.

Adult↗