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ABSTRACT: To investigate whether proton pump inhibitors (PPIs) negatively affect clinical outcome in patients treated with clopidogrel. Systematic review and meta-analysis. Outcomes evaluated were combined major adverse cardiac events (MACE), myocardial infarction (MI), stent thrombosis, death and gastrointestinal bleeding. Studies included were randomized trials or post-hoc analyzes of randomized trials and observational studies reporting adjusted effect estimates. Twenty five studies met the selection criteria and included 159 138 patients. Administration of PPIs together with clopidogrel corresponded to a 29% increased risk of combined major cardiovascular events [risk ratio (RR) = 1.29, 95% confidence intervals (CI) = 1.15-1.45] and a 31% increased risk of MI (RR = 1.31, 95%CI = 1.12-1.53). In contrast, PPI use did not negatively influence the mortality (RR = 1.04, 95%CI = 0.93-1.16), whereas the risk of developing a gastrointestinal bleed under PPI treatment decreased by 50% (RR = 0.50, 95% CI = 0.37-0.69). The presence of significant heterogeneity might indicate that the evidence is biased, confounded or inconsistent. The sensitivity analysis, however, yielded that the direction of the effect remained unchanged irrespective of the publication type, study quality, study size or risk of developing an event. Two studies indicate that PPIs have a negative effect irrespective of clopidogrel exposure. In conclusion, concomitant PPI use might be associated with an increased risk of cardiovascular events but does not influence the risk of death. Prospective randomized trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel treated patients as the PPI-clopidogrel drug-drug interaction does not seem to be a class effect.
Journal of Thrombosis and Haemostasis 12/2010; 8(12):2624-41. · 5.73 Impact Factor
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ABSTRACT: The prognostic value of the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and multiple electrode aggregometry (MEA) for thrombotic adverse events has been shown in independent studies. As no direct comparison between the two methods has been made so far, we investigated which laboratory approach has a better predictive value for stent thrombosis.
The VASP phosphorylation assay and MEA were performed in 416 patients with coronary artery disease undergoing percutaneous coronary intervention. The rate of stent thrombosis was recorded during a 6-month follow-up.
Definite stent thrombosis occurred in three patients (0.7%) and probable stent thrombosis in four (1%). Receiver operating characteristic (ROC) analysis demonstrated that MEA distinguishes between patients with or without subsequent stent thrombosis better than the VASP phosphorylation assay: the area under the ROC curve was higher for MEA (0.92; P=0.012) than for the VASP phosphorylation assay (0.60; P=0.55). At equal levels of sensitivity (100%), the specificity was greater for MEA than for the VASP phosphorylation assay (86% vs. 37%). Stent thrombosis occurred in 9% of patients with platelet hyperreactivity in MEA, who were simultaneously clopidogrel non-responders in the VASP phosphorylation assay. Interestingly, clopidogrel non-responders in the VASP phosphorylation assay without platelet hyperreactivity in MEA did not suffer from stent thrombosis.
Platelet hyperreactivity in MEA might be a better risk predictor for stent thrombosis than the assessment of the specific clopidogrel effect with the VASP phosphorylation assay.
Journal of Thrombosis and Haemostasis 11/2009; 8(2):351-9. · 5.73 Impact Factor
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ABSTRACT: We tested the hypothesis that plasma levels of plasminogen activator inhibitor-1 (PAI-1) are influenced by percutaneous coronary intervention (PCI) with the implantation of drug eluting stents (DES) and are able to predict the occurrence of in-stent restenosis (ISR).
PAI-1 active antigen plasma levels were determined in 75 patients before and 24 h after PCI with DES implantation. Patients with ISR after six to eight months (16%) showed significantly lower PAI-1 plasma levels before PCI (ISR, 11.7 +/- 8.1 ng mL(-1); non-ISR, 22.8 +/- 18.8 ng mL(-1); P <0.05). PAI-1 levels in the lowest tertile were associated with a 9.5-fold increased risk of ISR, independent of clinical risk factors, angiographic or procedural characteristics, compared to the highest tertile (P < 0.05). The induced change of PAI-1 active antigen 24 h after PCI was significantly higher in patients with ISR (ISR, +5.6 +/- 8.0 ng mL(-1); non-ISR, -3.2 +/- 12.1 ng mL(-1); P < 0.05) with positive correlation to late lumen loss (r = 0.30; P < 0.05).
ISR after DES implantation is significantly related to plasma levels of PAI-1 active antigen before and after PCI. If confirmed by larger multicenter studies, the determination of PAI-1 plasma levels might be clinically helpful in the identification of patients at high risk of developing of ISR, even after DES implantation.
Journal of Thrombosis and Haemostasis 03/2008; 6(3):508-13. · 5.73 Impact Factor
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P Mad,
H Domanovits,
C Fazelnia,
K Stiassny,
G Russmüller,
A Cseh,
G Sodeck,
T Binder, G Christ,
T Szekeres,
A Laggner,
H Herkner
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ABSTRACT: At very early stages of acute myocardial infarction (AMI), highly sensitive biomarkers are still lacking.
To evaluate the utility of human heart-type fatty acid-binding protein (h-FABP) for early diagnosis of AMI.
Prospective diagnostic study.
Consecutive patients presenting to the emergency department with chest pain or dyspnoea within 24 h of symptom onset were included. At presentation, the h-FABP test result was compared to the standard diagnostic work-up, including repeated ECG and troponin T measurements. Sensitivity analysis was performed for inconclusive tests.
We enrolled 280 patients presenting to hospital with a median symptom onset of 3 h (IQR 2-6 h): 109 (39%) had AMI. At presentation, h-FABP had a sensitivity of 69% (95%CI 59-77) and specificity of 74% (95%CI 66-80); 45 tests were false-positive and 34 were false-negative. Omitting inconclusive tests increased sensitivity and specificity only slightly. AMI was identified significantly earlier by h-FABP than by troponin T (24 vs. 8 patients, p=0.005).
Although h-FABP can help to detect myocardial damage at an early stage in patients with chest pain or dyspnoea, it appears unsuitable as a stand-alone test for ruling out AMI.
QJM: monthly journal of the Association of Physicians 05/2007; 100(4):203-10. · 2.33 Impact Factor
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ABSTRACT: The plasmin activation system is involved in the development of restenosis after percutaneous coronary interventions (PCI). Conflicting data exist concerning the role of plasminogen activator inhibitor-1 (PAI-1) and its predictive value for restenosis.
To evaluate the fibrinolytic response to injury after PCI with or without stent implantation on different antithrombotic medications and its relation to late restenosis.
Eighty consecutive patients with successful PCI without (balloon only; n = 37) or with stent implantation (stent; n = 43) on different antithrombotic regimes (balloon only, aspirin; stent, aspirin/coumadin/dipyridamole vs. aspirin/ticlopidine). Blood samples were taken at baseline and up to 7 days after PCI and PAI-1 active antigen and tissue plasminogen activator (t-PA) antigen were determined. Restenosis was angiographically determined after 6 months.
PCI increased both t-PA and PAI-1 levels (P < 0.001), with a significant prolonged and pronounced increase in stent vs. balloon-only patients (P < 0.05). Restenosis (stent 26%; balloon 38%) was significantly correlated to an attenuated PAI-1 increase after 24 h in the ticlopidine group (P = 0.007; restenosis, relative Delta PAI-1 + 50 +/- 28%; non-restenosis, + 139 +/- 50%), but not in the coumadin group. In the balloon-only group late restenosis (ISR) was associated with a trend for an augmented PAI-1 increase after 24 h.
Coronary stent implantation significantly increases t-PA and PAI-1 plasma levels up to 1 week compared with balloon angioplasty alone. ISR in ticlopidine-treated patients was associated with an attenuated early PAI-1 active antigen increase. A less than 50% increase 24 h after stent implantation under ticlopidine treatment may identify patients at risk for the development of ISR.
Journal of Thrombosis and Haemostasis 03/2005; 3(2):233-9. · 5.73 Impact Factor
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ABSTRACT: Zusammenfassung: Der Nutzen einer Operation bei noch symptomfreier höhergradiger Aortenstenose wird nach wie vor kontroversiell beurteilt. Wir berichten unsere kürzlich im New England Journal of Medicine publizierten Daten zum natürlichen Verlauf dieser Erkrankung und möglichen Prognosefaktoren. 128 konsekutive, asymptomatische Patienten mit höhergradiger Aortenstenose (Alter 60 ± 18 Jahre, maximale Aortenflußgeschwindigkeit 5,0 ± 0,6 m/s), die im Laufe des Jahres 1994 untersucht wurden, wurden anschließend prospektiv bis 1998 weiter beobachtet. Bei einem mittleren Beobachtungszeitraum von 22 ± 18 Monaten war das ereignisfreie Überleben mit den definierten Endpunkten Tod oder Klappenoperation wegen der Entwicklung von Beschwerden nach einem Jahr 67 ± 5 %, nach 2 Jahren 56 ± 5 % und nach 4 Jahren 33 ± 5 %. 8 Patienten verstarben, davon 6 an kardialer Ursache und 59 Patienten wurden operiert. Die multivariate Analyse zeigte, dass lediglich das Ausmaß der Klappenverkalkung ein unabhängiger Prognosefaktor war, nicht aber das Alter, das Geschlecht oder das Vorhandensein von koronarer Herzkrankheit, Hypertonie, Diabetes mellitus oder Hypercholesterinämie. Bei Patienten mit nicht oder nur leicht verkalkter Aortenklappe betrugen die ereignisfreien Überlebensraten 92 ± 5 % nach einem, 84 ± 8 % nach zwei und 75 ± 9 % nach 4 Jahren. Im Vergleich dazu hatten die Patienten mit mittel- oder höhergradiger Verkalkung der Aortenklappe ein ereignisfreies Überleben von 60 ± 6 % nach einem, 47 ± 6 % nach zwei und 20 ± 5 % nach vier Jahren. Eine Hochrisikogruppe stellten jene Patienten dar, die eine mittel- oder höhergradig verkalkte Aortenklappe hatten und bei denen zusätzlich ein Anstieg der Aortenflussgeschwindigkeit von über 0,3 m /s innerhalb eines Jahres beobachtet wurde. Innerhalb von 2 Jahren ab dieser Beobachtung wurden 79 % dieser Patienten entweder wegen der Entwicklung von Beschwerden operiert oder sie verstarben. Zusammenfassend erscheint eine mittel- oder höhergradige Klappenverkalkung zusammen mit der Beobachtung einer raschen hämodynamischen Progression eine Hochrisikogruppe von Patienten mit schwerer, noch symptomfreier Aortenstenose zu identifizieren, bei der ein elektiver Klappenersatz in Betracht gezogen werden sollte, anstatt die Entwicklung von Beschwerden abzuwarten.Identification of High Risk Patients with Severe but Asymptomatic Aortic StenosisSummary: Whether asymptomatic patients with severe aortic stenosis benefit from surgery remains unclear. We report our data recently published in the New England Journal of Medicine on the natural history of this disease and predictors of outcome. 128 consecutive, asymptomatic patients with severe aortic stenosis (age 60 ± 18 years, peak aortic jet velocity 5.0 ± 0.6 m/s), were prospectively followed from 1994 until 1998. During a mean follow-up duration of 22 ± 18 months, event-free survival, with end points defined as death or valve replacement necessitated by the development of symptoms was 67 ± 5 % at one year, 56 ± 5 % at two years, and 33 ± 5 % at 4 years. There were 8 deaths (6 cardiac) and 59 underwent valve replacement. By multivariate analysis, only the extent of aortic-valve calcification was an independent predictor of outcome, but not age, sex, and the presence of coronary artery disease, hypertension, diabetes, and hypercholesterolemia. Event-free survival for patients with no or mild calcification of the aortic valve was 92 ± 5 % at one year, 84 ± 8 % at two years, and 75 ± 9 % at 4 years. In contrast, patients with moderate or severe calcification had an event-free survival of only 60 ± 6 %, 47 ± 6 %, and 20 ± 5 % at 1, 2, and 4 years, respectively. Patients with moderate or severe valve calcification and an increase in aortic jet velocity > 0.3 m/s within one year represented a high-risk group: 79 % of these patients underwent surgery or died within two years of the observed increase. In conclusion, moderate to severe aortic valve calcification and the observation of rapid hemodynamic progression identifies a high risk group of patients with asymptomatic severe aortic stenosis in which early elective surgery should be considered rather than have surgery delayed until symptoms develop.
Acta Medica Austriaca 12/2001; 28(1):27 - 29.
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ABSTRACT: BACKGROUND AND AIM: Atherosclerosis and its clinical sequelae are responsible for the highest death rate in industrialized countries. Seroepidemiological, pathological and immunohistochemical studies have suggested a relation between Chlamydia pneumoniae infection and the development of coronary sclerosis. Aim of this study was to investigate the frequency distribution of Chlamydia pneumoniae antibody titers in patients with different clinical stages of coronary artery disease (CAD) and patients without CAD as well as a possible age dependence of antibody titers within the study groups. For this purpose, 522 consecutive patients of a cardiology ward were investigated, over a period of 10 months, for the presence of Chlamydia pneumoniae antibodies (IgG, IgA, IgM) using specific ELISA's. In general, there was no difference in the frequency of positive Chlamydia antibody titers between CAD patients and the control group. Only in the subgroup of unstable CAD-patients < 50 years a tendency of increased antibody titers was present. Patients with stable angina, unstable angina, or acute myocardial infarction exhibited no significant differences in the rate of infection between the different age groups (p < 0.117). In contrast, there was a significant increase in positive Chlamydia pneumoniae antibodies with increasing age in the control group (p = 0.002). The relatively high incidence of positive Chlamydia pneumoniae antibody titers in young CAD patients, which is associated with a loss of age-dependent increase of the antibody titers in the CAD group, might indicate a specific role of Chlamydia pneumoniae infections for the manifestation of premature CAD (before the age of 50). Due to the increased rate of Chlamydia pneumoniae infections with increasing age, the determination of Chlamydia pneumoniae antibody titers does not allow reliable conclusions on the infectious pathogenesis of CAD. Furthermore, our unability to demonstrate differences in antibody titers between CAD patients with stable angina, unstable angina, and acute myocardial infarction suggests that acute Chlamydia pneumoniae infections are not responsible for the development of acute coronary syndromes.
Wiener klinische Wochenschrift 10/2001; 113(19):727-30. · 0.81 Impact Factor
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ABSTRACT: Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the plasmin- and thrombin activation system are associated with the predominate affection of females. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standardized venous occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p = 0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity, higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p = 0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We hypothesize, that the observed presence of gender differences in the plasmin- and thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic state might, in part, explain the female predominant incidence of this disease.
Thrombosis and Haemostasis 09/2001; 86(2):557-62. · 5.04 Impact Factor
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ABSTRACT: Whether asymptomatic patients with severe aortic stenosis benefit from surgery remains unclear. We report our data recently published in the New England Journal of Medicine on the natural history of this disease and predictors of outcome.
Acta Medica Austriaca 02/2001; 28(1):27-9.
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ABSTRACT: Whether to perform valve replacement in patients with asymptomatic but severe aortic stenosis is controversial. Therefore, we studied the natural history of this condition to identify predictors of outcome.
During 1994, we identified 128 consecutive patients with asymptomatic, severe aortic stenosis (59 women and 69 men; mean [+/-SD] age, 60+/-18 years; aortic-jet velocity, 5.0+/-0.6 m per second). The patients were prospectively followed until 1998.
Follow-up information was available for 126 patients (98 percent) for a mean of 22+/-18 months. Event-free survival, with the end point defined as death (8 patients) or valve replacement necessitated by the development of symptoms (59 patients), was 67+/-5 percent at one year, 56+/-5 percent at two years, and 33+/-5 percent at four years. Five of the six deaths from cardiac disease were preceded by symptoms. According to multivariate analysis, only the extent of aortic-valve calcification was an independent predictor of outcome, whereas age, sex, and the presence or absence of coronary artery disease, hypertension, diabetes, and hypercholesterolemia were not. Event-free survival for patients with no or mild valvular calcification was 92+/-5 percent at one year, 84+/-8 percent at two years, and 75+/-9 percent at four years, as compared with 60+/-6 percent, 47+/-6 percent, and 20+/-5 percent, respectively, for those with moderate or severe calcification. The rate of progression of stenosis, as reflected by the aortic-jet velocity, was significantly higher in patients who had cardiac events (0.45+/-0.38 m per second per year) than those who did not have cardiac events (0.14+/-0.18 m per second per year, P<0.001), and the rate of progression of stenosis provided useful prognostic information. Of the patients with moderately or severely calcified aortic valves whose aortic-jet velocity increased by 0.3 m per second or more within one year, 79 percent underwent surgery or died within two years of the observed increase.
In asymptomatic patients with aortic stenosis, it appears to be relatively safe to delay surgery until symptoms develop. However, outcomes vary widely. The presence of moderate or severe valvular calcification, together with a rapid increase in aortic-jet velocity, identifies patients with a very poor prognosis. These patients should be considered for early valve replacement rather than have surgery delayed until symptoms develop.
New England Journal of Medicine 08/2000; 343(9):611-7. · 53.30 Impact Factor
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M Zehetgruber,
D Mörtl,
G Porenta,
G Mundigler, G Christ,
R Lengauer,
G Stix,
P Probst,
G Maurer,
H Sochor,
P Siostrzonek
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ABSTRACT: Recent studies demonstrate the feasibility of coronary flow reserve measurements by transesophageal echocardiographic (TEE) Doppler recordings of coronary sinus or left anterior descending (LAD) coronary artery flow velocity for detecting stenoses of the LAD artery. This study compares coronary flow reserve measurements by Doppler TEE with thallium-201 (201Tl) single-photon emission computed tomography (SPECT) in patients with proximal single-vessel LAD stenosis.
Nineteen patients with various degrees of LAD stenosis (mean area stenosis 71 +/- 24%; range 24-96%) were studied. Area stenosis by quantitative coronary angiography was < 75% in 7 patients and > 75% in 12 patients. Transesophageal LAD and coronary sinus Doppler measurements were performed at baseline and after intravenous dipyridamole. Coronary flow reserve was calculated as the ratio of hyperemic to baseline average peak velocities. Predefined coronary flow reserve cut-off values of 1.8 for the coronary sinus method and of 2.0 for the LAD method were used for diagnosis of significant LAD stenosis. Results were compared with qualitative 201Tl dipyridamole SPECT.
Overall predictive accuracy for diagnosis of > 75% LAD stenosis was 79% for 201Tl SPECT, 77% for the transesophageal LAD and 79% for the transesophageal coronary sinus technique. Concordant results between 201Tl SPECT and the LAD and coronary sinus Doppler methods were observed in 79% and 71% of patients, respectively.
Thallium-201 SPECT and transesophageal Doppler assessment of coronary flow reserve have similar accuracy for diagnosing significant proximal LAD stenosis. Therefore, both transesophageal Doppler techniques might constitute another widely available, noninvasive method for assessment of left coronary artery disease, if disease location is proximal.
Clinical Cardiology 05/1998; 21(4):247-52. · 2.15 Impact Factor
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ABSTRACT: The effects of the selective alpha-1-adrenoceptor antagonist doxazosin on metabolic and fibrinolytic parameters were studied in hypertensive patients with various degrees of fasting plasma insulin levels (Group A: 22.5 +/- 3 microU/ml, Group B: 8.1 +/- 1.5 microU/ml; p <0.01) to disclose a potential link between a doxazosin-induced alteration of insulin and/or lipid metabolism and possible changes of these parameters on the fibrinolytic system. Doxazosin treatment resulted in a dose-dependent reduction of basal insulin levels in group A to 16 +/- 3 microU/ml; p <0.05. This finding was paralleled by a dose-dependent increase in t-PAmass concentration in the same patient group (basal t-PAmass from 9.7 +/- 1 to 15.5 +/- 2 ng/ml; p <0.05). As PAI-1 "active" as well as total antigen levels were not altered in parallel, the net effect on the endogenous fibrinolytic system is an increase of the fibrinolytic potential.
Thrombosis and Haemostasis 02/1998; 79(2):378-82. · 5.04 Impact Factor
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M Zehetgruber,
G Mundigler, G Christ,
C Merhaut,
U Klaar,
C Kratochwill,
T Neunteufl,
S Hofmann,
G Heinz,
G Maurer,
P Siostrzonek
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ABSTRACT: Recent studies suggest prophylactic intraaortic balloon-pulsation (IABP) in patients undergoing coronary reperfusion therapy. However, variable effects of IABP on coronary blood flow are reported. It is suggested that augmentation of coronary flow is more effective in patients with a compromised hemodynamic status, which might have potential relevance in selecting IABP treatment in patients undergoing reperfusion therapy.
The American Journal of Cardiology 11/1997; 80(7):951-5. · 3.37 Impact Factor
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ABSTRACT: The present study was performed to compare coronary flow reserve by transesophageal Doppler echocardiography and intracoronary Doppler flow wire measurements in patients with LAD disease.
17 patients with various degree of LAD stenosis were studied. Intracoronary LAD Doppler measurements were performed at baseline and after intracoronary injection of 18 micrograms adenosine. Transesophageal coronary sinus and LAD Doppler measurements were performed at baseline and after intravenous dipyridamole (0.6 mg/kg/5 min). Coronary flow reserve was calculated as the ratio of hyperemic to baseline average peak velocities.
Coronary flow reserve was 2.44 +/- 0.62 and 2.19 +/- 0.76 for proximal and distal intracoronary measurements and was 2.25 +/- 0.64 and 1.74 +/- 0.63 for transesophageal LAD- and coronary sinus measurements. Proximal intracoronary flow reserve significantly correlated with transesophageal coronary sinus (r = 0.73, p < or = 0.001) and LAD (r = 0.70, p < or = 0.005) measurements, whereas distal intracoronary flow reserve only correlated with transesophageal coronary sinus flow reserve (r = 0.56, p < or = 0.02). Receiver operating characteristic curve analysis demonstrated similar diagnostic accuracy of all applied techniques for detection of a significant LAD stenosis.
Coronary flow reserve by both transesophageal techniques correlated with intracoronary Doppler flow wire measurements, however considerable discrepancies may occur in the individual patient.
Cardiovascular Research 10/1997; 36(1):21-7. · 6.06 Impact Factor
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ABSTRACT: The longterm effects of ketamine on haemodynamic parameters and exogenous catecholamine requirements were studied in twenty-five critically ill patients with catecholamine-dependent heart failure. Following sedation with midazolam (0.15 +/- 0.07, mg.kg-1.h-1) and sufentanil (0.88 +/- 0.33 microgram.kg-1.h-1), patients with impaired left ventricular function (left ventricular ejection fraction area 30 +/- 7%) were randomly assigned to receive ketamine (2.5 +/- 0.9 mg.kg-1.h-1) and midazolam (Group A) or remained on sufentanil/midazolam (Group B). Haemodynamic measurements were performed throughout the first 24 hours after randomization. In group A cardiac index decreased by 21% (P = 0.01), mean arterial pressure increased by 13% (P = 0.01), mean pulmonary artery pressure by 14% (P = 0.04), pulmonary capillary wedge pressure by 20% (P = 0.03), and systemic vascular resistance index by 38% (P < 0.001). No significant cardiovascular effects were observed in Group B. Neither group had significant changes of exogenous catecholamine requirement. In conclusion, ketamine exhibits potential negative cardiovascular effects in patients with catecholamine-dependent heart failure. Therefore, ketamine should not be considered a first line drug for longterm sedation of patients with impaired left ventricular function.
Anaesthesia and intensive care 07/1997; 25(3):255-9. · 1.28 Impact Factor
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ABSTRACT: Increased expression of plasminogen activator inhibitor-1 (PAI-1) mRNA in atherosclerotic human arteries suggests a linkage between PAI-1 gene expression and cellular proliferation, the fundamental feature of atherosclerosis. To investigate whether smooth muscle cell (SMC) proliferation influences overall fibrinolytic properties of the vascular wall, we examined the effect of serial in vitro passaging of human SMCs on tissue plasminogen activator (TPA) and PAI-1 synthesis levels as well as the ability to modulate TPA and PAI-1 synthesis of human umbilical vein endothelial cells (HUVECs). As in vivo correlates for such late-passage cells in culture, SMCs derived from human atherosclerotic plaques were used, because they are thought to have already undergone numerous cell doublings. We observed an increase of PAI-1 secretion (from 591 +/- 106 to 2952 +/- 290 ng PAI-1.10(5) cells-1.24 h-1) with a concomitant fourfold to fivefold increase of PAI-1 mRNA levels, as well as a decrease of TPA secretion (from 118 +/- 34 to 8 +/- 1.3 ng TPA.10(5) cells-1.24 h-1) and a twofold to threefold decrease of TPA mRNA levels with increasing in vitro passage number (from passage 3 to 11) of normal pulmonary artery smooth muscle cells (PASMCs) (P < .05). SMCs derived from atherosclerotic plaques of coronary arteries (CASMCs) displayed higher levels of PAI-1 antigen synthesis (3093 +/- 507 ng PAI-1.10(5) cells-1.24 h-1) with an approximately twofold increase of PAI-1 mRNA levels, as well as decreased levels of TPA antigen synthesis (10 +/- 1.6 ng TPA.10(5) cells-1.24 h-1) with an approximately 1.5- to 2-fold decrease of TPA mRNA levels in passage 1, compared with their counterparts derived from normal-appearing arterial tissue of the same vessel (1794 +/- 525 ng PAI-1.10(5) cells-1.24 h-1; 17 +/- 5 ng TPA.10(5) cells-1.24 h-1) (P < .001; P < .01). Incubation of HUVEC cultures with the 24-hour conditioned media (CM) of early-passage PASMCs decreased endothelial PAI-1 antigen synthesis by approximately 42% (P < .001) and endothelial PAI-1 mRNA levels about twofold to threefold (P < .001), whereas by incubation with the 24-hour CM of late-passage PASMCs, endothelial PAI-1 antigen synthesis was upregulated by 68% (P = .001), with a concomitant twofold increase of endothelial PAI-1 mRNA levels (P < .001). The apparent MW of this heat- and acid-stable PAI-1 upregulating factor appears to be between 50 and 100 kD, as judged by ultrafiltration. Incubation of HUVEC cultures with the 24-hour CM of early-passage CASMCs derived from normal-appearing arterial tissue showed no significant influence on endothelial PAI-1 synthesis, whereas incubation with late-passage normal CASMCs, as well as early-passage atherosclerotic CASMCs from the same vessel, increased endothelial PAI-1 antigen secretion by 45% and 48% (P < .001), with a concomitant 1.5 fold to 2-fold increase of endothelial PAI-1 mRNA levels (P < .05). No significant change in endothelial TPA synthesis was observed by incubation with CM of either PASMCs (early or late passage) or CASMCs (atherosclerotic or normal). These data suggest that SMC proliferation is associated with (1) increased SMC PAI-1 synthesis as well as decreased TPA synthesis and (2) upregulation of endothelial PAI-1 synthesis by SMC CM. This phenomenon is observed with either late passages of normal PASMCs and CASMCs or early passages of atherosclerotic plaque CASMCs. This suggests that proliferating SMCs are a major regulator of the fibrinolytic potential within the vessel wall, thereby contributing to the thrombotic risk associated with the development of atherosclerosis.
Arteriosclerosis Thrombosis and Vascular Biology 05/1997; 17(4):723-30. · 6.37 Impact Factor
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ABSTRACT: Currently used methods for assessment of coronary flow reserve are invasive and require extensive laboratory equipment. Recently, noninvasive assessment of coronary flow reserve by transesophageal Doppler evaluation of coronary sinus (CS) or left anterior descending coronary artery (LAD) flow has been proposed. Direct comparison between these two techniques is lacking.
Doppler recordings of CS and LAD flow velocity were obtained before and after 0.6 mg/kg/5 min dipyridamole in 16 patients with significant stenosis of the LAD (Group A) and in 14 control patients (Group B). Flow recordings and all measurements were performed in a blinded manner. For assessment of coronary flow reserve, Doppler measurements after dipyridamole were divided by the respective baseline values.
Doppler studies of the CS and LAD were feasible in 30 of 30 (100%) and 23 of 30 (71%) patients, respectively. Analyzing the maximum flow velocities, coronary flow reserve in Groups A and B was 1.18 +/- 0.28 and 1.68 +/- 0.53 with CS recordings and 1.78 +/- 0.83 and 2.51 +/- 0.76 with LAD recordings, respectively. Analyzing the velocity time integrals, coronary flow reserve in Groups A and B was 1.53 +/- 0.68 and 2.59 +/- 0.74 with CS recordings and 1.77 +/- 0.38 and 2.68 +/- 0.93 with LAD recordings, respectively. Correlation between LAD and CS recordings was 0.69 (p < 0.001), when coronary flow reserve was calculated from the velocity time integral and 0.68 (p < 0.001) when the maximum flow velocities were used.
Both transesophageal Doppler techniques might be useful for noninvasive assessment of coronary flow reserve.
Clinical Cardiology 04/1997; 20(3):225-31. · 2.15 Impact Factor
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ABSTRACT: To demonstrate that emergency aortic valve replacement can be successfully performed in patients with critical aortic stenosis and reduced left ventricular function even in cardiogenic shock with associated severe multiple organ failure.
Retrospective, consecutive case series.
Multidisciplinary intensive care unit of a tertiary care university hospital.
Five patients admitted to the intensive care unit with critical aortic stenosis (aortic valve area 0.56 +/- 0.13 cm2) and greatly reduced left ventricular ejection fraction (20 +/- 3%) in prolonged cardiogenic shock and associated multiple organ failure (Multiple organ failure score 6.8 +/- 0.5; Acute Physiology, Age, and Chronic Health Evaluation III score 91 +/- 27).
Emergency aortic valve replacement.
All patients survived with full recovery of organ function. At follow-up (18 +/- 10 months) all patients were in New York Heart Association functional class I or II with improvement of left ventricular ejection fraction to 48 +/- 25%.
This excellent outcome suggests that emergency aortic valve replacement should be strongly considered in patients with critical aortic stenosis even in cardiogenic shock and multiple organ failure.
Intensive Care Medicine 04/1997; 23(3):297-300. · 5.40 Impact Factor
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ABSTRACT: Objective: To demonstrate that emergency aortic valve replacement can be successfully performed in patients with critical aortic stenosis
and reduced left ventricular function even in cardiogenic shock with associated severe multiple organ failure. Design: Retrospective, consecutive case series. Setting: Multidisciplinary intensive care unit of a tertiary care university hospital. Patients: Five patients admitted to the intensive care unit with critical aortic stenosis (aortic valve area 0.56 ± 0.13 cm2) and greatly reduced left ventricular ejection fraction (20 ± 3 %) in prolonged cardiogenic shock and associated multiple
organ failure (Multiple organ failure score 6.8 ± 0.5; Acute Physiology, Age, and Chronic Health Evaluation III score 91 ±
27). Intervention: Emergency aortic valve replacement. Results: All patients survived with full recovery of organ function. At follow-up (18 ± 10 months) all patients were in New York
Heart Association functional class I or II with improvement of left ventricular ejection fraction to 48 ± 25 %. Conclusions: This excellent outcome suggests that emergency aortic valve replacement should be strongly considered in patients with critical
aortic stenosis even in cardiogenic shock and multiple organ failure.
Intensive Care Medicine 02/1997; 23(3):297-300. · 5.40 Impact Factor
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ABSTRACT: Large epidemiological studies demonstrate only moderate reduction in the incidence of coronary artery disease by antihypertensive drug treatment. This is attributed to the prevalence of multiple risk factors in hypertensive patients and to possible adverse metabolic effects of antihypertensive drugs which may counteract their ability to reduce the risk of cardiovascular disease. The choices for pharmacological blood pressure reduction are divided between five classes with similar antihypertensive efficacy but markedly different influence on coronary risk factors. Hence, the clinician has to consider the prevalence of coexisting coronary risk factors, comorbidity as well as the efficacy, side effects, and mechanisms of drug action.
Wiener klinische Wochenschrift 01/1997; 108(24):775-80. · 0.81 Impact Factor
