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Giuseppe Tarantini,
Enrico Favaretto,
Martina Perazzolo Marra,
Anna Chiara Frigo,
Massimo Napodano,
Luisa Cacciavillani,
Andrea Giovagnoni,
Pietro Renda,
Valeria De Biasio,
Mario Plebani, Monica Mion,
Martina Zaninotto,
Giambattista Isabella,
Claudio Bilato,
Sabino Iliceto
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ABSTRACT: BACKGROUND: Postconditioning (PC) has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI), nevertheless clinical experience is limited. We aimed to explore the cardioprotective effect of PC using cardiac magnetic resonance (CMR) in ST-elevation myocardial infarction (STEMI) patients treated by PPCI. METHODS: A total of 78 patients with first STEMI (aged 59±12years) referred for PPCI, were stratified for STEMI location and randomly assigned to conventional PPCI or PPCI with PC. All patients, with occluded infarct related artery and no collateral circulation, received abciximab intravenously before PPCI. After reperfusion by effective direct stenting, control subjects underwent no further intervention, while in treated patients PC was performed within 1min of reflow by 4 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Primary end-point was infarct size (IS) reduction, expressed as percentage of left ventricle mass assessed by delayed enhancement on CMR at 30±10days after index PPCI. RESULTS: All baseline characteristics but diabetes (p=0.06) were balanced between groups. Postconditioning patients trended toward a larger IS compared to those treated by standard PPCI (20±12% vs 14±10%, p=0.054). After exclusion of diabetics, PC group still showed a trend to larger IS (p=0.116). Major adverse events seem to be more frequent in PC group irrespective to diabetic status (p=0.053 and p=0.080, respectively). CONCLUSIONS: This prospective, randomized trial suggests that PC did not have the expected cardioprotective effect and on the contrary it might harm STEMI patients treated by PPCI plus abciximab. (Clinical Trial Registration-unique identifier: NCT01004289).
International journal of cardiology 04/2012; · 7.08 Impact Factor
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Gian Paolo Fadini,
Mattia Albiero,
Lisa Menegazzo,
Elisa Boscaro,
Saula Vigili de Kreutzenberg,
Carlo Agostini,
Anna Cabrelle,
Gianni Binotto,
Marcello Rattazzi,
Elisa Bertacco, [......],
Giulio Ceolotto,
Annalisa Angelini,
Chiara Castellani,
Mirko Menegolo,
Franco Grego,
Stefanie Dimmeler,
Florian Seeger,
Andreas Zeiher,
Antonio Tiengo,
Angelo Avogaro
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ABSTRACT: Acquisition of a procalcific phenotype by resident or circulating cells is important for calcification of atherosclerotic plaques, which is common in diabetes.
We aim to identify and characterize circulating calcifying cells, and to delineate a pathophysiological role for these cells in type 2 diabetes.
We demonstrate for the first time that a distinct subpopulation of circulating cells expressing osteocalcin and bone alkaline phosphatase (OC(+)BAP(+)) has procalcific activity in vitro and in vivo. The study of naïve patients with chronic myeloid leukemia indicated that OC(+)BAP(+) cells have a myeloid origin. Myeloid calcifying OC(+)BAP(+) cells (MCCs) could be differentiated from peripheral blood mononuclear cells, and generation of MCCs was closely associated with expression of the osteogenic transcription factor Runx2. In gender-mismatched bone marrow-transplanted humans, circulating MCCs had a much longer half-life compared with OC(-)BAP(-) cells, suggesting they belong to a stable cell repertoire. The percentage of MCCs was higher in peripheral blood and bone marrow of type 2 diabetic patients compared with controls but was lowered toward normal levels by optimization of glycemic control. Furthermore, diabetic carotid endoarterectomy specimens showed higher degree of calcification and amounts of cells expressing OC and BAP in the α-smooth muscle actin-negative areas surrounding calcified nodules, where CD68(+) macrophages colocalize. High glucose increased calcification by MCCs in vitro, and hypoxia may regulate MCC generation in vitro and in vivo.
These data identify a novel type of blood-derived procalcific cells potentially involved in atherosclerotic calcification of diabetic patients.
Circulation Research 03/2011; 108(9):1112-21. · 9.49 Impact Factor
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Clinical Chemistry and Laboratory Medicine 11/2010; 48(11):1677-9. · 2.15 Impact Factor
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Giuseppe Tarantini,
Enrico Favaretto,
Massimo Napodano,
Martina Perazzolo Marra,
Luisa Cacciavillani,
Luciano Babuin,
Andrea Giovagnoni,
Pietro Renda,
Valeria De Biasio,
Mario Plebani, Monica Mion,
Martina Zaninotto,
Flavio Mistrorigo,
Marco Panfili,
Giambattista Isabella,
Claudio Bilato,
Sabino Iliceto
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ABSTRACT: Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events.
The POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) trial is a single-center, prospective, randomized study, with a planned inclusion of 78 patients with ST-elevation AMI. Patients will be randomly assigned to the postconditioning arm [primary angioplasty (PA) and stenting followed by brief episodes of ischemia-reperfusion early after recanalization] or non-postconditioning arm. All patients will be treated medically according to current international guidelines, including glycoprotein IIb/IIIa inhibitors before PA. The primary end point is to evaluate whether postconditioning, compared to plain PA, reduces infarct size estimated by cardiac magnetic resonance (CMR) at 30 +/- 10 days after the AMI. Secondary end points are microvascular obstruction observed at CMR, ST-segment resolution, angiographic myocardial blush grade <2, non-sustained/sustained ventricular tachycardia in the 48 h following PA, left ventricular remodeling and function at follow-up CMR, and the reduction of major adverse cardiac events at 30 days and 6 months.
The POST-AMI trial will evaluate the usefulness of postconditioning in limiting infarct size during the early and late phases after AMI.
Cardiology 07/2010; 116(2):110-6. · 1.71 Impact Factor
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ABSTRACT: The reliability of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) as biochemical markers of heart failure in comparison to B-type natriuretic peptide (BNP) has not been investigated in depth.
To compare the correlations between IL-6, TNF, BNP plasma concentrations and some clinical and instrumental variables and their prognostic value in heart failure patients.
In 79 patients with heart failure, the correlations between IL-6, TNF and BNP plasma concentrations and a series of 18 variables were studied. Outcome events were death from any cause and combined death and heart transplantation.
At univariate analysis, BNP and IL-6 plasma concentrations correlated with each other (r = 0.4828; P < 0.0001), with New York Heart Association class, fluid retention, left ventricular ejection fraction, mean right atrial pressure, mean pulmonary pressure and cardiac index. All these correlations were stronger with BNP. TNF plasma concentration correlated only with New York Heart Association class and left ventricular ejection fraction.During follow-up, 1-32 months, 14 patients died and nine underwent heart transplantation. At univariate analysis, both BNP and IL-6 plasma concentrations were predictors of death and heart transplantation, but only BNP was a predictor of death; however, only creatinine plasma level was an independent predictor of prognosis.
IL-6 and TNF are less reliable biochemical markers than BNP in heart failure patients.
Journal of Cardiovascular Medicine 06/2009; 10(10):758-64. · 1.51 Impact Factor
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ABSTRACT: The diagnostic value of natriuretic peptides in uremic cardiomyopathy has not been defined, nor has the effect of a hemodialysis (HD) session on peptides.
We performed an observational study of 100 white adult outpatients in New York Heart Association class I-II, with neither diabetes nor ischemic heart disease, 50 of whom had idiopathic dilated cardiomyopathy (DCM) and 50 of whom had uremic cardiomyopathy and were undergoing HD. We measured plasma N-terminal proB-type natriuretic peptide (NT-proBNP), BNP, and atrial natriuretic peptide (ANP) both before and after a dialysis session. Doppler echocardiograms were evaluated. We performed multiple regression analysis on the logarithm of peptide concentrations using clinical, laboratory, and echocardio-Doppler data as explanatory variables.
Mean peptide concentrations were higher in the HD group, with an HD:DCM ratio of 25 for NT-proBNP and 5 for BNP and ANP. Peptides were correlated with each other (r > 0.85). After HD, NT-proBNP significantly increased by 14%, BNP decreased by 17%, and ANP decreased by 56%. Predialysis concentrations correlated with postdialysis values (r > 0.85). A multiple regression equation significantly fitted the observed peptide concentrations, both pre- and postdialysis, using the same set of 4 variables: disease group (DCM or HD), diastolic pattern, left atrial volume, and body mass index.
Renal dysfunction was a confounder for natriuretic peptides, which were present in higher concentrations in the uremic patients with milder cardiac dysfunction than in those with idiopathic DCM without renal dysfunction. Left diastolic function pattern and atrial volume were cardiac determinants of peptide concentrations in DCM and HD.
Clinical Chemistry 12/2007; 53(12):2097-104. · 7.91 Impact Factor
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ABSTRACT: Plasma apelin concentration in heart failure has been described in small studies reporting conflicting results. In hemodialysis (HD) patients, apelin decreased more in those with more severe heart involvement. It is unclear if uremia is connected to this reduction irrespective of heart failure. We compared apelin in two cardiomyopathies with different renal function.
Observational study conducted in 30 adult Caucasian outpatients in class I NYHA not affected by diabetes or ischemic heart, 15 with idiopathic dilated cardiomyopathy (DCM) and 15 with uremic dilated cardiomyopathy undergoing HD. Plasma apelin, creatinine, high-sensitivity C-reactive protein, endothelin, NT proB-type natriuretic peptide (NT-proBNP), and Doppler echocardiogram were evaluated.
Heart involvement was more severe in the DCM patients (lower ejection fraction, greater diastolic volume index, and worse index of myocardial performance). Median value of apelin in HD patients (19.1 pg/ml) was one third of that in DCM patients (58.2 pg/ml) whereas creatinine, NT-proBNP, and C-reactive protein were 11, 80, and 9 times higher respectively in HD than in DCM patients. Median values of endothelin were comparable in both groups. Apelin was not significantly correlated with any variable.
Uremic status was the determinant for decreased plasma apelin in HD patients regardless of the severity of heart involvement.
American Journal of Nephrology 02/2007; 27(1):1-6. · 2.54 Impact Factor
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ABSTRACT: The purpose of this study was to verify the usefulness of NT-proBNP in the differential diagnosis of dyspnea in a population of patients presenting in the ER with breathlessness.
In samples from 122 patients presenting in the ER with acute-severe dyspnea and from 25 subjects enrolled as a "comparison group" (NORM), NT-proBNP levels were measured. Patients have been classified on the basis of discharge diagnosis: pulmonary disease (PD, n = 23), pulmonary concomitant to cardiac disease (MIXED, n = 17), pulmonary embolism (EMB, n = 8), cardiac disease (CARD, n = 56), acute myocardial infarction (AMI, n = 11) and other disease (OTHER, n = 7).
A significant difference in NT-proBNP values (P <or= 0.05) was found in CARD vs. PD as well as vs. NORM and OTHER groups. 1760 ng/L was the best cut-off value calculated from ROC analysis (AUC +/- SE 0.815 +/- 0.041). Comparing NT-proBNP values and ER diagnosis, a disagreement in 24 patients was observed. Using the discharge diagnosis as the "gold standard," four cases (17%) were found to be FP and 11 cases (46%) were FN according to ER diagnosis, while 2 patients showed false positive and 7 false negative NT-proBNP values.
NT-proBNP measurement represents a useful biochemical tool helping the ER physician in the rapid and reliable recognition of cardiac involvement in patients presenting in the ER with acute-severe dyspnea.
Clinical Biochemistry 12/2005; 38(11):1041-4. · 2.08 Impact Factor
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Clinical Chemistry 02/2002; 48(4):677-9. · 7.91 Impact Factor
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ABSTRACT: Cystatin is an ubiquitous protease inhibitor involved in degradation of cellular proteins and has recently been associated with increased risk of cardiovascular disease and heart failure independent of renal function. We tested whether cystatin in heart failure is only associated with renal function or also with echocardio-Doppler parameters and factors of myocardial remodeling (C-reactive protein, endothelin, and natriuretic peptides).
This was an observational study conducted in 100 adult Caucasian outpatients with NYHA class I-II heart function without diabetes and ischemic heart, 50 with idiopathic dilated cardiomyopathy (DCM) and 50 with uremic cardiomyopathy undergoing hemodialysis (HD). Multiple linear regression analysis was performed on cystatin concentration using clinical, laboratory (creatinine, high sensitivity C-reactive protein, endothelin, B-type natriuretic peptide [BNP]) and echocardio-Doppler data as explanatory variables.
The heart was more severely involved in DCM patients (worse ejection fraction, diastolic volume index, index of myocardial performance, left ventricular mass index). Mean values of cystatin, creatinine, BNP and C-reactive protein in HD compared with DCM patients were 6, 9, 5 and 3 times higher, respectively. Mean values of endothelin were comparable in both groups. Cystatin significantly correlated with creatinine in both groups (r=0.50 in DCM and r=0.37 in HD, and r=0.95 in pooled groups). In the multiple regression analysis, only disease group and creatinine within groups were significant independent factors that accounted for 94% of the variability of cystatin.
Renal function was the determinant of cystatin in a concentration range of 6 times regardless of severity of heart involvement.
Journal of nephrology 20(2):219-27. · 1.65 Impact Factor