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Featured researches published by Claudio Ceconi.


European Heart Journal | 2012

2012 focused update of the ESC Guidelines for the management of atrial fibrillation

A. John Camm; Gregory Y.H. Lip; Raffaele De Caterina; Irene Savelieva; Dan Atar; Stefan H. Hohnloser; Gerhard Hindricks; Paulus Kirchhof; Jeroen J. Bax; Helmut Baumgartner; Claudio Ceconi; Veronica Dean; Christi Deaton; Robert Fagard; Christian Funck-Brentano; David Hasdai; Arno W. Hoes; Juhani Knuuti; Philippe Kolh; Theresa McDonagh; Cyril Moulin; Bogdan A. Popescu; Željko Reiner; Udo Sechtem; Per Anton Sirnes; Michal Tendera; Adam Torbicki; Alec Vahanian; Stephan Windecker; Panos E. Vardas

ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American–Australian–African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association ANDROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d. for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid (ASA) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospective, randomized, double-blind, Active-controlled, superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die (twice daily) b.p.m. : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled)-Vascular disease, Age 65–74, Sex category (female) CHADS2 : Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke (doubled) CI : confidence interval CRAFT : Controlled Randomized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : Randomized Double blind trIal to evaluate efficacy and safety of drOnedarone (400 mg b.i.d.) vs . amiodaroNe (600 mg q.d. for 28 daYS, then 200 mg qd thereafter) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v. : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d. : omni die (every day) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of standard therapy PCI : percutaneous coronary intervention PREVAIL : Prospective Randomized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : Randomized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d. : ter in die (three times daily) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on …


European Journal of Heart Failure | 2016

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure : The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC

Piotr Ponikowski; Adriaan A. Voors; Stefan D. Anker; Héctor Bueno; John G.F. Cleland; Andrew J.S. Coats; Volkmar Falk; José Ramón González-Juanatey; Veli Pekka Harjola; Ewa A. Jankowska; Mariell Jessup; Cecilia Linde; Petros Nihoyannopoulos; John Parissis; Burkert Pieske; Jillian P. Riley; Giuseppe Rosano; Luis M. Ruilope; Frank Ruschitzka; Frans H. Rutten; Peter van der Meer; Gerasimos Filippatos; John J.V. McMurray; Victor Aboyans; Stephan Achenbach; Stefan Agewall; Nawwar Al-Attar; John Atherton; Johann Bauersachs; A. John Camm

Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chairperson) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK), Volkmar Falk (Germany), José Ramón González-Juanatey (Spain), Veli-Pekka Harjola (Finland), Ewa A. Jankowska (Poland), Mariell Jessup (USA), Cecilia Linde (Sweden), Petros Nihoyannopoulos (UK), John T. Parissis (Greece), Burkert Pieske (Germany), Jillian P. Riley (UK), Giuseppe M. C. Rosano (UK/Italy), Luis M. Ruilope (Spain), Frank Ruschitzka (Switzerland), Frans H. Rutten (The Netherlands), Peter van der Meer (The Netherlands)


European Journal of Heart Failure | 2012

ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaborati

John J.V. McMurray; Stamatis Adamopoulos; Stefan D. Anker; Angelo Auricchio; Michael Böhm; Kenneth Dickstein; Volkmar Falk; Gerasimos Filippatos; Miguel A. Gomez-Sanchez; Tiny Jaarsma; Lars Køber; Gregory Y.H. Lip; Aldo P. Maggioni; Alexander Parkhomenko; Burkert Pieske; Bogdan A. Popescu; Per K. Rønnevik; Frans H. Rutten; Juerg Schwitter; Petar Seferovic; Janina Stępińska; Pedro T. Trindade; Adriaan A. Voors; Faiez Zannad; Andreas M. Zeiher; Jeroen J. Bax; Helmut Baumgartner; Claudio Ceconi; Veronica Dean; Christi Deaton

Authors/Task Force Members: John J.V. McMurray (Chairperson) (UK)*, Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Angelo Auricchio (Switzerland), Michael Bohm (Germany), Kenneth Dickstein (Norway), Volkmar Falk (Switzerland), Gerasimos Filippatos (Greece), Cândida Fonseca (Portugal), Miguel Angel Gomez-Sanchez (Spain), Tiny Jaarsma (Sweden), Lars Kober (Denmark), Gregory Y.H. Lip (UK), Aldo Pietro Maggioni (Italy), Alexander Parkhomenko (Ukraine), Burkert M. Pieske (Austria), Bogdan A. Popescu (Romania), Per K. Ronnevik (Norway), Frans H. Rutten (The Netherlands), Juerg Schwitter (Switzerland), Petar Seferovic (Serbia), Janina Stepinska (Poland), Pedro T. Trindade (Switzerland), Adriaan A. Voors (The Netherlands), Faiez Zannad (France), Andreas Zeiher (Germany).


European Heart Journal | 2011

ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC)

Vera Regitz-Zagrosek; Carina Blomström Lundqvist; Claudio Borghi; Renata Cifkova; Rafael Ferreira; Jean-Michel Foidart; J. Simon R. Gibbs; Christa Gohlke-Baerwolf; Bulent Gorenek; Bernard Iung; Mike Kirby; Angela H. E. M. Maas; Joao Morais; Petros Nihoyannopoulos; Petronella G. Pieper; Patrizia Presbitero; Jolien W. Roos-Hesselink; Maria Schaufelberger; Ute Seeland; Lucia Torracca; Jeroen Bax; Angelo Auricchio; Helmut Baumgartner; Claudio Ceconi; Veronica Dean; Christi Deaton; Robert Fagard; Christian Funck-Brentano; David Hasdai; Arno W. Hoes

Table 1. Classes of recommendation Table 2. Levels of evidence Table 3. Estimated fetal and maternal effective doses for various diagnostic and interventional radiology procedures Table 4. Predictors of maternal cardiovascular events and risk score from the CARPREG study Table 5. Predictors of maternal cardiovascular events identified in congential heart diseases in the ZAHARA and Khairy study Table 6. Modified WHO classification of maternal cardiovascular risk: principles Table 7. Modified WHO classification of maternal cardiovascular risk: application Table 8. Maternal predictors of neonatal events in women with heart disease Table 9. General recommendations Table 10. Recommendations for the management of congenital heart disease Table 11. Recommendations for the management of aortic disease Table 12. Recommendations for the management of valvular heart disease Table 13. Recommendations for the management of coronary artery disease Table 14. Recommendations for the management of cardiomyopathies and heart failure Table 15. Recommendations for the management of arrhythmias Table 16. Recommendations for the management of hypertension Table 17. Check list for risk factors for venous thrombo-embolism Table 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancy Table 19. Risk groups according to risk factors: definition and preventive measures Table 20. Recommendations for the prevention and management of venous thrombo-embolism in pregnancy and puerperium Table 21. Recommendations for drug use ABPM : ambulatory blood pressure monitoring ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AHA : American Heart Association aPTT : activated partial thromboplastin time ARB : angiotensin receptor blocker AS : aortic stenosis ASD : atrial septal defect AV : atrioventricular AVSD : atrioventricular septal defect BMI : body mass index BNP : B-type natriuretic peptide BP : blood pressure CDC : Centers for Disease Control CHADS : congestive heart failure, hypertension, age (>75 years), diabetes, stroke CI : confidence interval CO : cardiac output CoA : coarction of the aorta CT : computed tomography CVD : cardiovascular disease DBP : diastolic blood pressure DCM : dilated cardiomyopathy DVT : deep venous thrombosis ECG : electrocardiogram EF : ejection fraction ESC : European Society of Cardiology ESH : European Society of Hypertension ESICM : European Society of Intensive Care Medicine FDA : Food and Drug Administration HCM : hypertrophic cardiomyopathy ICD : implantable cardioverter-defibrillator INR : international normalized ratio i.v. : intravenous LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction LVOTO : left ventricular outflow tract obstruction MRI : magnetic resonance imaging MS : mitral stenosis NT-proBNP : N-terminal pro B-type natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulant PAH : pulmonary arterial hypertension PAP : pulmonary artery pressure PCI : percutaneous coronary intervention PPCM : peripartum cardiomyopathy PS : pulmonary valve stenosis RV : right ventricular SBP : systolic blood pressure SVT : supraventricular tachycardia TGA : complete transposition of the great arteries TR : tricuspid regurgitation UFH : unfractionated heparin VSD : ventricular septal defect VT : ventricular tachycardia VTE : venous thrombo-embolism WHO : World Health Organization Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the …


European Heart Journal | 2009

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery

Don Poldermans; Jeroen J. Bax; Eric Boersma; Stefan De Hert; Erik Eeckhout; Gerry Fowkes; Bulent Gorenek; Michael G. Hennerici; Bernard Iung; Malte Kelm; Keld Kjeldsen; Steen Dalby Kristensen; Jose Lopez-Sendon; Paolo Pelosi; François Philippe; Luc Pierard; Piotr Ponikowski; Jean-Paul Schmid; Olav F.M. Sellevold; Rosa Sicari; Greet Van den Berghe; Frank Vermassen; Sanne E. Hoeks; Ilse Vanhorebeek; Alec Vahanian; Angelo Auricchio; Claudio Ceconi; Veronica Dean; Gerasimos Filippatos; Christian Funck-Brentano

The American College of Cardiology, American Heart Association, and the European Society of Cardiology are all in the process of completing updated versions of our Guidelines for Perioperative Care. Our respective writing committees are undertaking a careful analysis of all relevant validated studies and always incorporate appropriate new trials and meta-analyses into our evidence review. In the interim, our current joint position is that the initiation of beta blockers in patients who will undergo non-cardiac surgery should not be considered routine, but should be considered carefully by each patients treating physician on a case-by-case basis. Please see the expression of concern which is free to view in Eur Heart J (2013) 34 (44): 3460; doi: 10.1093/eurheartj/eht431. AAA : abdominal aortic aneurysm ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AHA : American Heart Association AR : aortic regurgitation ARB : angiotensin receptor blocker AS : aortic stenosis AF : atrial fibrillation BBSA : β-blocker in spinal anaesthesia BNP : brain natriuretic peptide CABG : coronary artery bypass grafting CARP : coronary artery revascularization prophylaxis CASS : coronary artery surgery study CI : confidence interval COX-2 : cyclooxygenase-2 COPD : chronic obstructive pulmonary disease CPET : cardiopulmonary exercise testing CPG : Committee for Practice Guidelines CRP : C-reactive protein CT : computed tomography cTnI : cardiac troponin I cTnT : cardiac troponin T CVD : cardiovascular disease DECREASE : Dutch Echocardiographic Cardiac Risk Evaluating Applying Stress Echo DES : drug-eluting stent DIPOM : Diabetes Postoperative Mortality and Morbidity DSE : dobutamine stress echocardiography ECG : electrocardiography ESC : European Society of Cardiology FEV1 : forced expiratory volume in 1 s FRISC : fast revascularization in instability in coronary disease HR : hazard ratio ICU : intensive care unit IHD : ischaemic heart disease INR : international normalized ratio LMWH : low molecular weight heparin LQTS : long QT syndrome LR : likelihood ratio LV : left ventricular MaVS : metoprolol after surgery MET : metabolic equivalent MI : myocardial infarction MR : mitral regurgitation MRI : magnetic resonance imaging MS : mitral stenosis NICE-SUGAR : normoglycaemia in intensive care evaluation and survival using glucose algorithm regulation NSTEMI : non-ST-segment elevation myocardial infarction NT-proBNP : N-terminal pro-brain natriuretic peptide NYHA : New York Heart Association OPUS : orbofiban in patients with unstable coronary syndromes OR : odds ratio PaCO2 : mixed expired volume of alveolar and dead space gas PAH : pulmonary arterial hypertension PETCO2 : end-tidal expiratory CO2 pressure PCI : percutaneous coronary intervention PDA : personal digital assistant POISE : PeriOperative ISchaemic Evaluation trial QUO-VADIS : QUinapril On Vascular ACE and Determinants of ISchemia ROC : receiver operating characteristic SD : standard deviation SMVT : sustained monomorphic ventricular tachycardia SPECT : single photon emission computed tomography SPVT : sustained polymorphic ventricular tachycardia STEMI : ST-segment elevation myocardial infarction SVT : supraventricular tachycardia SYNTAX : synergy between percutaneous coronary intervention with taxus and cardiac surgery TACTICS : treat angina with aggrastat and determine cost of therapy with an invasive or conservative strategy TIA : transient ischaemic attack TIMI : thrombolysis in myocardial infarction TOE : transoesophageal echocardiography UFH : unfractionated heparin VCO2 : carbon dioxide production VE : minute ventilation VHD : valvular heart disease VKA : vitamin K antagonist VO2 : oxygen consumption VPB : ventricular premature beat VT : ventricular tachycardia Guidelines and Expert Consensus Documents aim to present management and recommendations based on the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient suffering from a specific condition, taking into account not only the impact on outcome, but also the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.1 A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and also by other organizations or related societies. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC guidelines and Expert Consensus Documents can be found on the ESC website in the guidelines section (www.escardio.org). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. …


Circulation | 1990

Occurrence of oxidative stress during reperfusion of the human heart.

Roberto Ferrari; Ottavio Alfieri; Salvatore Curello; Claudio Ceconi; Anna Cargnoni; P. Marzollo; Alessandro Pardini; Eugenio Caradonna; O. Visioli

We have investigated the relation between occurrence of myocardial oxidative stress and functional recovery during postischemic reperfusion in 20 selected patients subjected to aortocoronary bypass grafting. Patients were selected for having normal percent ejection fraction and left ventricular end-diastolic pressure before the operation. Occurrence of oxidative stress was assessed by measuring the formation and release of oxidized glutathione (GSSG) in the coronary sinus immediately before aortic cross-clamp, 1, 5, 10, and 20 minutes after removal of aortic cross-clamp, and 10 and 20 minutes after the end of cardiopulmonary bypass. Reduced glutathione (GSH), lactate, and creatine phosphokinase release were also monitored with the same timing. Standard hemodynamic measurements were recorded by means of a triple-lumen thermodilution pulmonary artery catheter before sternotomy, 15 minutes after the end of cardiopulmonary bypass, and during the 24 hours after termination of cardiopulmonary bypass. Reperfusion in patients after a short period of ischemia (less than 30 minutes; group 1) resulted in a small and transient release in the coronary sinus of GSSG and GSH and in a progressive improvement of hemodynamic parameters reaching a stable state 4 hours after the operation. In patients with a period of ischemia longer than 30 minutes (group 2), reperfusion induced a marked and sustained release of lactate, GSH, and GSSG; the arteriocoronary sinus difference for GSSG was still negative after the end of cardiopulmonary bypass. The arteriocoronary sinus difference for creatine phosphokinase also remained negative for as long as 20 minutes after cardiopulmonary bypass, and the rate of functional recovery was significantly delayed, reaching the values of group 1 only 12 hours after the operation. In these patients there was a positive correlation (r = 0.88, p less than 0.01) between the duration of ischemia and the myocardial arteriovenous difference for GSSG. In addition, there was a negative correlation between the arteriocoronary sinus difference for GSSG and cardiac index measured 2, 4, and 6 hours after the operation. These data suggest for the first time that, depending on the severity of the ischemic period, oxidative stress occurs during reperfusion of patients with coronary artery disease who are subjected to heart surgery and that it may be linked with a delay in postoperative recovery of cardiac function.


The American Journal of Medicine | 1991

Oxygen free radicals and myocardial damage: protective role of thiol-containing agents.

Roberto Ferrari; Claudio Ceconi; S. Curello; Anna Cargnoni; Ottavio Alfieri; Alessandro Pardini; P. Marzollo; O. Visioli

It has been suggested that the sudden presence of oxygen during reperfusion after a period of ischemia may be toxic for the myocardial cell. The oxygen molecule is capable of producing reactions in the cell, forming highly reactive free radicals, and inducing lipid peroxidation of membranes, altering their integrity and increasing their fluidity and permeability. The ischemic and reperfused cardiac cell is the prime candidate for this reaction sequence and may explain the molecular mechanism underlying the pathologic events related to membrane dysfunction and calcium homeostasis. However, the myocardium has a series of defense mechanisms including the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase plus other endogenous antioxidants such as vitamin E, ascorbic acid, and cysteine to protect the cell against the cytotoxic oxygen metabolites. The prerequisite for oxygen free radical involvement in ischemia and reperfusion damage is that ischemia alters the defense mechanisms against oxygen toxicity. It is known that ischemia may impair mitochondrial SOD and, with reperfusion, oxidative stress may occur as shown by tissue accumulation and release of oxidized glutathione. This tripeptide molecule in the cofactor of glutathione peroxidase, the enzyme that removes hydrogen and lipid peroxides. Its formation and subsequent release is a reliable index of oxidative damage. In our study, we investigated the effects of N-acetylcysteine on oxidative damage in the isolated rabbit heart. N-acetylcysteine increases, in a dose-dependent manner (from 10(-7) to 10(-5) M), the myocardial glutathione content and provides an important degree of protection against ischemia and reperfusion. Oxidative stress does not occur, mitochondrial function is maintained, enzyme release is reduced, and contractile recovery is increased. Similarly, we administered N-acetylcysteine in the pulmonary artery of coronary artery disease patients undergoing coronary bypass grafting (150 mg/kg in 1 hour followed by 150 mg/kg in 4 hours). The degree of oxidative stress on reperfusion was reduced and recovery of cardiac function improved. In this article, we review the cardioprotective role of thiol-containing agents.


Heart | 2000

Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes

Giorgio Vescovo; Maurizio Volterrani; Roberta Zennaro; Marco Sandri; Claudio Ceconi; R Lorusso; Roberto Ferrari; G. Ambrosio; L. Dalla Libera

OBJECTIVE To investigate the contribution of apoptosis in the development of the skeletal myopathy in chronic heart failure. DESIGN The electrophoretic pattern of myosin heavy chains (MHC), fibre cross sectional area, number of in situ nick end labelling (TUNEL) positive apoptotic myocyte nuclei, and the tissue levels of caspase-3, Bcl-2, and ubiquitin were determined in biopsies taken from the vastus lateralis muscle. The study involved nine patients with severe chronic heart failure caused by ischaemic heart disease and hibernating myocardium and five controls. RESULTS In chronic heart failure patients the vastus lateralis showed a significant increase of MHC2a and MHC2b and a greater degree of fibre atrophy, as demonstrated by the decreased cross sectional area. There was also an increased number of TUNEL positive apoptotic myocyte nuclei. Tissue concentrations of Bcl-2 were decreased, while those of caspase-3 and ubiquitin were increased. Peak oxygen consumption (Vo 2) was negatively correlated with the number of TUNEL positive nuclei and the fibre cross sectional area. There was a correlation between the number of apoptotic nuclei and the fibre cross sectional area, but no correlation between myosin heavy chains and number of apoptotic nuclei. CONCLUSIONS Myocyte apoptosis occurs in the skeletal muscle of patients with chronic heart failure, and its magnitude is associated with the severity of exercise capacity limitation and the degree of muscle atrophy. Muscle atrophy contributes to the limitation of exercise capacity, together with the increased synthesis of fast, more fatiguable myosin heavy chains.


Journal of Molecular and Cellular Cardiology | 1987

The role of glutathione status in the protection against ischaemic and reperfusion damage: effects of N-acetyl cysteine.

Claudio Ceconi; Salvatore Curello; Anna Cargnoni; Roberto Ferrari; Alberto Albertini; O. Visioli

It is known that myocardial ischaemia causes a marked decline of cellular thiol pool and of protein sulphydryl groups content. Reperfusion under these conditions results in oxydative damage which is concomitant with poor recovery of mechanical function. We have evaluated the role of glutathione status in the protection against ischaemic and reperfusion damage by treating the isolated rabbit hearts with N-acetylcysteine (10(-6) M), a sulphydryl group donor. Ischaemic and reperfusion damage was determined in terms of mechanical function, rate of lactate and creatine kinase (CPK) release, mitochondrial function and tissue content of reduced (GSH) and oxidized (GSSG) glutathione and of protein sulphydryl groups (SH). After 60 mins of ischaemia (induced by reducing coronary flow from 24 to 1 ml/min) followed by 30 mins of reperfusion there was an increase of diastolic pressure to 51.6 +/- 3.5 mmHg with only a 22% recovery of systolic pressure, massive CPK release and a deterioration in mitochondrial function. Tissue contents of GSH and of protein SH were severely decreased, while those of GSSG were increased. The GSH/GSSG ratio was reduced from the aerobic value of 50 to 13.4, suggesting that an oxidative stress has occurred. N-acetylcysteine infused for 60 mins before ischaemia determined a 38% increase in tissue content of GSH with no major changes of GSSG or protein SH. The ischaemic-induced decrease of GSH and protein SH was also limited by pretreatment with N-acetylcysteine and there was no accumulation of GSSG after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Circulation | 2005

Tumor Necrosis Factor-α Receptor 1 Is a Major Predictor of Mortality and New-Onset Heart Failure in Patients With Acute Myocardial Infarction The Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) Study

Marco Valgimigli; Claudio Ceconi; Patrizia Malagutti; Elisa Merli; Olga Soukhomovskaia; Gloria Francolini; Giordano Cicchitelli; Adriana Olivares; Giovanni Parrinello; Gianfranco Percoco; Gabriele Guardigli; Donato Mele; Roberto Pirani; Roberto Ferrari

Background—Tumor necrosis factor alpha-&agr; (TNF-&agr;) activation is an independent prognostic indicator of mortality in patients with heart failure (HF). Despite the recognition that several TNF family cytokines are elevated during myocardial infarction, their role in predicting subsequent prognosis in these setting remains poorly understood. Methods and Results—We performed a systematic evaluation of TNF-&agr; and its type 1 and 2 soluble receptors, together with interleukin (IL)-6, IL-1 receptor antagonist, and IL-10, in 184 patients (132 men; mean age, 64±12) consecutively admitted for myocardial infarction. We correlated their values to short- and long-term incidence of death and HF (primary outcome). In 10 patients, we also studied the presence of transcardiac gradients for TNF-&agr; and its soluble receptors. The control group comprised 45 healthy subjects who were sex and age matched (33 men; mean age, 65±6 years) to the patients. All tested cytokines were increased in patients, and no transcardiac or systemic AV difference was found. After a median follow-up of 406 days (range, 346 to 696 days), 24 patients died and 32 developed HF. Univariate analysis showed that all cytokines were related to outcome, whereas after adjustment for baseline and clinical characteristics, sTNFR-1 remained the only independent predictor of death and HF (hazard ratio, 2.9; 95% CI, 1.9 to 3.8, tertile 1 versus 3), together with left ventricular ejection fraction, Killip class, and creatine kinase-MB at peak. Conclusions—sTNFR-1 is a major short- and long-term predictor of mortality and HF in patients with acute myocardial infarction.

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Jeroen J. Bax

Erasmus University Medical Center

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