63 results on '"Bronzwaer JG"'
Search Results
2. Letter by Knaapen et al regarding article, 'hemodynamic effects of long-term cardiac resynchronization therapy: analysis by pressure-volume loops'.
- Author
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Knaapen P, Allaart CP, de Cock CC, and Bronzwaer JG
- Published
- 2006
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3. Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention.
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Teunissen PF, de Waard GA, Hollander MR, Robbers LF, Danad I, Biesbroek PS, Amier RP, Echavarría-Pinto M, Quirós A, Broyd C, Heymans MW, Nijveldt R, Lammertsma AA, Raijmakers PG, Allaart CP, Lemkes JS, Appelman YE, Marques KM, Bronzwaer JG, Horrevoets AJ, van Rossum AC, Escaned J, Beek AM, Knaapen P, and van Royen N more...
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- Aged, Blood Flow Velocity, Coronary Vessels diagnostic imaging, Echocardiography, Doppler, Female, Humans, Magnetic Resonance Angiography, Male, Middle Aged, Positron-Emission Tomography, Prospective Studies, Vascular Resistance physiology, Coronary Circulation physiology, Coronary Vessels physiopathology, Myocardial Infarction physiopathology, Myocardial Infarction surgery, Percutaneous Coronary Intervention adverse effects
- Abstract
Background: A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET)., Methods and Results: Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04)., Conclusions: Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow., Clinical Trial Registration Url: http://www.trialregister.nl. Unique identifier: NTR3164., (© 2015 American Heart Association, Inc.) more...
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- 2015
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4. Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements.
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de Roest GJ, Allaart CP, Kleijn SA, Delnoy PP, Wu L, Hendriks ML, Bronzwaer JG, van Rossum AC, and de Cock CC
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- Aged, Female, Humans, Longitudinal Studies, Male, Middle Aged, Patient Selection, Prognosis, Prospective Studies, ROC Curve, Treatment Outcome, Cardiac Resynchronization Therapy methods, Heart Failure therapy, Hemodynamics, Ventricular Dysfunction, Left therapy
- Abstract
Aims: Invasive assessment of acute haemodynamic response to biventricular pacing has been proposed as a tool to determine individual response and to optimize the effects of CRT. However, the long-term results of this approach have been poorly studied. The present study relates acute haemodynamic effects of CRT to long-term outcome., Methods and Results: Forty-one patients were analysed in the present study. During temporary biventricular pacing before implantation, acute changes in LV pump function were assessed by pressure-volume loop measurements and related to long-term response after CRT. In the study population [30 (71%) men, NYHA class 2.9 ± 0.4, EF 28 ± 7%, QRS 150 ± 25 ms], baseline mean stroke work (SW) and dP/dt(max) were 4.6 ± 2.6 L × mmHg and 874 ± 259 mmHg/s, respectively. During biventricular pacing, mean SW and dP/dt(max) increased significantly by 43 ± 39% (+ 2.2 ± 2.4 L × mmHg, P < 0.001) and 13 ± 18% (+ 96 ± 136 mmHg/s, P < 0.001), respectively. In long-term responders (n = 29, 71%) compared with non-responders (n = 12, 29%), the acute increase in SW was significantly higher (+57 ± 33% vs. + 10 ± 30%, P < 0.001), whereas the acute increase in dP/dt(max) was not significantly different between responders and non-responders (+ 15 ± 18% vs. 6 ± 15%, P = 0.139). Receiver operating characteristic (ROC) curve analysis indicated that SW was superior to dP/dt(max), QRS duration and LV dyssynchrony in prediction of response to CRT. A cut-off value for SW of 20% yielded a sensitivity of 90% and specificity of 75% to predict reverse remodelling at 6 months., Conclusion: Invasive assessment of acute haemodynamics is a reliable tool to determine individual response to CRT. An acute increase in SW predicts long-term response to CRT with a higher accuracy than an acute increase in dP/dt(max), baseline QRS duration, and degree of LV mechanical dyssynchrony. more...
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- 2013
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5. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction.
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van Heerebeek L, Hamdani N, Falcão-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW, Niessen HW, and Paulus WJ
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- Aortic Valve Stenosis enzymology, Aortic Valve Stenosis epidemiology, Aortic Valve Stenosis pathology, Biopsy, Cohort Studies, Comorbidity, Cyclic GMP analysis, Diabetes Mellitus enzymology, Diabetes Mellitus epidemiology, Diabetes Mellitus pathology, Female, Heart Failure epidemiology, Heart Failure pathology, Heart Failure physiopathology, Humans, Male, Middle Aged, Myocardium pathology, Natriuretic Peptide, Brain biosynthesis, Obesity enzymology, Obesity epidemiology, Obesity pathology, Oxidative Stress physiology, Tyrosine analogs & derivatives, Tyrosine biosynthesis, Cyclic GMP-Dependent Protein Kinases metabolism, Heart physiopathology, Heart Failure enzymology, Myocardium enzymology, Stroke Volume physiology
- Abstract
Background: Prominent features of myocardial remodeling in heart failure with preserved ejection fraction (HFPEF) are high cardiomyocyte resting tension (F(passive)) and cardiomyocyte hypertrophy. In experimental models, both reacted favorably to raised protein kinase G (PKG) activity. The present study assessed myocardial PKG activity, its downstream effects on cardiomyocyte F(passive) and cardiomyocyte diameter, and its upstream control by cyclic guanosine monophosphate (cGMP), nitrosative/oxidative stress, and brain natriuretic peptide (BNP). To discern altered control of myocardial remodeling by PKG, HFPEF was compared with aortic stenosis and HF with reduced EF (HFREF)., Methods and Results: Patients with HFPEF (n=36), AS (n=67), and HFREF (n=43) were free of coronary artery disease. More HFPEF patients were obese (P<0.05) or had diabetes mellitus (P<0.05). Left ventricular myocardial biopsies were procured transvascularly in HFPEF and HFREF and perioperatively in aortic stenosis. F(passive) was measured in cardiomyocytes before and after PKG administration. Myocardial homogenates were used for assessment of PKG activity, cGMP concentration, proBNP-108 expression, and nitrotyrosine expression, a measure of nitrosative/oxidative stress. Additional quantitative immunohistochemical analysis was performed for PKG activity and nitrotyrosine expression. Lower PKG activity in HFPEF than in aortic stenosis (P<0.01) or HFREF (P<0.001) was associated with higher cardiomyocyte F(passive) (P<0.001) and related to lower cGMP concentration (P<0.001) and higher nitrosative/oxidative stress (P<0.05). Higher F(passive) in HFPEF was corrected by in vitro PKG administration., Conclusions: Low myocardial PKG activity in HFPEF was associated with raised cardiomyocyte F(passive) and was related to increased myocardial nitrosative/oxidative stress. The latter was probably induced by the high prevalence in HFPEF of metabolic comorbidities. Correction of myocardial PKG activity could be a target for specific HFPEF treatment. more...
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- 2012
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6. Improved clinical outcome after invasive management of patients with recent myocardial infarction and proven myocardial viability: primary results of a randomized controlled trial (VIAMI-trial).
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van Loon RB, Veen G, Baur LH, Kamp O, Bronzwaer JG, Twisk JW, Verheugt FW, and van Rossum AC
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- Angina, Unstable etiology, Angina, Unstable prevention & control, Anticoagulants therapeutic use, Chi-Square Distribution, Disease-Free Survival, Echocardiography, Stress, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction diagnostic imaging, Myocardial Infarction mortality, Myocardial Infarction pathology, Netherlands, Platelet Aggregation Inhibitors therapeutic use, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Secondary Prevention, Stents, Thrombolytic Therapy, Time Factors, Tissue Survival, Treatment Outcome, Angioplasty, Balloon, Coronary adverse effects, Angioplasty, Balloon, Coronary instrumentation, Angioplasty, Balloon, Coronary mortality, Myocardial Infarction therapy, Myocardium pathology
- Abstract
Background: Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA)., Methods: Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded., Results: The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051)., Conclusion: We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability., Trial Registration: ClinicalTrials.gov: NCT00149591. more...
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- 2012
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7. Effects of QRS duration and pacing location on pressure-volume loop evaluation of cardiac resynchronization therapy in end-stage heart failure.
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de Roest GJ, Allaart CP, de Haan S, Hendriks ML, Bronzwaer JG, van Rossum AC, and de Cock CC
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- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Heart Failure diagnosis, Heart Failure therapy, Heart Ventricles diagnostic imaging, Heart Ventricles pathology, Humans, Male, Middle Aged, Treatment Outcome, Ultrasonography, Cardiac Pacing, Artificial methods, Electrocardiography, Heart Failure physiopathology, Heart Ventricles physiopathology, Magnetic Resonance Imaging, Cine methods, Ventricular Pressure physiology
- Abstract
Cardiac resynchronization therapy (CRT) decreases the morbidity and mortality in patients with end-stage heart failure. However, patient selection remains challenging, because a considerable 30% to 50% do not respond. Controversy exists on the cutoff values for the QRS duration and the optimal lead location. The present study relates these parameters on an individual basis to acute pump function improvement using invasively obtained pressure-volume loops. Fifty-seven patients with symptomatic end-stage heart failure were included in our temporary biventricular stimulation study and were grouped according to the QRS duration (QRS <20 ms, QRS ≥120 ms but <150 ms, and QRS ≥150 ms). All patients underwent pressure-volume loop assessment of the response to biventricular pacing, comparing the baseline measurements to both right ventricular apex pacing combined with a left ventricular lead in the posterolateral and anterolateral region of the LV. Group analysis during conventional (posterolateral and right ventricular apex) CRT did not show improvement in stroke work and dP/dt(max) (-2%, p = NS; and -7%; p <0.001) in the narrow QRS group but a significant increase in the intermediate (+27%, p = 0.020, and +5%, p = 0.044) and wide (+48%, p = 0.002, and +18%, p <0.001) QRS groups. CRT using the anterolateral and right ventricular apex configuration evoked a consistently lower response compared to posterolateral and right ventricular apex, resulting in a significant hemodynamic deterioration in the narrow QRS group. However, analysis on an individual basis identified 25% of patients with narrow QRS duration showing possible hemodynamic benefit from CRT compared to 83% of patients with intermediate and wide QRS combined. In contrast, 15% of patients had deterioration by conventional (posterolateral right ventricular apex) CRT in the intermediate and wide QRS groups compared to 31% in the narrow QRS group; 19% of patients could be improved by lead placement in the anterolateral rather than the posterolateral region. In conclusion, the acute hemodynamic response to CRT is generally in line with the long-term results from large randomized trials; however, the individual variation is large. The temporary biventricular stimulation protocol might aid in individual patient selection and in research aiming at a reduction of nonresponders and improvement in lead positioning., (Copyright © 2011 Elsevier Inc. All rights reserved.) more...
- Published
- 2011
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8. Implementation of a prehospital triage system for patients with chest pain and logistics for primary percutaneous coronary intervention in the region of Amsterdam, the Netherlands.
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Adams R, Appelman Y, Bronzwaer JG, Slagboom T, Amoroso G, van Exter P, Tijssen GP, and de Winter RJ
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- Diagnosis, Differential, Electrocardiography, Female, Humans, Male, Middle Aged, Netherlands, Time Factors, Angioplasty, Balloon, Coronary, Chest Pain diagnosis, Myocardial Infarction diagnosis, Myocardial Infarction therapy, Triage
- Abstract
We aimed to describe the logistics of a prehospital triage system for patients with acute chest pain in the region of Amsterdam, The Netherlands. Ambulance electrocardiograms (ECGs) were evaluated immediately in 1 of the percutaneous coronary intervention (PCI)-capable centers. Patients accepted for primary PCI (PPCI) were directly transferred to the catheterization laboratory. Two thousand three hundred fifty ECGs of 2,192 patients were transmitted to the region's intervention centers. Median duration of chest complaints before ambulance dispatch was 67 minutes; ambulance crews recorded the first ECG within 7 minutes after arrival. Actual transmission of the ECG took an additional (median) 10 minutes. Seven hundred eleven patients (32.4%) were transported to the catheter laboratory and were treated with PPCI. Time between first prehospital ECG and start of PPCI procedure was 66 minutes. The PPCI procedure started 36 minutes after ambulance arrival at the hospital. In conclusion, the results of this study compare favorably to other reported performances of prehospital triage systems of PPCI for ST-segment elevated myocardial infarction and demonstrate that the European Society of Cardiology and American Heart Association guidelines for treatment of patients with ST-segment elevated myocardial infarction can be met., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...
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- 2010
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9. Patients with coronary stenosis and a fractional flow reserve of ≥0.75 measured in daily practice at the VU University Medical Center.
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Oud N, Marques KM, Bronzwaer JG, Brinckman S, Allaart CP, de Cock CC, and Appelman Y
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Objectives. The aim of this study was to analyse the rate of major adverse clinical events in patients with coronary artery disease and a fractional flow reserve (FFR) of ≥0.75 and deferred for coronary intervention in daily practice. Methods. From 1 January to 31 December 2006, FFR measurement was initiated in 122 patients (5%) out of 2444 patients referred for coronary angiography. In two patients FFR measurement failed and in one patient the FFR value could no longer be traced in the documents. Thus, 119 patients (84 men, 64 years, range 41-85) were included in the evaluation (145 lesions). Major adverse clinical events (death, myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)) and the presence of angina were evaluated at follow-up. Furthermore a cost-effectiveness analysis was performed.Results. In 93 patients (76%) the FFR value was ≥0.75. Seventy of these 93 patients (76%) were treated with medication alone or underwent PCI for a different lesion (medical treatment group). Average duration of follow-up of all 119 patients was 22 months (range 4 days to 30 months). In the medical treatment group seven patients (10%) experienced a major adverse clinical event related to the FFR-evaluated lesion during follow-up. In this study population, the use of FFR measurement is cost-reducing provided that at least 65% of the patients in the medical treatment group has had a PCI with stent implantation when the use of FFR measurement is impossible. In this case, the decision to use PCI with stent implantation is purely based on the angiogram. Conclusions. In patients with a coronary stenosis based on visual assessment and an FFR of ≥0.75 deferral of PCI or CABG is safe in daily clinical practice and saves money. (Neth Heart J 2010;18:402-7.). more...
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- 2010
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10. Diastolic and systolic heart failure: different stages or distinct phenotypes of the heart failure syndrome?
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Bronzwaer JG and Paulus WJ
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- Global Health, Humans, Morbidity, Phenotype, Survival Rate, Heart Failure, Diastolic epidemiology, Heart Failure, Diastolic genetics, Heart Failure, Diastolic physiopathology, Heart Failure, Systolic epidemiology, Heart Failure, Systolic genetics, Heart Failure, Systolic physiopathology, Stroke Volume physiology, Ventricular Function, Left physiology
- Abstract
It remains uncertain if diastolic heart failure (DHF) is a distinct HF phenotype or a precursor stage of systolic HF (SHF). The unimodal distribution of left ventricular ejection fraction (LVEF) in HF, depressed LV long-axis shortening in DHF, and progression to eccentric LV remodeling in hypertension favor DHF and SHF as successive stages. These arguments are countered by the bimodal distribution of LVEF after correction for gender, by the preserved LV twist in DHF and by the low incidence of eccentric LV remodeling in hypertension. Clinical features, LV anatomy and histology, cardiomyocyte stiffness, myocardial effects of diabetes, and the response to HF therapy support DHF and SHF as distinct phenotypes. Comparison of the myocardial signal transduction cascades that drive LV remodeling in DHF and SHF may solve the controversy. This review analyzes arguments supporting DHF and SHF as successive stages or distinct phenotypes of the HF syndrome. more...
- Published
- 2009
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11. Distinct myocardial effects of beta-blocker therapy in heart failure with normal and reduced left ventricular ejection fraction.
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Hamdani N, Paulus WJ, van Heerebeek L, Borbély A, Boontje NM, Zuidwijk MJ, Bronzwaer JG, Simonides WS, Niessen HW, Stienen GJ, and van der Velden J
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- Aged, Cross-Sectional Studies, Female, Heart Failure pathology, Heart Failure physiopathology, Humans, Male, Microfilament Proteins metabolism, Middle Aged, Myocytes, Cardiac pathology, Phosphorylation, Stroke Volume drug effects, Adrenergic beta-Antagonists therapeutic use, Heart Failure drug therapy, Myocardium pathology, Myocardium ultrastructure, Stroke Volume physiology, Ventricular Dysfunction, Left drug therapy, Ventricular Dysfunction, Left pathology, Ventricular Dysfunction, Left physiopathology
- Abstract
Aims: Left ventricular (LV) myocardial structure and function differ in heart failure (HF) with normal (N) and reduced (R) LV ejection fraction (EF). This difference could underlie an unequal outcome of trials with beta-blockers in heart failure with normal LVEF (HFNEF) and heart failure with reduced LVEF (HFREF) with mixed results observed in HFNEF and positive results in HFREF. To investigate whether beta-blockers have distinct myocardial effects in HFNEF and HFREF, myocardial structure, cardiomyocyte function, and myocardial protein composition were compared in HFNEF and HFREF patients without or with beta-blockers., Methods and Results: Patients, free of coronary artery disease, were divided into beta-(HFNEF) (n = 16), beta+(HFNEF) (n = 16), beta-(HFREF) (n = 17), and beta+(HFREF) (n = 22) groups. Using LV endomyocardial biopsies, we assessed collagen volume fraction (CVF) and cardiomyocyte diameter (MyD) by histomorphometry, phosphorylation of myofilamentary proteins by ProQ-Diamond phosphostained 1D-gels, and expression of beta-adrenergic signalling and calcium handling proteins by western immunoblotting. Cardiomyocytes were also isolated from the biopsies to measure active force (F(active)), resting force (F(passive)), and calcium sensitivity (pCa(50)). Myocardial effects of beta-blocker therapy were either shared by HFNEF and HFREF, unique to HFNEF or unique to HFREF. Higher F(active), higher pCa(50), lower phosphorylation of troponin I and myosin-binding protein C, and lower beta(2) adrenergic receptor expression were shared. Higher F(passive), lower CVF, lower MyD, and lower expression of stimulatory G protein were unique to HFNEF and lower expression of inhibitory G protein was unique to HFREF., Conclusion: Myocardial effects unique to either HFNEF or HFREF could contribute to the dissimilar outcome of beta-blocker therapy in both HF phenotypes. more...
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- 2009
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12. Left ventricular torsion: an expanding role in the analysis of myocardial dysfunction.
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Rüssel IK, Götte MJ, Bronzwaer JG, Knaapen P, Paulus WJ, and van Rossum AC
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- Animals, Echocardiography, Heart Diseases pathology, Heart Ventricles pathology, Heart Ventricles physiopathology, Humans, Magnetic Resonance Imaging, Models, Cardiovascular, Heart Diseases physiopathology, Myocardial Contraction, Myocardium pathology, Torsion, Mechanical, Ventricular Function, Left
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During left ventricular (LV) torsion, the base rotates in an overall clockwise direction and the apex rotates in a counterclockwise direction when viewed from apex to base. LV torsion is followed by rapid untwisting, which contributes to ventricular filling. Because LV torsion is directly related to fiber orientation, it might depict subclinical abnormalities in heart function. Recently, ultrasound speckle tracking was introduced for quantification of LV torsion. This fast, widely available technique may contribute to a more rapid introduction of LV torsion as a clinical tool for detection of myocardial dysfunction. However, knowledge of the exact function and structure of the heart is fundamental for understanding the value of LV torsion. LV torsion has been investigated with different measurement methods during the past 2 decades, using cardiac magnetic resonance as the gold standard. The results obtained over the years are helpful for developing a standardized method to quantify LV torsion and have facilitated the interpretation and value of LV torsion before it can be used as a clinical tool. more...
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- 2009
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13. Hypophosphorylation of the Stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium.
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Borbély A, Falcao-Pires I, van Heerebeek L, Hamdani N, Edes I, Gavina C, Leite-Moreira AF, Bronzwaer JG, Papp Z, van der Velden J, Stienen GJ, and Paulus WJ
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- Aged, Biopsy, Connectin, Elasticity, Female, Heart Failure pathology, Humans, Male, Middle Aged, Myocardium pathology, Myocytes, Cardiac pathology, Phosphorylation, Protein Isoforms metabolism, Sarcomeres pathology, Heart Failure metabolism, Muscle Proteins metabolism, Myocardium metabolism, Myocytes, Cardiac metabolism, Protein Kinases metabolism, Sarcomeres metabolism
- Abstract
High diastolic stiffness of failing myocardium results from interstitial fibrosis and elevated resting tension (F(passive)) of cardiomyocytes. A shift in titin isoform expression from N2BA to N2B isoform, lower overall phosphorylation of titin, and a shift in titin phosphorylation from N2B to N2BA isoform can raise F(passive) of cardiomyocytes. In left ventricular biopsies of heart failure (HF) patients, aortic stenosis (AS) patients, and controls (CON), we therefore related F(passive) of isolated cardiomyocytes to expression of titin isoforms and to phosphorylation of titin and titin isoforms. Biopsies were procured by transvascular technique (44 HF, 3 CON), perioperatively (25 AS, 4 CON), or from explanted hearts (4 HF, 8 CON). None had coronary artery disease. Isolated, permeabilized cardiomyocytes were stretched to 2.2-microm sarcomere length to measure F(passive). Expression and phosphorylation of titin isoforms were analyzed using gel electrophoresis with ProQ Diamond and SYPRO Ruby stains and reported as ratio of titin (N2BA/N2B) or of phosphorylated titin (P-N2BA/P-N2B) isoforms. F(passive) was higher in HF (6.1+/-0.4 kN/m(2)) than in CON (2.3+/-0.3 kN/m(2); P<0.01) or in AS (2.2+/-0.2 kN/m(2); P<0.001). Titin isoform expression differed between HF (N2BA/N2B=0.73+/-0.06) and CON (N2BA/N2B=0.39+/-0.05; P<0.001) and was comparable in HF and AS (N2BA/N2B=0.59+/-0.06). Overall titin phosphorylation was also comparable in HF and AS, but relative phosphorylation of the stiff N2B titin isoform was significantly lower in HF (P-N2BA/P-N2B=0.77+/-0.05) than in AS (P-N2BA/P-N2B=0.54+/-0.05; P<0.01). Relative hypophosphorylation of the stiff N2B titin isoform is a novel mechanism responsible for raised F(passive) of human HF cardiomyocytes. more...
- Published
- 2009
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14. Recurrent ventricular fibrillation caused by coronary artery spasm leading to implantable cardioverter defibrillator implantation.
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Hendriks ML, Allaart CP, Bronzwaer JG, Res JJ, and de Cock CC
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- Humans, Middle Aged, Coronary Vasospasm complications, Coronary Vasospasm prevention & control, Defibrillators, Implantable, Ventricular Dysfunction, Right etiology, Ventricular Dysfunction, Right prevention & control, Ventricular Fibrillation etiology, Ventricular Fibrillation prevention & control
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Coronary artery spasm has been known to induce ischaemia and ventricular arrhythmias. We present a case of recurrent ventricular fibrillation caused by spasm-associated transmural myocardial ischaemia. During an intra-coronary acetylcholine provocation test, severe coronary spasm could be induced. The patient was treated with a hybrid approach of medication and an implantable defibrillator. more...
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- 2008
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15. Nitric oxide: the missing lusitrope in failing myocardium.
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Bronzwaer JG and Paulus WJ
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- Animals, Dogs, Humans, Myocardial Contraction physiology, Nitric Oxide pharmacology, Nitric Oxide Synthase physiology, Heart Failure, Systolic blood, Heart Failure, Systolic physiopathology, Myocardium metabolism, Nitric Oxide physiology, Nitric Oxide Synthase metabolism, Ventricular Dysfunction, Left metabolism
- Published
- 2008
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16. Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension.
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Overbeek MJ, Lankhaar JW, Westerhof N, Voskuyl AE, Boonstra A, Bronzwaer JG, Marques KM, Smit EF, Dijkmans BA, and Vonk-Noordegraaf A
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- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Hemodynamics, Humans, Hypertension, Pulmonary etiology, Male, Middle Aged, Scleroderma, Systemic complications, Stroke Volume, Ventricular Dysfunction, Right diagnosis, Hypertension, Pulmonary physiopathology, Myocardial Contraction, Scleroderma, Systemic physiopathology, Ventricular Dysfunction, Right physiopathology
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Since systemic sclerosis (SSc) also involves the heart, the aim of the present study was to evaluate possible differences in right ventricular (RV) pump function between SSc-associated pulmonary arterial hypertension (PAH; SScPAH) and idiopathic PAH (IPAH). In 13 limited cutaneous SScPAH and 17 IPAH patients, RV pump function was described using the pump function graph, which relates mean RV pressure ((RV)) and stroke volume index (SVI). Differences in pump function result in shift or rotation of the pump function graph. (RV) and SVI were measured using standard catheterisation. The hypothetical isovolumic (RV) ((RV,iso)) was estimated using a single-beat method. The pump function graph was approximated by a parabola: (RV) = (RV,iso)[1-(SVI/SVI(max))(2)], where SVI(max )is the hypothetical maximal SVI at zero (RV), enabling calculation of SVI(max). There were no differences in SVI and SVI(max). Both (RV) and (RV,iso) were significantly lower in SScPAH than in IPAH ((RV) 30.7+/-8.5 versus 41.2+/-9.4 mmHg; (RV,iso) 43.1+/-12.4 versus 53.5+/-10.0 mmHg). Since higher pressures were found at similar SVI, the difference in the pump function graph results from lower contractility in SScPAH than in IPAH. Right ventricular contractility is lower in systemic sclerosis-associated pulmonary arterial hypertension than in idiopathic pulmonary arterial hypertension. more...
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- 2008
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17. Myofilament degradation and dysfunction of human cardiomyocytes in Fabry disease.
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Chimenti C, Hamdani N, Boontje NM, DeCobelli F, Esposito A, Bronzwaer JG, Stienen GJ, Russo MA, Paulus WJ, Frustaci A, and van der Velden J
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- Actin Cytoskeleton physiology, Adult, Biomechanical Phenomena, Collagen metabolism, Cyclic AMP-Dependent Protein Kinases pharmacology, Desmin metabolism, Fabry Disease physiopathology, Glycosphingolipids metabolism, Humans, In Vitro Techniques, Male, Middle Aged, Mutation, Myocardial Contraction, Myocardium metabolism, Myocardium pathology, Myocytes, Cardiac drug effects, Myocytes, Cardiac physiology, Troponin I metabolism, alpha-Galactosidase genetics, alpha-Galactosidase metabolism, Actin Cytoskeleton pathology, Fabry Disease pathology, Myocytes, Cardiac pathology
- Abstract
Early detection of myocardial dysfunction in Fabry disease (FD) cardiomyopathy suggests the contribution of myofilament structural alterations. Six males with untreated FD cardiomyopathy submitted to cardiac studies, including tissue Doppler imaging and left ventricular endomyocardial biopsy. Active and resting tensions before and after treatment with protein kinase A (PKA) were determined in isolated Triton-permeabilized cardiomyocytes. Cardiomyocyte cross-sectional area, glycosphingolipid vacuole area, myofibrillolysis, and extent of fibrosis were also determined. Biopsies of mitral stenosis in patients with normal left ventricles served as controls. Active tension was four times lower in FD cardiomyocytes and correlated with extent of myofibrillolysis. Resting tension was six times higher in FD cardiomyocytes than in controls. PKA treatment decreased resting tension but did not affect active force. Protein analysis revealed troponin I and desmin degradation products. FD cardiomyocytes were significantly larger and filled with glycosphingolipids. Fibrosis was mildly increased compared with controls. Tissue Doppler imaging lengthening and shortening velocities were reduced in FD cardiomyocytes compared with controls, correlating with resting and active tensions, respectively, but not with cardiomyocyte area, percentage of glycosphingolipids, or extent of fibrosis. In conclusion, myofilament degradation and dysfunction contribute to FD cardiomyopathy. Partial reversal of high resting tension after pharmacological PKA treatment of cardiomyocytes suggests potential benefits from enzyme replacement therapy and/or energy-releasing agents. more...
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- 2008
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18. Percutaneous coronary intervention with off-site cardiac surgical backup.
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de Boer MJ, Bronzwaer JG, and Boers M
- Subjects
- Health Services Accessibility, Humans, Patient Transfer, Time Factors, Treatment Outcome, Triage, Angioplasty, Balloon, Coronary statistics & numerical data, Myocardial Infarction therapy
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- 2008
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19. High dose adenosine for suboptimal myocardial reperfusion after primary PCI: A randomized placebo-controlled pilot study.
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Stoel MG, Marques KM, de Cock CC, Bronzwaer JG, von Birgelen C, and Zijlstra F
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- Aged, Aged, 80 and over, Combined Modality Therapy, Coronary Angiography, Coronary Vessels drug effects, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Infusions, Intralesional, Male, Middle Aged, Myocardial Infarction mortality, Myocardial Reperfusion methods, Probability, Reference Values, Risk Assessment, Severity of Illness Index, Survival Rate, Treatment Outcome, Adenosine administration & dosage, Angioplasty, Balloon, Coronary methods, Electrocardiography, Myocardial Infarction diagnosis, Myocardial Infarction therapy
- Abstract
Objectives: This study was designed to investigate the influence of high dose intracoronary adenosine on persistent ST-segment elevation after primary percutaneous coronary intervention (PCI)., Background: After successful PCI for acute myocardial infarction 40-50% of patients show persistent ST-segment elevation indicating suboptimal myocardial reperfusion. Adenosine has been studied to ameliorate reperfusion and is frequently used in a variety of doses, but there are no prospective studies to support its use for treatment of suboptimal reperfusion., Methods: We conducted a blinded, randomized, and placebo-controlled study with high dose intracoronary adenosine in 51 patients with <70% ST-segment resolution (STRes) after successful primary PCI. All patients were treated with stents and abciximab., Results: Immediately after adenosine, significantly more patients showed optimal (>70%) STRes compared with placebo (33% versus 9%, P < 0.05). Mean STRes was higher after adenosine (35.4% versus 23.0%, P < 0.05). In addition, TIMI frame count was significant lower (15.7 versus 30.2, P < 0.005), Myocardial Blush Grade was higher (2.7 versus 2.0, P < 0.05) and resistance index was lower in the adenosine group (0.70 versus 1.31 mm Hg per ml/min, P < 0.005)., Conclusions: Intracoronary adenosine accelerates recovery of microvascular perfusion in case of persistent ST segment elevation after primary PCI. more...
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- 2008
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20. Right coronary artery flow impairment in patients with pulmonary hypertension.
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van Wolferen SA, Marcus JT, Westerhof N, Spreeuwenberg MD, Marques KM, Bronzwaer JG, Henkens IR, Gan CT, Boonstra A, Postmus PE, and Vonk-Noordegraaf A
- Subjects
- Blood Flow Velocity, Blood Pressure physiology, Coronary Stenosis complications, Diastole, Female, Humans, Hypertension, Pulmonary etiology, Hypertrophy, Right Ventricular complications, Magnetic Resonance Angiography, Male, Middle Aged, Systole, Ventricular Dysfunction, Right complications, Coronary Circulation physiology, Coronary Stenosis physiopathology, Hypertension, Pulmonary physiopathology, Hypertrophy, Right Ventricular physiopathology, Ventricular Dysfunction, Right physiopathology
- Abstract
Aims: This study investigates whether increased right ventricular (RV) pressure in pulmonary hypertension (PH) impairs right coronary artery (RCA) flow and RV perfusion., Methods: In 25 subjects, five patients with idiopathic pulmonary arterial hypertension, nine patients with chronic thromboembolic pulmonary arterial hypertension, and 11 healthy controls, flow of the RCA and left anterior descending (LAD) artery was measured with MR flow quantification., Results: In PH, RCA peak systolic and mean systolic flow were lower, 1.02 +/- 0.62 mL/s and 0.42 +/- 0.30 mL/s, than peak and mean diastolic flow, 2.99 +/- 1.97 mL/s (P < 0.001) and 1.73 +/- 0.97 mL/s (P < 0.001); a pattern similar to the LAD. In contrast, in controls, RCA peak and mean flow in systole, 1.63 +/- 0.58 mL/s and 0.72 +/- 0.23 mL/s, were comparable to peak and mean flow in diastole, 1.72 +/- 0.48 mL/s and 0.93 +/- 0.28 mL/s (NS). The systolic-to-diastolic flow ratio in the RCA, and mean flow per gram RV tissue, were inversely related to RV mass, R = -0.61 (P = 0.009), and R = -0.73 (P < 0.001) and to RV pressure, R = -0.83 (P < 0.001), and R = -0.57 (P = 0.033)., Conclusion: Although in controls, RCA flow is similar in systole and diastole, in PH there is systolic flow impediment, which is proportional to RV pressure and mass. In patients with severe RV hypertrophy total mean flow is reduced. more...
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- 2008
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21. The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study.
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Bruynzeel AM, Niessen HW, Bronzwaer JG, van der Hoeven JJ, Berkhof J, Bast A, van der Vijgh WJ, and van Groeningen CJ
- Subjects
- Adult, Female, Heart Diseases chemically induced, Humans, Hydroxyethylrutoside therapeutic use, Male, Middle Aged, Myocytes, Cardiac drug effects, Myocytes, Cardiac pathology, Antibiotics, Antineoplastic adverse effects, Doxorubicin adverse effects, Heart Diseases prevention & control, Hydroxyethylrutoside analogs & derivatives, Neoplasms drug therapy
- Abstract
The purpose of this study was to investigate the cardioprotective effect of the semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER) on doxorubicin (DOX)-induced cardiotoxicity in a phase II study in patients with metastatic cancer. Eight patients with metastatic cancer were treated with DOX preceded by a 10 min i.v. infusion of 1500 mg m(-2) monoHER. Five patients were examined by endomyocardial biopsy after reaching a cumulative dose of 300 mg m(-2). Histopathological changes in the cardiomyocytes (Billingham score) were compared with those described in literature for patients treated with DOX only. The mean biopsy score of the patients was higher (2.7) than the mean score (1.4) of historical data of patients who received similar cumulative doses of DOX. Although there is a considerable variability in few investigated patients, it was indicative that monoHER enhanced DOX-induced cardiotoxicity. However, the antitumour activity of DOX seemed better than expected: three of the four patients with metastatic soft-tissue sarcoma had a partial remission and the fourth patient stable disease. It is likely that the relatively high dose of monoHER is responsible for the lack of cardioprotection and for the high response rate in patients with soft-tissue sarcoma possibly by depleting the glutathione defense system in both heart and tumour. more...
- Published
- 2007
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22. Effects of aging on left atrioventricular coupling and left ventricular filling assessed using cardiac magnetic resonance imaging in healthy subjects.
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Germans T, Götte MJ, Nijveldt R, Spreeuwenberg MD, Beek AM, Bronzwaer JG, Visser CA, Paulus WJ, and van Rossum AC
- Subjects
- Adult, Aged, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Aging, Atrial Function, Left physiology, Diastole physiology, Ventricular Function, Left physiology
- Abstract
Left ventricular (LV) filling results from diastolic suction of the left ventricle and passive left atrial (LA) emptying at early diastole and LA contraction at end-diastole. Effects of aging on LA and LV geometric characteristics and function and its consequences for LV filling are incompletely understood. Insight into these effects may increase the understanding of diastolic function. Cardiac magnetic resonance imaging was used to study effects of aging on left atrioventricular coupling and LV filling. Forty healthy volunteers underwent cardiac magnetic resonance imaging and were subdivided into 2 age groups of 20 to 40 (younger group) and 40 to 65 years (older group). For the older group, LA volumes were larger (p <0.05) and LV volumes, including stroke volumes, were smaller (p <0.05), whereas ejection fraction remained constant. LA/LV volume ratios were larger (0.27 +/- 0.06 vs 0.19 +/- 0.03; p <0.001) and correlated with LV mass-volume ratio (r = 0.42, p <0.01). The older group also had lower LA passive emptying (15 +/- 3.0 vs 19 +/- 4.8 ml/m(2); p <0.05) and higher LA active emptying volumes (13 +/- 3.1 vs 11 +/- 3.9 ml/m(2); p <0.05). For both groups, conduit volume contributed most to LV filling, but was lower in the older group (21 +/- 5.1 vs 27 +/- 9.0 ml; p <0.05). In conclusion, changes in LA volume and function were age dependent and related to changes in LV mass-volume ratio. Conduit volume contributed most to LV filling and decreased with age, suggesting it to be an indicator of diastolic function. more...
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- 2007
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23. Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients.
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Gan CT, Holverda S, Marcus JT, Paulus WJ, Marques KM, Bronzwaer JG, Twisk JW, Boonstra A, Postmus PE, and Vonk-Noordegraaf A
- Subjects
- Adult, Antihypertensive Agents therapeutic use, Blood Circulation physiology, Blood Pressure physiology, Bosentan, Epoprostenol therapeutic use, Female, Heart Ventricles pathology, Heart Ventricles physiopathology, Humans, Hypertension, Pulmonary physiopathology, Magnetic Resonance Imaging, Male, Middle Aged, Nitric Oxide therapeutic use, Purines therapeutic use, Severity of Illness Index, Sildenafil Citrate, Stroke Volume physiology, Sulfonamides therapeutic use, Vascular Resistance physiology, Hypertension, Pulmonary drug therapy, Piperazines therapeutic use, Sulfones therapeutic use, Vasodilator Agents therapeutic use, Ventricular Dysfunction, Right physiopathology
- Abstract
Aims: This study investigated whether right ventricular (RV) diastolic function is impaired in pulmonary hypertension (PH) patients, and whether it is related to RV mass and afterload. In addition, the effects of an acute reduction of RV afterload by the oral intake of sildenafil were studied. Finally, we assessed whether diastolic function is related to cardiac parameters of disease severity., Methods and Results: Twenty-five PH patients and 11 control subjects were studied. Right-heart catheterization and N-terminal pro-brain natriuretic peptide (NT-proBNP) sampling were performed in patients. MRI measured RV ejection fraction, mass, and diastolic function. Isovolumic relaxation time (IVRT), normalized early peak filling rate (E), atrium-induced peak filling rate (A), and E/A ratio described diastolic function. Compared to control subjects, patients had prolonged mean (+/- SD) IVRT (133.5 +/- 53.2 vs 29.3 +/- 20.8 ms, respectively; p < 0.001), decreased E (3.0 +/- 1.6 vs 6.4 +/- 2.5 s(-1), respectively; p < 0.001) and E/A ratio (1.1 +/- 0.7 vs 5.3 +/- 4.9, respectively; p < 0.001), and increased A (3.0 +/- 1.4 vs 1.5 +/- 0.9 s(-1), respectively; p = 0.001). IVRT was related to RV mass (r(25) = 0.56; p = 0.005) and pulmonary vascular resistance (r(25) = 0.74; p < 0.0001). Sildenafil therapy reduced RV afterload and improved RV diastolic and systolic function. IVRT was correlated with NT-proBNP level (r = 0.70; p < 0.001), and was inversely related to cardiac index (r = -0.70; p < 0.001) and RV ejection fraction (r = -0.69; p < 0.001)., Conclusion: In PH patients, RV diastolic dysfunction is related to RV mass and afterload. RV diastolic function improves by reducing afterload. The correlations between diastolic function and prognostic parameters showed that diastolic function is most impaired in patients with severe disease. more...
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- 2007
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24. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension.
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van Wolferen SA, Marcus JT, Boonstra A, Marques KM, Bronzwaer JG, Spreeuwenberg MD, Postmus PE, and Vonk-Noordegraaf A
- Subjects
- Adult, Cardiac Catheterization, Exercise Test, Female, Follow-Up Studies, Heart Ventricles physiopathology, Humans, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary physiopathology, Magnetic Resonance Imaging, Cine, Male, Prognosis, Pulmonary Artery physiopathology, Risk Factors, Stroke Volume, Survival Analysis, Hypertension, Pulmonary mortality, Ventricular Dysfunction, Left diagnosis, Ventricular Dysfunction, Right diagnosis
- Abstract
Aims: This study investigated the relationship between right ventricular (RV) structure and function and survival in idiopathic pulmonary arterial hypertension (IPAH)., Methods and Results: In 64 patients, cardiac magnetic resonance, right heart catheterization, and the six-minute walk test (6MWT) were performed at baseline and after 1-year follow-up. RV structure and function were analysed as predictors of mortality. During a mean follow-up of 32 months, 19 patients died. A low stroke volume (SV), RV dilatation, and impaired left ventricular (LV) filling independently predicted mortality. In addition, a further decrease in SV, progressive RV dilatation, and further decrease in LV end-diastolic volume (LVEDV) at 1-year follow-up were the strongest predictors of mortality. According to Kaplan-Meier survival curves, survival was lower in patients with an inframedian SV index
or= 84 mL/m(2), and an inframedian LVEDV more...- Published
- 2007
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25. Right ventricular reverse remodelling after sildenafil in pulmonary arterial hypertension.
- Author
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van Wolferen SA, Boonstra A, Marcus JT, Marques KM, Bronzwaer JG, Postmus PE, and Vonk-Noordegraaf A
- Subjects
- Female, Humans, Hypertension, Pulmonary blood, Hypertension, Pulmonary physiopathology, Male, Natriuretic Peptide, Brain metabolism, Peptide Fragments metabolism, Purines, Sildenafil Citrate, Sulfones, Ventricular Remodeling, Hypertension, Pulmonary drug therapy, Piperazines therapeutic use, Vasodilator Agents therapeutic use
- Published
- 2006
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26. Myocardial structure and function differ in systolic and diastolic heart failure.
- Author
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van Heerebeek L, Borbély A, Niessen HW, Bronzwaer JG, van der Velden J, Stienen GJ, Linke WA, Laarman GJ, and Paulus WJ
- Subjects
- Aged, Biopsy, Cardiomegaly pathology, Female, Heart Failure physiopathology, Humans, Male, Middle Aged, Myocytes, Cardiac pathology, Myocytes, Cardiac physiology, Diastole physiology, Heart Failure pathology, Heart Ventricles pathology, Systole physiology
- Abstract
Background: To support the clinical distinction between systolic heart failure (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial structure and function were compared in LV endomyocardial biopsy samples of patients with systolic and diastolic heart failure., Methods and Results: Patients hospitalized for worsening heart failure were classified as having SHF (n=22; LV ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had coronary artery disease or biopsy evidence of infiltrative or inflammatory myocardial disease. More DHF patients had a history of arterial hypertension and were obese. Biopsy samples were analyzed with histomorphometry and electron microscopy. Single cardiomyocytes were isolated from the samples, stretched to a sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated with calcium-containing solutions to measure total force. Cardiomyocyte diameter was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/-2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable. After administration of protein kinase A to the cardiomyocytes, the drop in Fpassive was larger (P<0.01) in DHF than in SHF., Conclusions: LV myocardial structure and function differ in SHF and DHF because of distinct cardiomyocyte abnormalities. These findings support the clinical separation of heart failure patients into SHF and DHF phenotypes. more...
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- 2006
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27. Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension.
- Author
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Gan C, Lankhaar JW, Marcus JT, Westerhof N, Marques KM, Bronzwaer JG, Boonstra A, Postmus PE, and Vonk-Noordegraaf A
- Subjects
- Adult, Female, Humans, Hypertension, Pulmonary complications, Hypertension, Pulmonary diagnosis, Male, Middle Aged, Ventricular Dysfunction diagnosis, Ventricular Dysfunction etiology, Hypertension, Pulmonary physiopathology, Pulmonary Artery physiopathology, Stroke Volume, Ventricular Dysfunction physiopathology
- Abstract
The aim of this study was to investigate the contribution of direct right-to-left ventricular interaction to left ventricular filling and stroke volume in 46 patients with pulmonary arterial hypertension (PAH) and 18 control subjects. Stroke volume, right and left ventricular volumes, left ventricular filling rate, and interventricular septum curvature were measured by magnetic resonance imaging and left atrial filling by transesophageal echocardiography. Stroke volume, left ventricular end-diastolic volume, and left ventricular peak filling rate were decreased in PAH patients compared with control subjects: 28 +/- 13 vs. 41 +/- 10 ml/m(2) (P < 0.001), 46 +/- 14 vs. 61 +/- 14 ml/m(2) (P < 0.001), and 216 +/- 90 vs. 541 +/- 248 ml/s (P < 0.001), respectively. Among PAH patients, stroke volume did not correlate to right ventricular end-diastolic volume or mean pulmonary arterial pressure but did correlate to left ventricular end-diastolic volume (r = 0.62, P < 0.001). Leftward interventricular septum curvature was correlated to left ventricular filling rate (r = 0.64, P < 0.001) and left ventricular end-diastolic volume (r = 0.65, P < 0.001). In contrast, left atrial filling was normal and not correlated to left ventricular end-diastolic volume. In PAH patients, ventricular interaction mediated by the interventricular septum impairs left ventricular filling, contributing to decreased stroke volume. more...
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- 2006
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28. Functional effects of protein kinase C-mediated myofilament phosphorylation in human myocardium.
- Author
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van der Velden J, Narolska NA, Lamberts RR, Boontje NM, Borbély A, Zaremba R, Bronzwaer JG, Papp Z, Jaquet K, Paulus WJ, and Stienen GJ
- Subjects
- Adult, Biomechanical Phenomena, Calcium metabolism, Case-Control Studies, Cells, Cultured, Cyclic AMP-Dependent Protein Kinases pharmacology, Electrophoresis, Gel, Two-Dimensional, Female, Humans, Male, Middle Aged, Phosphorylation, Protein Kinase C pharmacology, Troponin I metabolism, Actin Cytoskeleton metabolism, Cardiomyopathy, Dilated enzymology, Myocytes, Cardiac metabolism, Protein Kinase C metabolism
- Abstract
Objective: In human heart failure beta-adrenergic-mediated protein kinase A (PKA) activity is down-regulated, while protein kinase C (PKC) activity is up-regulated. PKC-mediated myofilament protein phosphorylation might be detrimental for contractile function in cardiomyopathy. This study was designed to reveal the effects of PKC on myofilament function in human myocardium under basal conditions and upon modulation of protein phosphorylation by PKA and phosphatases., Methods: Isometric force was measured at different [Ca(2+)] in single permeabilized cardiomyocytes from non-failing and failing human left ventricular tissue. Basal phosphorylation of myofilament proteins and the influence of PKC, PKA, and phosphatase treatments were analyzed by one- and two-dimensional gel electrophoresis, Western immunoblotting, and ELISA., Results: Troponin I (TnI) phosphorylation at the PKA sites was decreased in failing compared to non-failing hearts and correlated well with myofilament Ca(2+) sensitivity (pCa(50)). Incubation with the catalytic domain of PKC slightly decreased maximal force under basal conditions, but not following PKA and phosphatase pretreatments. PKC reduced Ca(2+) sensitivity to a larger extent in failing (DeltapCa(50)=0.19+/-0.03) than in non-failing (DeltapCa(50)=0.08+/-0.01) cardiomyocytes. This shift was reduced, though still significant, when PKC was preceded by PKA, while PKA following PKC did not further decrease pCa(50). Protein analysis indicated that PKC phosphorylated PKA sites in human TnI and increased phosphorylation of troponin T, while myosin light chain phosphorylation remained unaltered., Conclusion: In human myocardium PKC-mediated myofilament protein phosphorylation only has a minor effect on maximal force development. The PKC-mediated decrease in Ca(2+) sensitivity may serve to improve diastolic function in failing human myocardium in which PKA-mediated TnI phosphorylation is decreased. more...
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- 2006
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29. Dutch guidelines for interventional cardiology: institutional and operator competence and requirements for training.
- Author
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Aengevaeren WR, Laarman GJ, Suttorp MJ, Ten Berg JM, van Boven AJ, de Boer MJ, Piek JJ, van Ommen GV, Bronzwaer JG, Smits P, and Deckers JW
- Abstract
Interventional cardiology is an expanding field within cardiovascular medicine and today it is generally accepted that cardiologists require specific training, knowledge and skills. Hospitals where coronary interventions are performed must be properly equipped and able to provide specialised care. Percutaneous coronary interventions are frequently used for coronary revascularisation. The public should have confidence in the uniformity of high quality care. Therefore, such quality of care should be maintained by certification of the individual operators, general guidelines for institutional requirements and formal audits. The Netherlands Society of Cardiology (NVVC) will be implementing a new registration system for cardiologists with a subspecialisation that will include registration for interventional cardiology. The NVVC asked the Working Group of Interventional Cardiology (WIC) to update the 1994 Dutch guidelines on operator and institutional competence, and requirements for training in interventional cardiology in order to incorporate them into the official directives. The present guidelines represent the expert opinion of the Dutch interventional cardiology community and are in accordance with international regulations. After two rounds of discussion, the NVVC approved the guidelines in November 2004 during the autumn meeting. more...
- Published
- 2005
30. A comparison of noninvasive MRI-based methods of estimating pulmonary artery pressure in pulmonary hypertension.
- Author
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Roeleveld RJ, Marcus JT, Boonstra A, Postmus PE, Marques KM, Bronzwaer JG, and Vonk-Noordegraaf A
- Subjects
- Catheterization, Echocardiography, Doppler, Humans, Blood Pressure physiology, Hypertension, Pulmonary physiopathology, Magnetic Resonance Imaging methods, Pulmonary Artery physiopathology
- Abstract
Purpose: To assess the accuracy of several noninvasive MRI-based estimators of pulmonary artery pressure by comparing them with invasive pressure measurement., Materials and Methods: We compared five MRI methods with invasive pressure measurement by catheterization, in one group of pulmonary hypertension (PH) patients. Doppler echocardiography was included as a reference method. Main inclusion criterion was a mean pulmonary artery pressure above 25 mmHg at catheterization. MRI velocity quantification was used to obtain pulmonary flow acceleration and ejection times, and pulse wave velocity. The ventricular mass index was also assessed on MRI. Two commercially available 1.5-T systems were used for this study., Results: Data from 44 patients were analyzed. Correlation of acceleration time with mean pressure was: r = -0.21, P = 0.21, correlation of the acceleration/ejection time ratio with systolic pressure was: r = -0.26, P = 0.01. The ventricular mass index showed the best correlation with mean pressure, with r = 0.56, P < 0.001. Using the pulse wave velocity and the cross-sectional area of the pulmonary artery, the mean pressure could not be estimated accurately., Conclusion: Accurate estimation of pulmonary artery pressure in PH patients was not feasible by the MRI estimators studied. These noninvasive methods cannot replace right heart catheterization at this moment. more...
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- 2005
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31. Cardiomyocyte stiffness in diastolic heart failure.
- Author
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Borbély A, van der Velden J, Papp Z, Bronzwaer JG, Edes I, Stienen GJ, and Paulus WJ
- Subjects
- Aged, Aged, 80 and over, Calcium metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Female, Hemodynamics physiology, Humans, Male, Middle Aged, Myocardium pathology, Myocytes, Cardiac enzymology, Stroke Volume physiology, Ventricular Function, Left physiology, Ventricular Pressure physiology, Diastole physiology, Heart Failure pathology, Myocytes, Cardiac pathology
- Abstract
Background: Heart failure with preserved left ventricular (LV) ejection fraction (EF) is increasingly recognized and usually referred to as diastolic heart failure (DHF). Its pathogenetic mechanism remains unclear, partly because of a lack of myocardial biopsy material. Endomyocardial biopsy samples obtained from DHF patients were therefore analyzed for collagen volume fraction (CVF) and sarcomeric protein composition and compared with control samples. Single cardiomyocytes were isolated from these biopsy samples to assess cellular contractile performance., Methods and Results: DHF patients (n=12) had an LVEF of 71+/-11%, an LV end-diastolic pressure (LVEDP) of 28+/-4 mm Hg, and no significant coronary artery stenoses. DHF patients had higher CVFs (7.5+/-4.0%, P<0.05) than did controls (n=8, 3.8+/-2.0%), and no conspicuous changes in sarcomeric protein composition were detected. Cardiomyocytes, mechanically isolated and treated with Triton X-100 to remove all membranes, were stretched to a sarcomere length of 2.2 microm and activated with solutions containing varying [Ca2+]. Compared with cardiomyocytes of controls, cardiomyocytes of DHF patients developed a similar total isometric force at maximal [Ca2+], but their resting tension (F(passive)) in the absence of Ca2+ was almost twice as high (6.6+/-3.0 versus 3.5+/-1.7 kN/m2, P<0.001). F(passive) and CVF combined yielded stronger correlations with LVEDP than did either alone. Administration of protein kinase A (PKA) to DHF cardiomyocytes lowered F(passive) to control values., Conclusions: DHF patients had stiffer cardiomyocytes, as evident from a higher F(passive) at the same sarcomere length. Together with CVF, F(passive) determined in vivo diastolic LV dysfunction. Correction of this high F(passive) by PKA suggests that reduced phosphorylation of sarcomeric proteins is involved in DHF. more...
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- 2005
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32. Matrix, cytoskeleton, or myofilaments: which one to blame for diastolic left ventricular dysfunction?
- Author
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Bronzwaer JG and Paulus WJ
- Subjects
- Calcium metabolism, Connectin, Cytoskeleton physiology, Diastole physiology, Electrocardiography, Heart Failure metabolism, Heart Failure physiopathology, Humans, Muscle Proteins metabolism, Myocardial Contraction physiology, Protein Kinases metabolism, Ventricular Dysfunction, Left metabolism, Actin Cytoskeleton physiology, Cytoskeletal Proteins physiology, Extracellular Matrix physiology, Ventricular Dysfunction, Left etiology
- Abstract
During cardiac filling, the relative contribution of distension of interstitial collagen, of distension of cytoskeletal proteins, and of low-grade diastolic cross-bridge cycling in the generation of diastolic left ventricular (LV) pressure remains unclear. In failing myocardium, interstitial collagen deposition and cross-linking are augmented. This increase in collagen deposition is accompanied by expression of a stiffer isoform of titin in the cardiomyocytes. Higher diastolic stiffness of failing myocardium is therefore not necessarily related to increased interstitial collagen content. Moreover, phosporylation of titin by protein kinase A and G, and inhibition of titin-actin interaction by cytosolic calcium allow for dynamic modulation of its diastolic tension generation and could account for acute shifts of myocardial distensibility. Acute shifts of myocardial distensibility, as occur in hypertrophy or in demand ischemia, have usually been attributed to a diastolic resurgence of cross-bridge interaction. In hypertrophied and failing myocardium, the recent demonstrations of diastolic calcium release from the ryanodine receptor, of deficient diastolic calcium removal from the cytosol, and of enhanced myofilamentary calcium sensitivity support residual diastolic cross-bridge interaction. In demand ischemia, the role of calcium overload in the reduction of diastolic LV distensibility is less clear because of correction of the reduced diastolic LV distensibility by quick stretches but not by a calcium desensitizer. Simultaneous imposition in animal models of multiple molecular changes involving interstitial, cytoskeletal, and myofilamentary proteins could elucidate their relative importance for myocardial stiffness and lead to selective correction of diastolic LV dysfunction as a novel mode of heart-failure therapy. more...
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- 2005
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33. Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial).
- Author
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van Loon RB, Veen G, Kamp O, Bronzwaer JG, Visser CA, and Visser FC
- Abstract
BACKGROUND: Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery.Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. METHODS: The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care).The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. CONCLUSION: The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction. more...
- Published
- 2004
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34. A review of pulmonary arterial hypertension: Part 2: Current and expected treatments.
- Author
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Gan CT, Noordegraaf AV, Marques KM, Bronzwaer JG, Postmus PE, and Boonstra A
- Abstract
Medical therapy for pulmonary arterial hypertension (PAH) focuses on pulmonary vascular remodelling and smooth muscle cell proliferation. This article covers the drugs which are approved or are in sight and the evidence-based treatment strategies that target the different pathobiological pathways, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice, June 2003. In addition we briefly look at the 'Venice consensus' on surgical treatment. In the past five and a half years more than 360 patients were seen for pulmonary hypertension in the Free University Medical Centre (VUmc). Present-day treatment, research studies and novel treatment strategies in the VUmc will be reviewed. Future treatments will be on the basis of insights into pathobiology, pathogenesis and genes in PAH and should focus on drug combinations, which theoretically target different or similar pathobiological pathways. more...
- Published
- 2004
35. Nitric oxide's role in the heart: control of beating or breathing?
- Author
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Paulus WJ and Bronzwaer JG
- Subjects
- Animals, Diastole, Energy Metabolism, Humans, Isometric Contraction, Myocardium metabolism, Stress, Physiological physiopathology, Heart physiology, Heart physiopathology, Myocardial Contraction physiology, Nitric Oxide metabolism, Respiratory Physiological Phenomena
- Abstract
Beneficial actions of nitric oxide (NO) in failing myocardium have frequently been overshadowed by poorly documented negative inotropic effects mainly derived from in vitro cardiac preparations. NO's beneficial actions include control of myocardial energetics and improvement of left ventricular (LV) diastolic distensibility. In isolated cardiomyocytes, administration of NO increases their diastolic cell length consistent with a rightward shift of the passive length-tension relation. This shift is explained by cGMP-induced phosphorylation of troponin I, which prevents calcium-independent diastolic cross-bridge cycling and concomitant diastolic stiffening of the myocardium. Similar improvements in diastolic stiffness have been observed in isolated guinea pig hearts, in pacing-induced heart failure dogs, and in patients with dilated cardiomyopathy or aortic stenosis and have been shown to result in higher LV preload reserve and stroke work. NO also controls myocardial energetics through its effects on mitochondrial respiration, oxygen consumption, and substrate utilization. The effects of NO on diastolic LV performance appear to be synergistic with its effects on myocardial energetics through prevention of myocardial energy wastage induced by LV contraction against late-systolic reflected arterial pressure waves and through prevention of diastolic LV stiffening, which is essential for the maintenance of adequate subendocardial coronary perfusion. A drop in these concerted actions of NO on diastolic LV distensibility and on myocardial energetics could well be instrumental for the relentless deterioration of failing myocardium. more...
- Published
- 2004
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36. What mechanisms underlie diastolic dysfunction in heart failure?
- Author
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Kass DA, Bronzwaer JG, and Paulus WJ
- Subjects
- Adult, Aged, Biomechanical Phenomena, Calcium Signaling, Connectin, Elasticity, Female, Fibrosis, Heart Failure classification, Heart Failure epidemiology, Humans, Male, Middle Aged, Muscle Proteins physiology, Muscle Relaxation, Myocardial Contraction, Myocardium pathology, Myocytes, Cardiac physiology, Protein Kinases physiology, Diastole physiology, Heart Failure physiopathology
- Abstract
Abnormalities of diastolic function are common to virtually all forms of cardiac failure. However, their underlying mechanisms, precise role in the generation and phenotypic expression of heart failure, and value as specific therapeutic targets remain poorly understood. A growing proportion of heart failure patients, particularly among the elderly, have apparently preserved systolic function, and this is fueling interest for better understanding and treating diastolic abnormalities. Much of the attention in clinical and experimental studies has focused on relaxation and filling abnormalities of the heart, whereas chamber stiffness has been less well studied, particularly in humans. Nonetheless, new insights from basic and clinical research are helping define the regulators of diastolic dysfunction and illuminate novel targets for treatment. This review puts these developments into perspective with the major aim of highlighting current knowledge gaps and controversies. more...
- Published
- 2004
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37. A review of pulmonary arterial hypertension: Part 1. Novel insights and classification.
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Gan CT, Noordegraaf AV, Marques KM, Bronzwaer JG, Postmus PE, and Boonstra A
- Abstract
Pulmonary arterial hypertension (PAH) is a disease characterised by an increased pulmonary artery pressure. The precapillary pulmonary arteries show distinct pathobiological changes, i.e. medial hypertrophy, intimal fibrosis, microthrombi and plexiform lesions. Although the pathogenesis is not completely understood, pulmonary vascular proliferation and remodelling, due to a variety of mediators, is believed to play the pathogenetic key role. Genetic research reveals molecular deformities and gene mutations associated with phenotypic PAH. This article covers novel insights into pathobiology, pathogenesis and genes of PAH, which led to a novel classification system and a diagnostic work-up, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice in June 2003. more...
- Published
- 2004
38. Effects of epoprostenol on right ventricular hypertrophy and dilatation in pulmonary hypertension.
- Author
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Roeleveld RJ, Vonk-Noordegraaf A, Marcus JT, Bronzwaer JG, Marques KM, Postmus PE, and Boonstra A
- Subjects
- Adult, Aged, Blood Flow Velocity drug effects, Case-Control Studies, Dilatation, Pathologic, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Heart Function Tests, Humans, Hypertension, Pulmonary complications, Hypertension, Pulmonary diagnosis, Hypertrophy, Right Ventricular complications, Magnetic Resonance Imaging, Male, Middle Aged, Probability, Prospective Studies, Reference Values, Statistics, Nonparametric, Treatment Outcome, Ventricular Remodeling drug effects, Antihypertensive Agents administration & dosage, Epoprostenol administration & dosage, Hypertension, Pulmonary drug therapy, Hypertrophy, Right Ventricular diagnosis, Ventricular Function, Right drug effects
- Abstract
Objectives: To gain more knowledge of changes in main pulmonary artery flow and right ventricular mass and volumes in patients with pulmonary hypertension during epoprostenol therapy., Methods: Eleven patients (9 women) were evaluated before the start of therapy and every 4 months thereafter. Right and left ventricular volumes and masses were measured by cine MRI. Flow was measured with MRI velocity quantification. At the same times, 6-min walking tests were performed. Right-heart catheterizations were performed at baseline and after 1 year., Results: Right ventricular mass in the patient group was significantly higher from that in a control group of healthy volunteers (95 +/- 26 g vs 42 +/- 10 g, p < 0.05 [mean +/- SD]), whereas the stroke volume was lower (34 +/- 11 mL vs 81 +/- 11 mL, p < 0.05). The greatest improvement in right ventricular stroke volume (to 41 +/- 11 mL, p < 0.05) took place in the first 4 months. During the 1-year follow-up, right ventricular end-diastolic volume and mass did not change, and mean pulmonary artery pressure remained nearly stable at 55 mm Hg at baseline and 53 mm Hg after 1 year. Pulmonary vascular resistance decreased by 12.5% (p = 0.06)., Conclusions: From these data we conclude that epoprostenol lowers pulmonary vascular resistance, leading to an increase in pulmonary artery flow. This increase in pulmonary artery flow corresponds well with the increase in 6-min walking distance and can be noninvasively monitored by MRI (flow quantification). Right ventricular dilatation and hypertrophy are not reversed by epoprostenol therapy, but do not progress either. more...
- Published
- 2004
- Full Text
- View/download PDF
39. [Diagnosis of pulmonary hypertension: experiences with 187 patients referred to the VU Medical Center].
- Author
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Roeleveld RJ, Boonstra AB, Voskuyl AE, Bronzwaer JG, Marques KM, and vonk Noordegraaf A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Connective Tissue Diseases complications, Connective Tissue Diseases diagnosis, Diagnosis, Differential, Diagnostic Errors, Female, Heart Septal Defects, Atrial complications, Heart Septal Defects, Atrial diagnosis, Humans, Hypertension, Pulmonary etiology, Male, Middle Aged, Referral and Consultation, Retrospective Studies, Thromboembolism complications, Thromboembolism diagnosis, Ventricular Dysfunction, Left complications, Ventricular Dysfunction, Left diagnosis, Hypertension, Pulmonary diagnosis
- Abstract
Objective: To describe the results of a multidisciplinary diagnostic protocol in patients referred due to suspected pulmonary hypertension., Design: Descriptive., Method: In 187 patients who were referred to the VU Medical Centre, Amsterdam, the Netherlands, between May 1998 and February 2003, due to suspected pulmonary hypertension, the diagnosis was established by means of a multidisciplinary diagnostic protocol. The referral and final diagnoses were analysed, as well as the treatment the patients had received., Results: In 56 patients (30%), the application of the protocol lead to a modification of the diagnosis; 16 patients (9%) were found not to have pulmonary hypertension; in 20 of the 89 patients referred with 'primary pulmonary hypertension' (48% of all referrals), an underlying disease was still identified: 6 cases of a connective tissue disease, 5 cases of a chronic thromboembolic process, 5 cases of a condition of the left heart, and 4 cases of an atrial septal defect., Conclusion: The diagnosis 'primary pulmonary hypertension' can only be made once all secondary types of the disease have been ruled out. The application of a multidisciplinary diagnostic protocol together with a contribution of specialists with specific expertise can help to adjust the initial diagnosis and sometimes even reject it. more...
- Published
- 2004
40. [Diastolic heart failure].
- Author
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Smulders YM, Stehouwer CD, Bronzwaer JG, and Kamp O
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Age Factors, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Digoxin adverse effects, Digoxin therapeutic use, Echocardiography, Heart Failure drug therapy, Heart Failure mortality, Humans, Hypertension complications, Obesity complications, Prognosis, Diastole physiology, Heart Failure diagnosis
- Abstract
Diastolic heart failure is predominantly a disease of the elderly: at the age of 70 years, almost half of all patients with heart failure have diastolic heart failure. Hypertension and obesity are common underlying disorders in patients with diastolic heart failure. Patients with diastolic heart failure have an equal, or only slightly better, prognosis in terms of mortality compared to patients with systolic heart failure. Echocardiography can distinguish diastolic heart failure from systolic heart failure. Patients with heart failure and a normal ejection fraction almost certainly have a diastolic dysfunction. There is a lack of reliable data about the optimal medicinal treatment strategy for patients with diastolic heart failure. Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and (non-dihydropyridine) calcium antagonists have therapeutic potential. Digoxin may be contraindicated. more...
- Published
- 2003
41. Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy.
- Author
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Bronzwaer JG, Heymes C, Visser CA, and Paulus WJ
- Subjects
- Adult, Aged, Elasticity, Female, Fibrosis, Humans, Male, Middle Aged, Cardiomyopathy, Dilated physiopathology, Myocardium pathology, Nitric Oxide Synthase metabolism, Ventricular Function, Left
- Abstract
The purpose of the study was to investigate interactions between myocardial nitric oxide synthase (NOS) and myocardial fibrosis, both of which determine left ventricular (LV) preload reserve in patients with nonischemic dilated cardiomyopathy (DCM). In previous animal experiments, chronic inhibition of NOS induced myocardial fibrosis and limited LV preload reserve. Twenty-eight DCM patients underwent LV catheterization, balloon caval occlusions (BCO; n = 8), intracoronary substance P infusion (n = 8), and procurement of LV endomyocardial biopsies for determinations of collagen volume fraction (CVF), of gene expression of NOS2, NOS3, heme oxygenase (HO)-1, and TNF-alpha, and of NOS2 protein. CVF was unrelated to the intensity of NOS2, NOS3, HO-1, or TNF-alpha gene expression or of NOS2 protein expression. Preload recruitable LV stroke work (PR-LVSW) correlated directly with NOS2 gene expression (P = 0.001) and inversely with CVF (P = 0.04). High CVF (>10%) reduced baseline LVSW and PR-LVSW at each level of NOS2 gene expression. In DCM, myocardial fibrosis is unrelated to the intensity of myocardial gene expression of NOS, antioxidative enzymes (HO-1), or cytokines (TNF-alpha) and blunts NOS2-related recruitment of LV preload reserve. more...
- Published
- 2003
- Full Text
- View/download PDF
42. Assessment of coronary artery bypass graft disease using cardiovascular magnetic resonance determination of flow reserve.
- Author
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Bedaux WL, Hofman MB, Vyt SL, Bronzwaer JG, Visser CA, and van Rossum AC
- Subjects
- Adult, Aged, Anastomosis, Surgical, Arteries physiopathology, Arteries surgery, Coronary Angiography, Coronary Stenosis diagnosis, Coronary Stenosis physiopathology, Coronary Stenosis surgery, Coronary Vessels physiopathology, Coronary Vessels surgery, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Saphenous Vein diagnostic imaging, Saphenous Vein surgery, Sensitivity and Specificity, Ultrasonography, Blood Flow Velocity physiology, Coronary Artery Bypass, Magnetic Resonance Imaging
- Abstract
Objectives: The purpose of this study was to assess the value of cardiovascular magnetic resonance (CMR)-determined graft flow and flow reserve in differentiating significant from non-significant vein graft disease., Background: In patients after coronary artery bypass grafting (CABG), non-invasive testing may be helpful in the detection of recurrent graft disease., Methods: Randomly selected patients (n = 21) scheduled for X-ray angiography because of recurrent chest complaints after CABG were included for evaluation of vein grafts (n = 40) by CMR. Three-dimensional contrast-enhanced CMR angiography was performed and followed by flow measurements at rest and during hyperemia in patent grafts only. Flow reserve was calculated when resting flow exceeded 20 ml/min. Analysis was based on four categories defined by X-ray angiography: occluded grafts (n = 3), grafts with stenosis >50% (n = 19), grafts with stenosis <50% with diseased graft run-off (n = 8), and grafts with stenosis <50% and normal run-off (n = 10)., Results: The CMR angiography demonstrated occlusion of three grafts. In nine of the 37 patent grafts, basal blood flow was <20 ml/min, all demonstrating significant stenosis at X-ray angiography. In grafts with resting flow >20 ml/min (n = 28), flow reserve significantly differed between grafts without stenosis and grafts with significant stenosis or with diseased run-off (2.5 +/- 0.7 vs. 1.8 +/- 0.9, p = 0.04). An algorithm combining basal volume flow <20 ml/min and graft flow reserve <2 had a sensitivity and specificity of 78% and 80% respectively for detecting grafts with significant stenosis or diseased run-off., Conclusions: This feasibility study showed that quantification of flow and flow reserve by CMR may serve as a non-invasive adjunct to differentiate between vein grafts without stenosis and grafts with significant stenosis or diseased run-off. more...
- Published
- 2002
- Full Text
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43. Myocardial contractile effects of nitric oxide.
- Author
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Paulus WJ and Bronzwaer JG
- Subjects
- Animals, Hypertrophy, Left Ventricular physiopathology, Mice, Systole, Hypertrophy, Left Ventricular metabolism, Myocardial Contraction physiology, Nitric Oxide metabolism, Ventricular Function, Left physiology
- Abstract
Recent experimental and clinical research solved some of the controversies surrounding the myocardial contractile effects of NO. These controversies were: (1) does NO exert a contractile effect at baseline? (2) is NO a positive or a negative inotrope? (3) Are the contractile effects of NO similar when NO is derived from NO-donors or from the different isoforms of NO synthases (NOS)? (4) Does NO exert the same effects in hypertrophied, failing or ischemic myocardium? Transgenic mice with cardioselective overexpression of NOS revealed NO to produce a small reduction in basal developed LV pressure and a LV relaxation-hastening effect mainly through myofilamentary desensitization. Similar findings had previously been reported during intracoronary infusions of NO-donors in isolated rodent hearts and in humans. The LV relaxation hastening effect was accompanied by increased diastolic LV distensibility, which augmented LV preload reserve especially in heart failure patients. This beneficial effect on diastolic LV function always overrode the small NO-induced attenuation in LV developed pressure in terms of overall LV performance. In most experimental and clinical conditions, contractile effects of NO were similar when NO was derived from NO-donors or produced by the different isoforms of NOS. Because expression of inducible NOS (NOS2) is frequently accompanied by elevated oxidative stress, NO produced by NOS2 can lead to peroxynitrite-induced contractile impairment as observed in ischemic or septic myocardium. Finally, shifts in isoforms or in concentrations of myofilaments can affect NO-mediated myofilamentary desensitization and alter the myocardial contractile effects of NO in hypertrophied or failing myocardium. more...
- Published
- 2002
- Full Text
- View/download PDF
44. Endomyocardial nitric oxide synthase and the hemodynamic phenotypes of human dilated cardiomyopathy and of athlete's heart.
- Author
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Bronzwaer JG, Zeitz C, Visser CA, and Paulus WJ
- Subjects
- Adult, Aged, Cardiomyopathy, Dilated physiopathology, Exercise physiology, Female, Gene Expression, Hemodynamics, Humans, Male, Middle Aged, Nitric Oxide Synthase genetics, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Phenotype, Reverse Transcriptase Polymerase Chain Reaction, Ventricular Function, Left physiology, Bicycling, Cardiomyopathy, Dilated enzymology, Nitric Oxide Synthase physiology, Pericardium enzymology
- Abstract
Objective: In dilated cardiomyopathy and in athlete's heart, progressive LV dilatation is accompanied by rightward displacement of the diastolic LV pressure-volume relation. In dilated cardiomyopathy, an increase in diastolic LV stiffness can limit this rightward displacement thereby decreasing LV systolic performance. Because nitric oxide (NO) reduces diastolic LV stiffness, the present study relates diastolic LV stiffness and LV systolic performance to intensity of endomyocardial NO synthase (NOS) gene expression in dilated cardiomyopathy and in athlete's heart., Methods: Microtip LV pressures, conductance-catheter or angiographic LV volumes, echocardiographic LV wall thicknesses and snap-frozen LV endomyocardial biopsies were obtained in 33 patients with dilated cardiomyopathy and in three professional cyclists referred for sustained ventricular tachycardia. Intensity of LV endomyocardial inducible NOS (NOS2) and constitutive NOS (NOS3) gene expression was determined using quantitative reverse transcription-polymerase chain reaction (RT-PCR)., Results: Dilated cardiomyopathy patients with higher diastolic LV stiffness-modulus and lower LV stroke work had lower NOS2 and NOS3 gene expression at any given level of LV end-diastolic wall stress. The intensity of NOS2 and NOS3 gene expression observed in athlete's heart was similar to dilated cardiomyopathy with low LV diastolic stiffness-modulus and preserved LV stroke work., Conclusions: High LV endomyocardial NOS gene expression is observed in athlete's heart and in dilated cardiomyopathy with low diastolic LV stiffness and preserved LV stroke work. Favourable effects on the hemodynamic phenotype of high LV endomyocardial NOS gene expression could result from a NO-mediated decrease in diastolic LV stiffness and a concomitant rise in LV preload reserve. more...
- Published
- 2002
- Full Text
- View/download PDF
45. Epoprostenol-induced pulmonary vasodilatation in patients with pulmonary hypertension measured by electrical impedance tomography.
- Author
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Smit HJ, Vonk Noordegraaf A, Roeleveld RJ, Bronzwaer JG, Postmus PE, de Vries PM, and Boonstra A
- Subjects
- Adult, Aged, Female, Heart physiopathology, Hemodynamics drug effects, Hemodynamics physiology, Humans, Male, Middle Aged, Pulmonary Artery drug effects, Pulmonary Artery physiology, Pulmonary Wedge Pressure drug effects, Pulmonary Wedge Pressure physiology, Antihypertensive Agents therapeutic use, Electric Impedance, Epoprostenol therapeutic use, Hypertension, Pulmonary drug therapy, Hypertension, Pulmonary pathology, Pulmonary Circulation drug effects, Tomography methods, Vasodilation drug effects
- Abstract
Electrical impedance tomography (EIT) has been proposed as a method to monitor dynamic changes in the pulmonary vascular bed. In this study we examined the validity of EIT in the measurement of pulmonary vasodilatation in eight patients with primary and secondary pulmonary hypertension when given the vasodilating agent epoprostenol (Flolan). Therefore, catheterization of the pulmonary artery was performed in the ICU and the cardiac output was measured by means of the Fick method. The pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) were determined. Epoprostenol was given in increasing doses to test reversibility of pulmonary hypertension. The maximum test dose was 12 ng kg(-1) min(-1). During each step simultaneous EIT (DAS-01 P Portable Data Acquisition System, Sheffield, England) measurements were performed with the 16 electrodes equidistantly positioned in the third intercostal space. The maximal systolic impedance change, relative to end-diastole, deltaZperf, was chosen as a measure of pulmonary perfusion. The impedance change between baseline and highest tolerable epoprostenol concentration was compared with the change in PVR. The mean PVR (dyn s/cm5) decreased from 636 (+/-399) to 366 (+/-242); p < 0.01. DeltaZperf (in arbitrary units) for the whole patient group increased from 901 (+/-295) x 10(-3) to 1082 (+/-472) x 10(-3) (p<0.05). Only one patient showed a reduction in pulmonary artery pressure >20%, which is defined as significant vasodilatation. A strong relationship was found between the impedance changes and the change in PVR and mPAP in the patient with a significant vasodilatation on epoprostenol. From these results we conclude that EIT is a reliable method to measure blood volume changes due to pharmacologically induced vasodilatation in the pulmonary bed. more...
- Published
- 2002
- Full Text
- View/download PDF
46. Determination of stroke volume by means of electrical impedance tomography.
- Author
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Vonk-Noordegraaf A 2nd, Janse A, Marcus JT, Bronzwaer JG, Postmust PE, Faes TJ, and De Vries PM
- Subjects
- Aged, Calibration, Cardiac Catheterization, Humans, Magnetic Resonance Imaging, Middle Aged, Point-of-Care Systems standards, Reproducibility of Results, Thermodilution, Tomography standards, Electric Impedance, Mitral Valve Stenosis diagnosis, Stroke Volume physiology, Tomography methods
- Abstract
ECG-gated electrical impedance tomography (EIT) is a non-invasive imaging technique, developed to monitor blood volume changes. This study is the first in comparing this non-invasive technique in measuring stroke volume with established techniques. The objective of this study was to validate EIT variables derived from the EIT images with paired obtained stroke volume measurements by thermodilution and MRI. After right cardiac catheterization, EIT measurements were performed in 25 patients. Regression analysis was used to analyse the relation between the EIT results and stroke volume determined by thermodilution. From the regression line an equation was derived to estimate stroke volume (in ml) by EIT. A strong correlation was found between EIT and stroke volume measured by the thermodilution method (r = 0.86). In a group of 11 healthy subjects this equation was validated to MRI. The mean and standard deviation of the difference between EIT and MRI was 0.7 ml and 5.4 ml respectively. These data indicate that EIT is a valid and reproducible method for the assessment of stroke volume. more...
- Published
- 2000
- Full Text
- View/download PDF
47. Magnetic resonance imaging of myocardial perfusion in single-vessel coronary artery disease: implications for transmural assessment of myocardial perfusion.
- Author
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Keijer JT, van Rossum AC, Wilke N, van Eenige MJ, Jerosch-Herold M, Bronzwaer JG, and Visser CA
- Subjects
- Adult, Aged, Animals, Blood Flow Velocity physiology, Contrast Media, Coronary Angiography, Coronary Circulation physiology, Dogs, Female, Gadolinium DTPA, Humans, Image Processing, Computer-Assisted, Least-Squares Analysis, Linear Models, Male, Microspheres, Middle Aged, Coronary Disease diagnosis, Coronary Disease physiopathology, Magnetic Resonance Imaging methods
- Abstract
The purpose of the study was to investigate the potential of magnetic resonance imaging (MRI) to assess transmural differences in myocardial perfusion. Contrast-enhanced MRI was performed at rest and during hyperemia in a dog model and in 22 patients with single-vessel coronary artery disease. From MR signal intensity-versus-time curves, three perfusion parameters were derived: maximum myocardial contrast enhancement (MCE), slope, and inverse mean transit time (1/MTT). In dogs, MCE correlated well (r = 0.87, p < 0.00001) with microsphere-assessed myocardial blood flow. In the patients, the subendocardial MCE decreased during hyperemia (0.89 +/- 0.18 vs. 0.74 +/- 0.15, p < 0.003) and was lower in subendocardium than in subepicardium (0.74 +/- 0.15 vs. 0.84 +/- 0.21, p < 0.02). Parameters slope and 1/MTT paralleled MCE. Contrast-enhanced MRI reflects the transmural redistribution of myocardial perfusion during hyperemia. Perfusion abnormalities can be identified most distinctly in subendocardial myocardium. more...
- Published
- 2000
- Full Text
- View/download PDF
48. Diastolic dysfunction in coronary artery disease.
- Author
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Bronzwaer JG
- Subjects
- Animals, Cardiac Pacing, Artificial, Diastole, Humans, Myocardial Ischemia physiopathology, Systole, Coronary Disease physiopathology, Ventricular Dysfunction, Left physiopathology
- Published
- 1999
49. Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy.
- Author
-
Heymes C, Vanderheyden M, Bronzwaer JG, Shah AM, and Paulus WJ
- Subjects
- Adult, Aged, Cardiac Catheterization, Cardiomyopathy, Dilated complications, Cardiomyopathy, Dilated enzymology, Coronary Angiography, Female, Heart Failure enzymology, Heart Failure etiology, Humans, Male, Middle Aged, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Regression Analysis, Reverse Transcriptase Polymerase Chain Reaction, Stroke Volume drug effects, Substance P pharmacology, Cardiomyopathy, Dilated physiopathology, Gene Expression Regulation, Enzymologic, Heart Failure physiopathology, Myocardium enzymology, Nitric Oxide Synthase genetics, Ventricular Function, Left drug effects
- Abstract
Background: Patients with heart failure have modified myocardial expression of nitric oxide synthase (NOS), as is evident from induction of calcium-insensitive NOS isoforms. The functional significance of this modified NOS gene expression for left ventricular (LV) contractile performance was investigated in patients with dilated nonischemic cardiomyopathy., Methods and Results: In patients with dilated, nonischemic cardiomyopathy, invasive measures of LV contractile performance were derived from LV microtip pressure recordings and angiograms and correlated with intensity of gene expression of inducible (NOS2) and constitutive (NOS3) NOS isoforms in simultaneously procured LV endomyocardial biopsies (n=20). LV endomyocardial expression of NOS2 was linearly correlated with LV stroke volume (P=0.001; r=0.66), LV ejection fraction (P=0.007; r=0.58), and LV stroke work (P=0.003; r=0.62). In patients with elevated LV end-diastolic pressure (>16 mm Hg), a closer correlation was observed between endomyocardial expression of NOS2 and LV stroke volume (P=0.001; r=0.74), LV ejection fraction (P=0.0007; r=0.77), and LV stroke work (r=0.82; P=0.0002). LV endomyocardial expression of NOS3 was linearly correlated with LV stroke volume (P=0.01; r=0.53) and LV stroke work (P=0.01; r=0.52). To establish the role of nitric oxide (NO) as a mediator of the observed correlations, substance P (which causes endothelial release of NO) was infused intracoronarily (n=12). In patients with elevated LV end-diastolic pressure, an intracoronary infusion of substance P increased LV stroke volume from 72+/-13 to 91+/-16 mL (P=0.06) and LV stroke work from 67+/-11 to 90+/-15 g. m (P=0.03) and shifted the LV end-diastolic pressure-volume relation to the right., Conclusions: In patients with dilated cardiomyopathy, an increase in endomyocardial NOS2 or NOS3 gene expression augments LV stroke volume and LV stroke work because of a NO-mediated rightward shift of the diastolic LV pressure-volume relation and a concomitant increase in LV preload reserve. more...
- Published
- 1999
- Full Text
- View/download PDF
50. The effect of renal transplantation on hyperhomocysteinaemia in dialysis patients, and the estimation of renal homocysteine extraction in patients with normal renal function.
- Author
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van Guldener C, Janssen MJ, Stehouwer CD, Jakobs C, Bronzwaer JG, Surachno J, and Donker AJ
- Subjects
- Adult, Aged, Chromatography, High Pressure Liquid, Female, Follow-Up Studies, Humans, Kidney metabolism, Kidney Failure, Chronic blood, Kidney Failure, Chronic therapy, Kidney Function Tests, Male, Middle Aged, Homocysteine blood, Kidney physiopathology, Kidney Failure, Chronic physiopathology, Kidney Transplantation physiology, Renal Dialysis
- Abstract
Background: The pathophysiology of hyperhomocysteinaemia in chronic renal failure (CRF) is unknown. Possible mechanisms are decreased renal homocysteine (Hcy) catabolism or inhibition of extrarenal Hcy metabolism by uraemic toxins., Methods: We studied the short-term effect on plasma Hcy concentration of improvement of renal function after successful kidney transplantation (n = 8), and determined renal Hcy extraction by measurement of total Hcy in arterial and renal venous blood in 7 cardiac patients with normal renal function., Results: Post-transplantation, plasma Hcy decreased with improving renal function. In the cardiac patients, no significant renal Hcy extraction could be demonstrated, but tubular disposal of the filtered load could not be excluded., Conclusions: Because loss of such renal metabolism could lead to hyperhomocysteinaemia in CRF, it is necessary to determine the renal extraction of free Hcy in subjects with normal renal function to further investigate renal homocysteine metabolism. more...
- Published
- 1998
- Full Text
- View/download PDF
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