Pubblicazioni - De Chiara Dott.ssa Benedetta

• Sequencing of NOTCH1 gene in an Italian population with bicuspid aortic valve: Preliminary results from the GISSI OUTLIERS VAR study.
  Gene

  2019 Oct;715():143970. doi: S0378-1119(19)30620-1.
  
  Pileggi Silvana, De Chiara Benedetta, Magnoli Michela, Franzosi Maria Grazia, Merlanti Bruno, Bianchini Francesca, Moreo Antonella, Romeo Gabriella, Russo Claudio Francesco, Rizzo Stefania, Basso Cristina, Martinelli Luigi, Maseri Attilio,
  
  Abstract
  
  BACKGROUND:
  Bicuspid aortic valve (BAV) formation is genetically determined, with reduced penetrance and variable expressivity. NOTCH1 is a proven candidate gene and its mutations have been found in familial and sporadic cases of BAV.
  
  METHODS:
  66 BAV patients from the GISSI VAR study were genotyped for the NOTCH1 gene.
  
  RESULTS:
  We identified 63 variants, in heterozygous and homozygous states. Fifty-two are common polymorphisms present in almost all patients. Eleven variants are new and never yet reported: two are non-synonymous substitutions, Gly540Asp in exon 10 and Glu851Gln in exon 16; one is in the 3'UTR region and seven in introns, one corresponds to a T allele insertion in intron 27. We selected four statistically noteworthy and seven new variants identified in six BAV patients and correlated them with clinical and demographic variables and with imaging and histological parameters. Preliminary data show that four were BAV patients with isolated stenosis in patients over 60 aged. These variants may correlate with a later need for surgery for the presence of stenosis and not aortic valve regurgitation or ascending aortic aneurysm.
  
  CONCLUSIONS:
  Completing the genotyping of 62 BAV patients we found 11 new variants in the NOTCH1 gene never yet reported. These findings confirm that the identification of new, clinically remarkable biomarkers for BAV requires a deeper genetic understanding of the NOTCH1 gene variants, which could be targeted by future diagnostic and therapeutic strategies.
  
  Copyright © 2019 Elsevier B.V. All rights reserved.
  
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• Could two-dimensional radial strain be considered as a novel tool to identify pre-clinical hypertrophic cardiomyopathy mutation carriers?
  Int J Cardiovasc Imaging

  2019 Dec;35(12):2167-2175. doi: 10.1007/s10554-019-01668-9.
  
  Santambrogio Gloria Maria, Maloberti Alessandro, Vallerio Paola, Peritore Angelica, Spanò Francesca, Occhi Lucia, Musca Francesco, Belli Oriana, De Chiara Benedetta, Casadei Francesca, Facchetti Rita, Turazza Fabio, Manfredini Emanuela, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph-); Group C (9 patients), healthy subjects (G-/Ph-). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18%?±?9.6 vs. 44.59%?±?12.67 respectively; p-value?
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• Pulse wave velocity progression over a medium-term follow-up in hypertensives: Focus on uric acid.
  J Clin Hypertens (Greenwich)

  2019 Jul;21(7):975-983. doi: 10.1111/jch.13603.
  
  Maloberti Alessandro, Rebora Paola, Andreano Anita, Vallerio Paola, De Chiara Benedetta, Signorini Stefano, Casati Marco, Besana Silvia, Bombelli Michele, Grassi Guido, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow-up period in hypertensive patients. Specific sex analysis was done due to the well-known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow-up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow-up, despite better BP values (-8.5 ± 24.6 for SBP and -7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P < 0.001) with mean ?PWV of+ 0.5 ± 2.2 m/s. A total of 61 patients were hyperuricemic (14.4%), and they present higher PWV baseline (9.0 ± 2.5 vs 8.5 ± 1.8 m/s, P = 0.03) without significant differences in ?PWV. Hyperuricemic female (6.2%, 11 patients) presents higher baseline PWV without significant differences in ?PWV. No differences were found in arterial stiffness in hyperuricemic males (20.4%, 50 patients). UA showed association with baseline and ?PWV in the whole population but it loses statistical significance at the linear regression model. Same figures were also for sex analysis. Our findings provide evidence that baseline UA levels are not determinants of PWV progression over a median follow-up of 3.8 years' in hypertensive patients.
  
  ©2019 Wiley Periodicals, Inc.
  
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• Impact of serial echocardiography in the management of primary cardiac lymphoma.
  J Saudi Heart Assoc

  2018 Apr;30(2):160-163. doi: 10.1016/j.jsha.2017.08.001.
  
  Cereda Alberto Francesco, Moreo Antonella Maurizia, Sormani Paola, De Chiara Benedetta, Casadei Francesca, Zancanella Michelle, Rusconi Chiara, Cairoli Roberto, Giannattasio Cristina
  
  
  
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• Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.
  Nutrition

  2017 Jun;38():41-47. doi: S0899-9007(17)30001-1.
  
  Campolo Jonica, Bernardi Stefano, Cozzi Lorena, Rocchiccioli Silvia, Dellanoce Cinzia, Cecchettini Antonella, Tonini Annamaria, Parolini Marina, De Chiara Benedetta, Micheloni Gianpaolo, Pelosi Gualtiero, Passino Claudio, Giannattasio Cristina, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF).
  
  METHODS:
  We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000.
  
  RESULTS:
  In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (?1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively).
  
  CONCLUSIONS:
  Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.
  
  Copyright © 2017 Elsevier Inc. All rights reserved.
  
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• Infective endocarditis of an aortic intimal flap due to Streptococcus agalactiae in a patient with Sjögren's syndrome: an unusual clinical case report.
  Echocardiography

  2016 Sep;33(9):1434-5. doi: 10.1111/echo.13274.
  
  De Chiara Benedetta, Peritore Angelica, Sara Roberto, Giannattasio Cristina, Moreo Antonella
  
  
  
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• [Highlights from the 2015 ESC guidelines for the management of infective endocarditis].
  G Ital Cardiol (Rome)

  2016 Apr;17(4):245-7. doi: 10.1714/2214.23892.
  
  De Chiara Benedetta, Gerometta Piersilvio
  
  
  
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• Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel.
  Interact Cardiovasc Thorac Surg

  2016 Mar;22(3):371-3. doi: 10.1093/icvts/ivv349.
  
  Maloberti Alessandro, Oliva Fabrizio, De Chiara Benedetta, Giannattasio Cristina
  
  Abstract
  
  Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40-year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 × 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, ?-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control.
  
  © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• [The conundrum of therapeutic management in acute myocardial infarction complicated by endoventricular thrombosis: moving between different risks].
  G Ital Cardiol (Rome)

  ;16(7-8):437-41. doi: 10.1714/1954.21248.
  
  Varrenti Marisa, Morici Nuccia, De Chiara Benedetta, Oreglia Jacopo Andrea, Pedrotti Patrizia, Giannattasio Cristina, Klugmann Silvio, Roghi Alberto
  
  Abstract
  
  Coronary artery disease is a rare entity in young patients and accurate assessment of its prevalence is difficult. Although coronary artery disease is frequently a silent process, it may also acutely present with myocardial infarction (MI). One of the most feared complications of MI is left ventricular thrombus formation. Transthoracic echocardiography is recommended for all patients with MI, and cardiac magnetic resonance should be considered because of its higher sensitivity if thrombus cannot clearly be demonstrated. The optimal treatment is based on anticoagulant therapy that should be started early and maintained for 3-4 months after the index event. We report the case of a 35-year-old male patient with anterior MI, complicated by left ventricular thrombus formation, extensive edema, microvascular obstruction and hemorrhagic core of the apical septum on cardiac magnetic resonance assessment.
  
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• Clinical impact and evolution of mitral regurgitation following transcatheter aortic valve replacement: a meta-analysis.
  Heart

  2015 Sep;101(17):1395-405. doi: 10.1136/heartjnl-2014-307120.
  
  Nombela-Franco Luis, Eltchaninoff Hélène, Zahn Ralf, Testa Luca, Leon Martin B, Trillo-Nouche Ramiro, D'Onofrio Augusto, D Onofrio Augusto, Smith Craig R, Webb John, Bleiziffer Sabine, De Chiara Benedetta, Gilard Martine, Tamburino Corrado, Bedogni Francesco, Barbanti Marco, Salizzoni Stefano, García del Blanco Bruno, Sabaté Manel, Moreo Antonella, Fernández Cristina, Ribeiro Henrique Barbosa, Amat-Santos Ignacio, Urena Marina, Allende Ricardo, García Eulogio, Macaya Carlos, Dumont Eric, Pibarot Philippe, Rodés-Cabau Josep
  
  Abstract
  
  OBJECTIVES:
  Mitral regurgitation (MR) is a common entity in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but its influence on outcomes remains controversial. The purpose of this meta-analysis was to assess the clinical impact of and changes in significant (moderate-severe) MR in patients undergoing TAVR, overall and according to valve design (self-expandable (SEV) vs balloon-expandable (BEV)).
  
  METHODS:
  All national registries and randomised trials were pooled using meta-analytical guidelines to establish the impact of moderate-severe MR on mortality after TAVR. Studies reporting changes in MR after TAVR on an individual level were electronically searched and used for the analysis.
  
  RESULTS:
  Eight studies including 8015 patients (SEV: 3474 patients; BEV: 4492 patients) were included in the analysis. The overall 30-day and 1-year mortality was increased in patients with significant MR (OR 1.49, 95% CI 1.16 to 1.92; HR 1.32, 95% CI 1.12 to 1.55, respectively), but a significant heterogeneity across studies was observed (p<0.05). The impact of MR on mortality was not different between SEV and BEV in meta-regression analysis for 30-day (p=0.360) and 1-year (p=0.388) mortality. Changes in MR over time were evaluated in nine studies including 1278 patients. Moderate-severe MR (SEV: 326 patients; BEV: 192 patients) improved in 50.5% of the patients at a median follow-up of 180 (30-360) days after TAVR, and the degree of improvement was greater in patients who had received a BEV (66.7% vs 40.8% in the SEV group, p=0.001).
  
  CONCLUSIONS:
  Concomitant moderate-severe MR was associated with increased early and late mortality following TAVR. A significant improvement in MR severity was detected in half of the patients following TAVR, and the degree of improvement was greater in those patients who had received a BEV.
  
  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
  
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• Echocardiographic Assessment and Successful Valvular Repair of Congenital Mitral Arcade.
  J Cardiovasc Echogr

  ;25(2):57-59. doi: 10.4103/2211-4122.161781.
  
  Sormani Paola, Chiara Benedetta De, Taglieri Corrado, Moreo Antonella
  
  Abstract
  
  Anomalous mitral arcade is a rare congenital anomaly affecting the mitral tensor apparatus. This condition causes a restrictive movement of the leaflets and interferes with the normal closure of the valve during ventricular systole. We report a case of a 15-year-old female with this condition and initial left ventricular dysfunction, who successfully underwent mitral valve repair. This reparative technique is more technically challenging then valve replacement and only few cases are described in literature.
  
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• Left ventricular or Bi-ventricular assist device? How dobutamine stress echocardiography can untie the dilemma of right ventricular dysfunction.
  Int J Cardiol

  2014 Nov;177(1):e6-8. doi: 10.1016/j.ijcard.2014.07.194.
  
  Ammirati Enrico, Cipriani Manlio, De Chiara Benedetta, D'Angelo Luciana, Belli Oriana, Moreo Antonella, Oliva Fabrizio, Martinelli Luigi, Frigerio Maria
  
  
  
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• Transcatheter aortic valve implantation after heart transplantation.
  Ann Thorac Surg

  2010 Nov;90(5):e66-8. doi: 10.1016/j.athoracsur.2010.08.021.
  
  Bruschi Giuseppe, De Marco Federico, Oreglia Jacopo, Colombo Paola, Moreo Antonella, De Chiara Benedetta, Paino Roberto, Frigerio Maria, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  Conventional cardiac surgical procedures after orthotopic heart transplantation are generally uncommon. We report the case of a 67-year-old man who had severe symptomatic aortic stenosis develop 9 years after heart transplantation. After joint evaluation of the cardiovascular team, transcatheter aortic valve implantation was preferred due to patient medical conditions. The CoreValve prosthesis (Medtronic, Minneapolis, MN) was inserted percutaneously into the femoral artery. At 4 months postoperatively, the patient is asymptomatic in New York Heart Association functional class II. This case report provides evidence that transcatheter aortic valve implantation is safe and suitable for selected patients with severe aortic stenosis and a history of heart transplantation that must improve allograft function.
  
  Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• The trans-subclavian retrograde approach for transcatheter aortic valve replacement: single-center experience.
  J Thorac Cardiovasc Surg

  2010 Oct;140(4):911-5, 915.e1-2. doi: 10.1016/j.jtcvs.2010.01.027.
  
  Bruschi Giuseppe, Fratto Pasquale, De Marco Federico, Oreglia Jacopo, Colombo Paola, Botta Luca, Cannata Aldo, Moreo Antonella, De Chiara Benedetta, Lullo Francesca, Paino Roberto, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  OBJECTIVE:
  Aortic valve disease is the most common acquired valvular heart disease in adults. With the increasing elderly population, the proportion of patients with symptomatic aortic stenosis who are unsuitable for conventional surgery is increasing. Transcatheter aortic valve implantation has rapidly gained credibility as a valuable alternative to surgery to treat these patients; however, they often have severe iliac-femoral arteriopathy, which renders the transfemoral approach unusable. We report our experience with the trans-subclavian approach for transcatheter aortic valve implantation using the CoreValve (Medtronic CV Luxembourg S.a.r.l.) in 6 patients.
  
  METHODS:
  In May 2008 to September 2009, 6 patients (mean age of 82 ± 5 years), with symptomatic aortic stenosis and no reasonable surgical option because of excessive risk, were excluded from percutaneous femoral CoreValve implantation because of iliac-femoral arteriopathy. These patients underwent transcatheter aortic valve implantation via the axillary artery. Procedures were performed by a combined team of cardiologists, cardiac surgeons, and anesthetists in the catheterization laboratory. The CoreValve 18F delivery system was introduced via the left subclavian artery in 6 patients, 1 with a patent left internal thoracic to left anterior descending artery graft.
  
  RESULTS:
  Procedural success was obtained in all patients, and the mean aortic gradient decreased 5 mm Hg or less immediately after valve deployment. One patient required implantation of a permanent pacemaker. One patient required a subclavian covered stent implantation to treat a postimplant artery dissection associated with difficult surgical hemostasis. One patient was discharged in good condition but died of pneumonia 40 days after the procedure. All patients were asymptomatic on discharge, with good mid-term prosthesis performance.
  
  CONCLUSIONS:
  Transcatheter aortic valve implantation via a surgical subclavian approach seems safe and feasible, offering a new option to treat select, inoperable, and high-risk patients with severe aortic stenosis and peripheral vasculopathy.
  
  Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
  
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• Plasma cysteine and glutathione are independent markers of postmethionine load endothelial dysfunction.
  Clin Biochem

  2007 Feb;40(3-4):188-93.
  
  Parodi Oberdan, De Chiara Benedetta, Baldassarre Damiano, Parolini Marina, Caruso Raffaele, Pustina Linda, Parodi Guido, Campolo Jonica, Sedda Valentina, Baudo Francesco, Sirtori Cesare
  
  Abstract
  
  OBJECTIVES:
  Oxidative stress caused by acute hyperhomocysteinemia impairs endothelial function in human arteries. We sought to identify markers of endothelial dysfunction during methionine-induced hyperhomocysteinemia.
  
  DESIGN AND METHODS:
  35 subjects underwent flow-mediated dilation (FMD) of the brachial artery by high-resolution ultrasonography and fasting blood samples before and 3 h postmethionine load (PML). Clinical, conventional biochemical, and redox status (plasma total and reduced homocysteine, glutathione, cysteine, cysteinylglycine, ascorbic acid, alpha-tocopherol, free malondialdehyde, blood glutathione) data were sequentially entered into an univariate and multivariate stepwise linear regression analysis to evaluate their relation with the dependent variable FMD.
  
  RESULTS:
  Median [interquartile range] FMD decreased from 4.1% [2.8-6.3] to 3.2% [0.7-4.3] PML (P=0.02). At the multivariate analysis PML total cysteine (beta=-0.008, P=0.002) and glutathione (beta=0.21, P=0.005) were the only independent variables associated with FMD after methionine, adjusted for baseline FMD.
  
  CONCLUSIONS:
  Elevated plasma total cysteine and decreased plasma total glutathione levels were associated with abnormal FMD PML. Cysteine and glutathione are stronger markers of endothelial dysfunction than clinical and all other biochemical variables explored.
  
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• Effect of homocysteine lowering by 5-methyltetrahydrofolate on redox status in hyperhomocysteinemia.
  J Cardiovasc Pharmacol

  2006 Apr;47(4):549-55.
  
  Caruso Raffaele, Campolo Jonica, Sedda Valentina, De Chiara Benedetta, Dellanoce Cinzia, Baudo Francesco, Tonini Annamaria, Parolini Marina, Cighetti Giuliana, Parodi Oberdan
  
  Abstract
  
  The endothelial dysfunction induced by hyperhomocysteinemia can be reversed by 5-methyltetrahydrofolate (5-MTHF) via homocysteine (Hcy) lowering. An additive antioxidant action of 5-MTHF has been suggested to ameliorate endothelial dysfunction through increased nitric oxide production and superoxide radical scavenging, independent of Hcy lowering. The aim of the study was to assess whether 5-MTHF affects the redox state in hyperhomocysteinemia. We examined the effect of 3 months of oral 5-MTHF treatment (15 mg/day) on the redox pattern in 48 hyperhomocysteinemic subjects compared to 24 untreated hyperhomocysteinemic subjects. By analysis of variance with repeated measures in the 72 subjects, 5-MTHF markedly decreased plasma total Hcy (p-tHcy; P = 0.0001) and blood-total glutathione (GSH; b-tGSH; P = 0.002). By multivariate linear regression in the treated subjects, p-tHcy changes from baseline to 3 months (adjusted by baseline p-tHcy levels) correlated only with changes in reduced cysteinylglycine (P = 0.001). The effects of treatment on Hcy lowering and GSH metabolism were greater in medium than in moderate hyperhomocysteinemia. In conclusion, high-dose 5-MTHF treatment for 3 months ensures marked Hcy lowering to normal values even in subjects with high Hcy levels, and should be the treatment of choice in medium hyperhomocysteinemia. Furthermore, 5-MTHF shows a favorable interaction with GSH metabolism.
  
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• Usefulness of chronotropic incompetence to dipyridamole in predicting myocardial perfusion defects in heart transplant recipients.
  Am J Cardiol

  2003 Oct;92(8):1001-4.
  
  De Chiara Benedetta, Bigi Riccardo, Devoto Emmanuela, Cavenaghi Giorgio, Turazza Fabio, Sara Roberto, Colombo Tiziano, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects.
  
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