Publications (61) View all
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Conference Proceeding: LV functional recovery from Tako-Tsubo cardiomyopathy is incomplete after 3 months: evidence from 2D speckle-tracking echocardiography.
European Society Cardiology; 03/2012 -
Article: Potential mechanisms of the acute coronary syndrome presentation in patients with the coronary slow flow phenomenon - insight from a plasma proteomic approach.
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ABSTRACT: The coronary slow flow phenomenon [CSFP] is a coronary microvascular disorder, characterized by delayed distal vessel opacification despite the absence of obstructive coronary artery disease. Patients frequently present with an acute coronary syndrome [ACS] although the pathophysiological mechanisms responsible are unknown. The aim of this study was to identify potential mechanisms for the ACS presentation associated with the CSFP using a plasma proteomic profiling approach. Plasma samples from nine CSFP subjects [56 ± 11years] were assayed for high sensitivity C-reactive protein [hsCRP], troponin T [TnT], creatine kinase [CK], and proteomic analyses (n=6), during an ACS presentation and one month later [chronic phase]. Proteomic analysis involved chromatographic depletion of abundant plasma proteins followed by two-dimensional differential gel electrophoresis [2-D DIGE]. Protein spots demonstrating ±1.5-fold change relative to the control were identified by mass spectrometry and two differentially expressed proteins were selected for validation via Western blotting. During the ACS presentation, hsCRP was elevated [ACS=14.9 ± 3.9 mg/L vs chronic=4.23 ± 1.37 mg/L, p=0.05] but TnT and CK levels were unchanged. Proteomic analysis identified six proteins that were significantly different in abundance between the acute and chronic samples. During the ACS presentation there was a 1.6 ± 0.13 fold increase in the anti-oxidant enzyme paraoxonase-1 and an increase in inflammatory proteins alpha-1-antichymotrypsin [1.65 ± 0.13 fold] and alpha-1-antitrypsin [2.5 ± 0.34 fold]. The latter was confirmed by Western blotting [1.33 ± 0.17 OD acute/chronic ratio, p=0.05]. The findings from this novel detailed approach, implicate an inflammatory/oxidative stress process in the pathogenesis of the ACS presentation associated with the CSFP. Future studies should further elucidate these mechanisms.International journal of cardiology 09/2011; 156(1):84-91. · 7.08 Impact Factor -
Article: Coronary β2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study.
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ABSTRACT: AIMS: The interaction between coronary β(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary β(2)-adrenoreceptors, regional plaque burden and segmental endothelial function. METHODS AND RESULTS: In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 μg/min) infusions (15 patients, 103 segments); protocol 2: salbutamol (0.30 μg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 μg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS; 0.30 μg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001; 0.60 μg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and microvascular coronary vasodilator. Intravascular ultrasound-derived regional plaque burden is a major determinant of segmental coronary endothelial function.European Heart Journal 09/2011; 33(4):495-504. · 10.48 Impact Factor -
Article: N-terminal pro-brain natriuretic protein levels in takotsubo cardiomyopathy.
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ABSTRACT: Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular (LV) systolic dysfunction independent of fixed coronary disease or coronary spastic pathogenesis. A number of investigators have documented marked elevation of natriuretic peptide levels at presentation in such patients. We sought to determine the pattern, extent, and determinants of the release of N-terminal pro-B type natriuretic peptide/B type natriuretic peptide (NT-proBNP/BNP) in patients with TTC. We evaluated NT-proBNP/BNP release acutely and during the first 3 months in 56 patients with TTC (96% women, mean age 69 ± 11 years). The peak plasma NT-proBNP levels were compared to the pulmonary capillary wedge pressure and measures of regional and global LV systolic dysfunction (systolic wall stress, wall motion score index, and LV ejection fraction) as potential determinants of NT-proBNP/BNP release. In patients with TTC, the plasma concentrations of NT-proBNP (median 4,382 pg/ml, interquartile range 2,440 to 9,019) and BNP (median 617 pg/ml, interquartile range 426 to 1,026) were substantially elevated and increased significantly during the first 24 hours after the onset of symptoms (p = 0.001), with slow and incomplete resolution during the 3 months thereafter. The peak NT-proBNP levels exhibited no significant correlation with either pulmonary capillary wedge pressure or systolic wall stress. However, the peak NT-proBNP level correlated significantly with the simultaneous plasma normetanephrine concentrations (r = 0.53, p = 0.001) and the extent of impairment of LV systolic function, as measured by the wall motion score index (r = 0.37, p = 0.008) and LV ejection fraction (r = -0.39, p = 0.008). In conclusion, TTC is associated with marked and persistent elevation of NT-proBNP/BNP levels, which correlated with both the extent of catecholamine increase and the severity of LV systolic dysfunction.The American journal of cardiology 08/2011; 108(9):1316-21. · 3.58 Impact Factor -
Article: Quality of life of patients with peripheral arterial disease and chronic stable angina.
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ABSTRACT: The Coronary Artery Disease in gENeral practiCE (CADENCE) study examined chronic stable angina (CSA). This further analysis examined atherosclerotic risk factors, symptomatic status, clinical management, and quality of life in patients with CSA with and without peripheral arterial disease (PAD). The CADENCE study involved 207 Australian general practitioners (GPs) recruiting 10 to 15 consecutively presenting patients with CSA (n = 2031). General practitioners completed a 2-page case report form, detailing demographic data, cardiovascular status, risk factors, and GP perception of control. Patients completed the Seattle Angina Questionnaire. Patients with coexisting CSA and PAD (17%) were more likely to be older and had more comorbidities than patients with CSA without coexisting PAD. Patients with peripheral arterial disease had a longer history of heart disease and were more likely to experience angina on a weekly basis. Patients with peripheral arterial disease had poorer quality-of-life indices.Angiology 07/2011; 63(3):223-8. · 1.51 Impact Factor
