28/01/2012   Brain tumours among interventional cardiologists: a cause for alarm?   Report of four new cases from two cities and a review of the literature Ariel Roguin1*, MD, PhD; Jacob Goldstein2, MD; Olivier Bar3, MD 1. Interventional Cardiology, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, the Technion, Israel Institute of Technology, Haifa, Israel; 2. Cardiology Department Carmel Medical Center, Haifa, Israel; 3. Cardiologie Interventionnelle Imagerie Cardiaque, Clinique Saint-Gatien, Tours, France *Corresponding author: Department of Cardiology, Rambam Medical Center, B. Rappaport, Faculty of Medicine Technion, Israel Institute of Technology, Haifa 31096, Israel. E-mail: aroguin@technion.ac.il Abstract Aims: Interventional cardiologists who work in cardiac catheterisation laboratories are exposed to low doses of ionising radiation that could pose a health hazard. DNA damage is considered to be the main initiating event by which radiation damage to cells results in development of cancer. Methods and results: We report on four interventional cardiologists, all with brain malignancies in the left hemisphere. In a literature search, we found five additional cases and thus present data on six interventional cardiologist and three interventional radiologists who were diagnosed with brain tumours. All worked for prolonged periods with exposure to ionising radiation in the catheterisation laboratory. Conclusions: In interventional cardiologists and radiologists, the left side of the head is known to be more exposed to radiation than the right. A connection to occupational radiation exposure is biologically plausible, but risk assessment is difficult due to the small population of interventional cardiologists and the low inci-dence of these tumours. This may be a chance occurrence, but the cause may also be radiation exposure. Scientific study further delineating occupational risks is essential. Since interventional cardiologists have the highest radiation exposure among health professionals, major awareness of radiation safety and training in radiological protection are essential and imperative, and should be used in every procedure. EuroIntervention 2012;7:1081-1086

 24/01/2012   Silent Ischemia: Clinical Relevance   Myocardial ischemia can occur without overt symptoms. In fact, asymptomatic (or silent) ST-segment depression during ambulatory electrocardiogram monitoring occurs more often than symptomatic ST-segment depression in patients with coronary artery disease. Initial studies documented that silent ischemia provided independent pre-diction of adverse outcomes in patients with known and unknown coronary artery disease. The ACIP (Asymptom-atic Cardiac Ischemia Pilot Study) enrolled patients in the 1990s and found that revascularization was better than medical therapy in reducing silent ischemic episodes and possibly cardiovascular (CV) events. However, the more recent COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found similar CV event rates between patients treated with optimal medical therapy alone and those treated with opti-mal medical therapy plus percutaneous revascularization. Therefore, in the current era, medical therapy appears to be as effective as revascularization in suppressing symptomatic ischemia and preventing CV events. COURAGE w a s not designed to evaluate changes in the frequency of silent ischemia. Therefore, silent ischemia may persist de-spite current-era treatment and might still identify patients with increased risk of CV events. Also, silent isch-emia is likely to occur frequently in heart transplant patients with denervated hearts and coronary allograft vas-culopathy, and future study aimed at improving the management of silent ischemia in this population is warranted. Additionally, future research is warranted to study the effect of newer medical therapies such as ra-nolazine or selected use of revascularization (for example, guided by fractional flow reserve) in those patients with persistent silent ischemia despite optimal current-era medical therapy. (J Am Coll Cardiol 2012;59: 435–41) © 2012 by the American College of Cardiology Foundation

 20/01/2012   Anaemia in heart failure: intravenous iron therapy   Intravenous iron has emerged as a well tolerated and effective therapy to improve symptoms and quality of life in both anaemic and non-anaemic heart failure patients with iron deficiency. Iron deficiency can be easily detected with simple laboratory tests. Authors: Peraira-Moral J. Roberto, Núñez-Gil Ivan J. Background Anaemia, although common in heart failure patients, reduces functional status, quality of life and is an independent risk factor for hospital admissions and mortality (1,2). Intravenous iron therapy benefits these patients and provides cardiologists with a means for more accurate management. Prevalence of anaemia in heart failure (HF) patients depending on the defining criteria that is used, ranges from 7 to over 50% (3). Indeed, the World Health Organisation holds a haemoglobin (Hb) concentration under 13 g/dl in men and 12 g/dl in women as aneamia whereas the National Kidney Foundation defines anaemia as Hb < 12 g/dl in men and postmenopausal women. Anaemia is always more frequent in older patients, advanced HF, chronic renal failure, in females and African-Americans (3) - regardless or whether heart failure is systolic or diastolic. Multiple mechanisms have been identified as causes (4). Iron deficiency (ID) appears most important, followed by gastrointestinal absorption, increased macrophage iron storage and gastrointestinal bleeding. These factors may contribute to ID and ultimately, lead to anaemia. I - Diagnostic testing Routine diagnostic evaluation (1,5) includes: • Complete blood count with reticulocyte count and index • Serum iron and total iron binding capacity • Transferrin saturation • Ferritin • Serum B12 and folate • Thyroid stimulating hormone • Fecal occult blood test Red blood cell distribution width is a numerical measure of the variability in the size of circulating erythrocytes, taken during a standard blood count test. Ineffective erythropoiesis causes heterogeneity in erythrocytes size and a higher RDW. RDW has recently emerged as a new prognostic marker of HF, regardless of Hb levels (6). II - Prognostic implications Many studies have shown anaemia to increase mortality and morbidity in HF patients (1, 5, 8, 9) and to cause the following: • Higher NYHA functional class • Decreased exercise capacity (shorter distance covered during 6-minute walking test, lower peak-oxygen consumption during cardiopulmonary exercise testing) • Decreased renal function • Lower quality of life • Increased HF admissions III - Management options Current HF guidelines (1,2) have not fully established specific routine treatment. Blood transfusion is useful in critically ill patients with chronic cardiac disease and Hb less than 7 g/dl (10). However, blood transfusion is not recommended as long-term therapy because of associated risks, such as infection, HLA sensibilisation and iron overload (11). Impaired erythropoiesis is one of the mechanisms of anaemia in HF. Erythropoietin-stimulating agents (ESA) have been studied in the past decade in combined heart failure and anemia patients and it was found that ESA are associated with a reduction in HF hospitalisations and improvement in exercise tolerance, quality of life, brain-natriuretic peptide levels and left ventricular ejection fraction (12). Recently, intravenous iron therapy has been successfully incorporated into management of patients with HF, as well. Oral iron formulation are used for ID treatment. Nevertheless, poor absortion and gastrointestinal intolerance are common. Intravenous iron preparations used in these patients mainly are 1) iron sucrose (alone or combined with ESA) and 2) iron carboxymaltose. Intravenous iron sucrose Two studies showed improvement in Hb level, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score and 6-minute walk test distance (13, 14). In the very recent FERRIC-HF trial (15), 35 HF patients (NYHA class II or III) with ID treated with iron sucrose (200 mg weekly until ferritin > 500 ng/ml, 200 mg monthly thereafter) improved their exercise capacity and symptom status. These benefits were more evident in anaemic patients. Intravenous iron sucrose can be administered either as slow injection (over 10 minutes) or by infusion (11). Total iron dose required for iron repletion is calculated using the Ganzoni formula (body weight (kg) x 2.4 x [15 – patient's Hb (g/dl)] + 500 mg for stores). This treatment is usually well tolerated. Main side effects are taste disturbances, while less common side effects are nausea, vomiting, abdominal pain, diarrhoea, flushing, bronchospasm, fever, myalgia and injection site reactions. Intravenous iron carboxymaltose Ferric carboxymaltose (FCM) consists of a ferric hydroxide core stabilised by a carbohydrate shell (16) that allows for controlled delivery of iron to target tissues. Several randomised trials have shown that intravenous FCM rapidly improves Hb levels and replenishes depleted iron stores in patients with ID anaemia, including, for example, those with chronic kidney disease (17). FCM is administered via drip infusion (up to a maximum single dose of 1000 mg of iron, but not exceeding 15 mg/kg or the calculated cumulative dose) or bolus injection - at a maximum single dose of up to 200 mg of iron up to three times per week (16). Anker et al (18) studied the effects of intravenous FCM versus placebo in 459 HF patients (left ventricular ejection fraction of 45 % or less, NYHA class II or III) with ID. Self-Reported Patient Global Assessment, NYHA class, 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score improved in the group treated with FCM. FCM is well tolerated. Most adverse effects associated with this treatment are mild to moderate in severity, and include gastrointestinal disturbances, dizziness, rash and injection-site reactions (16). IV - Intravenous iron therapy in non-anaemic heart failure patients A large, recent study (19) found that ID (ferritin <100 μg/l, or ferritin 100–300 μg/l with transferrin saturation <20%) is present in 37% of stable chronic systolic HF patients. Iron deficiency was more prevalent in women, mostly with NYHA class IV, higher N-terminal pro-type B natriuretic peptide and C-reactive protein levels. Regarding outcome, a multivariable analysis showed that ID was associated with increased risk of death or heart transplantation, irrespective of the presence of anaemia. Authors suggest that iron supplementation could be considered to improve prognosis of all HF patients with ID. Benefit of iron supplementation was later analysed in the FERRIC-HF trial which found that non-anaemic iron-deficient HF patients had less benefit from intravenous iron sucrose than anaemic patients (15) whereas in the FAIR-HF trial, the patients receiving ferric carboxymaltose showed similar symptoms, 6-minute walk test distance, and quality of life improvements whether anaemic or non-anaemic HF patients (18). Conclusion Anaemia is a common and multifactorial condition associated with poor outcome in HF patients. One of the main causes of anaemia is ID. Iron deficiency can be easily detected with simple laboratory tests. Intravenous iron has emerged as a well tolerated and effective therapy to improve symptoms and quality of life in both anaemic and non-anaemic HF patients with iron deficiency. Nevertheless, larger-scale and longer-term studies are necessary to confirm the safety and efficacy of this therapy in HF patients, especially in those without anaemia. References 1) Dickstein K, Cohen-Solal A, Filippatos G, et al. Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J 2008;29:2388-2442 2) Lindenfeld JA, Albert NM, Boehmer JP, et al. Executive Summary: HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Cardiac Fail 2010;16:475-539 3) Stamos TD, Silver MA. Management of anemia in heart failure. Curr Opin Cardiol 2010;25:148-154 4) Drakos SG, Anastasiou-Nana MI, Malliaras KG, Nanas JN. Anemia in Chronic Heart Failure. Congest Heart Fail 2009;15:87-92. 5) Ezekowitz JA, McDonald MA. Management of comorbidity in chronic heart failure. In: Greenberg BH, Barnard DD, Narayan SM, Teerlink JR, eds. Management of Heart Failure. Chichester, Wiley-Blackwell; 2010; 137-156 6) Pascual-Figal DA, Bonaque JC, Redondo B, et al. Red blood cell distribution width predicts long-term outcome regardless of anaemia status in acute heart failure patients. Eur J Heart Fail 2009;11:840-846 7) Wians FH, Urban JE, Keffer JH, Kroft SH. Discriminating Between Iron Deficiency Anemia and Anemia of Chronic Disease Using Tradicional Indices of Iron Status vs Transferrin Receptor Concentration. Am J Clin Pathol 2001;115:112-118. 8) Anand IS. Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol 2008;52:501-511. 9) He SW, Wang LX. The Impact of Anemia on the Prognosis of Chronic Heart Failure. A Meta-Analysis and Systemic Review. Congest Heart Fail 2009;15:123-130. 10) Hébert PC, Tinmouth A, Corwin HL. Controversies in RBC Transfusion in Critically Ill. Chest 2007;131:1583-1590. 11) Mak G, Murphy NF, McDonald K. Anemia in Heart Failure: to Treat or not to Treat? Curr Treat Options Cardiovasc Med 2008;10:455-464. 12) Lawler PR, Filion KB, Eisenberg MJ. Correcting Anemia in Heart Failure: The Efficacy and Safety of Erithropoiesis-Stimulating Agents. J Cardiac Fail 2010;16:649-658. 13) Bolger AP, Bartlett FR, Penston HS, et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol 2006;48:1225-1227. 14) Toblli JE, Lombraña A, Duarte P, et al. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol 2007;50:1657-1665. 15) Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and Iron Deficiency. FERRIC-HF: A Randomized, Controlled, Observer-Blinded Trial. J Am Coll Cardiol 2008,51:103-112. 16) Lyseng-Williamson KA, Keating GM. Ferric carboxymaltose. A Review of its Use in Iron-Deficiency Anaemia. Drugs 2009;69:739-756. 17) Schaefer RM, Khasabov NN, Todorov NG, et al. The efficacy and safety of intravenous ferric carboxymaltose compared to iron sucrose in haemodialysis patients with iron deficiency anaemia [abstract no. MP375 plus poster]. 45th Congress of the European Renal Association and the European Dialysis and Transplant Association; 2008 May 10-13; Stockholm. 18) Anker SD, Comin Colet J, Filippatos G, et al. Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency. N Engl J Med 2009;361:2436-2448 19) Jankowska EA, Rozentryt P, Witkowska A, et al. Iron deficiency: an ominous sign in patients with systolic heart failure. Eur Heart J 2010;31:1872-1880. The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

 15/01/2012  Subclinical Atrial Fibrillation and the Risk of Stroke   A b s t r a c t Background One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted de-vices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. Methods We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been im-planted. We monitored the patients for 3 months to detect subclinical atrial tachyar-rhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. Results By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P = 0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhyth-mias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P = 0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. Conclusions Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred fre-quently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.) (n engl j med 366;2 nejm.org january 12 , 2012)

 07/01/2012   Angina Pectoris   The remarkable facts, that the paroxysm, or indeed the disease itself, is excited more especially upon walking up hill, and after a meal; that thus excited, it is accompanied with a sensation, which threatens instant death if the motion is persisted in; and, that on stopping, the distress immedi-ately abates, or altogether subsides; have . . . formed a constituent part of the character of Angina Pectoris Warren J. Remarks on angina pecto-ris. N Engl J Med Surg 1812;1:1-11

 10/12/2011   What to do in symptomatic drug-refractory permanent atrial fibrillation?   Biventricular pacing following atrioventricular junction catheter ablation in uncorrected atrial fibrillation despite RV pacing, or in severe cases of atrial fibrillation - with heart failure, depressed ejection fraction or wide QS -, are effective therapy in patients with uncontrolled and permanent atrial fibrillation. Incidence of atrial fibrillation per 1000 person-years is 3.1 and 1.9 in 64-year-old men and women respectively, 19.2 in the 65-74 age bracket, and 31.4 in the over 80 population, which in Europe, roughly equates to six million and three and a half in the US, and figures are expected to rise as the population continues to age (1,2,3). Sixty percent of these have a permanent form of it, and forty per cent of these patients display severe symptoms, patients with uncontrolled congestive heart failure included. The initial challenge is to properly detect patients who could benefit from AV junction ablation and pacing. In a prospective, observational, transversal study on the management of AF as primary diagnosis in Italy, we enrolled consecutive in- and out-patients referred to 43 different cardiology departments (4). Although it was observed that atrioventricular (AV) junction ablation and pace-maker implantation had been indicated in 8.6% of patients according to class I indication of Italian guidelines (5) only 2.7% were recommended the intervention by the attending cardiologist. Study results reflect the portion of the physician body who might not refer for intervention because they consider that AV junction ablation merely a palliative or even a potentially harmful. According to guidelines (5), the patients candidates to AV junction ablation are those who: 1) due to high and irregular ventricular rate, had severe symptoms of palpitations, fatigue and shortness of breath during physical activity and at rest with chest discomfort greatly impairing quality of life; Or 2) having a CRT indication due to drug-refractory heart failure, depressed left ventricular (LV) function and wide QRS complexes, have the need to avoid competitive atrial rhythm in order to assure a constant biventricular pacing In fact, randomised observational studies from the last two decades having enrolled in total over a thousand patients have shown that, AV junction ablation and permanent pacing from the RV apex provide efficient rate control, regularisation of AF and improve symptoms without deterioration of the ventricular function (6-13). In a recent sub-analysis of the APAF trial (14), when compared with the pre-ablation evaluation in quality of life scores, great improvement in exercise capacity and cardiac performance was observed at 6 months (Table 1). However, AV junction ablation and permanent right ventricular (RV) pacing cause a non-physiologic asynchronous contraction which might partly counteract any beneficial effects of ablation. Indeed, right ventricular pacing induces a ventricular activation sequence resembling that of left bundle branch block, i.e. the right ventricle is activated before the left, thus causing inter-ventricular dyssynchrony. Likewise, the LV septum is activated before the LV free wall causing intraventricular dyssynchrony. Resynchronisation therapy (CRT) achieved through AV junction ablation can restore proper synchrony. In a sub-analysis on 171 patients of the recent APAF trial (14), 63% of patients had improved clinical conditions, 9% had no change and 28 % worsened with RV pacing during a median follow-up of 20 months. With biventricular pacing however, 83% improved, 5% had no change and 12 % had a worsened clinical condition (p=0.001 versus RV pacing). Furthermore, beneficial effects from CRT were consistent in patients who met the current recommendations from expert consensus for CRT, ejection fraction ≤35%, NYHA class ≥III and QRS width ≥120, (class IIa, level of evidence B), as well as in those who did not. In patients affected by severely symptomatic permanent AF, patients had a greater benefit from AV junction ablation and CRT pacing than RV-paced patients irrespective of the severity of the underlying structural heart disease and of current guidelines criteria. After multivariable analysis, only the CRT mode remained an independent predictor of clinical benefit (p=0.001). As no clinical difference was observed in the outcome of patients treated with biventricular pacing who met the current guideline indications, with those who did not, the results from the APAF study suggest that the indications for CRT should be extended to all patients with severely symptomatic AF undergoing AV junction ablation. Nevertheless, considering the higher costs and complications of CRT, an alternative strategy of CRT upgrading may be a reasonable clinical option in patients who, for any reason, were initially paced at the RV only. “Upgrading” to BiV pacing in patients who developed heart failure months or years after AV junction ablation resulted in a clinical benefit similar to that of “de-novo” CRT pacing (16,17,18). Leon et al (16) had upgraded 20 patients who became severely symptomatic 17 months after AV junction ablation and RV pacing to BiV pacing; they observed an improvement of NYHA class of 29%, of Minnesota LHFQ score of 33% and a reduction of hospitalisation of 81%. Similar results were obtained more recently by Valls-Bertault V et al and by Frohlich G et al (17, 18). In the 2011 APAF sub-analysis (14), upgrade was performed in 14 patients who had developed “clinical failure” after a median of 12 months of RV pacing ; after 3 months, these patients showed a significant reduction in specific AF symptoms and an improvement in cardiac performance similar to that observed in “de novo” CRT pacing. References 1. Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial Fibrillation in a population-based cohort: the Framingham heart study. JAMA 1994; 271: 840±4. 2. Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med 1995; 155: 469-73. 3. Savelieva I, Camm J. Clinical trends in atrial Fibrillation at the turn of the millennium. J Intern Med 2001; 250: 369±372 4. Bottoni N, Tritto M, Ricci R, Accogli M, , Di Biase M, Iacopino S, Iori M, Themistoclakis S, Sitta N, Spadacini G, De Ponti R, Brignole M. Adherence to guidelines for atrial fibrillation management of patients referred to cardiology departments: Studio Italiano multicentrico sul Trattamento della Fibrillazione Atriale (SITAF). Europace 2010; 12, 1070–1077 5. Disertori M, Alboni P, Botto G, Brignole M, Cappucci A, Delise P. Linee Guida AIAC 2006 sul trattamento della fibrillazione atriale. GIAC (Giornale Italiano Aritmologia e Cardiostimolazione) 2006; 9: 1–45. 6. Brignole M, Menozzi C, Gianfranchi L, Musso G, Mureddu R, Bottoni N, Lolli G. Assessment of atrioventricular junction ablation and VVIR pacemaker versus pharmacological treatment in patients with heart failure and chronic atrial fibrillation: a randomized, controlled study. Circulation 1998; 98: 953-960. 7. Brignole M, Gianfranchi L, Menozzi C, Alboni P, Musso G, Bongiorni MG, Gasparini M, Raviele A, Lolli G, Paparella N, Acquarone S. Assessment of atrioventricular junction ablation and DDDR mode-switching pacemaker versus pharmacological treatment in patients with severely symptomatic paroxysmal atrial fibrillation: a randomized controlled study. Circulation 1997;96:2617-2624. 8. Kay GN, Ellenbogen KA, Giudici M, Redfield MM, Jenkins LS, Mianulli M, Wilkoff B. The Ablate and Pace Trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. APT Investigators. J Interv Card Electrophysiol 1998; 2: 121-135. 9. Ozcan C, Jahangir A, Friedman PA, Patel PJ, Munger TM, Rea RF, Lloyd MA, Packer DL, Hodge DO, Gersh BJ, Hammill SC, Shen WK. Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation. N Engl J Med 2001; 344: 1043–1051. 10. Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA. Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis. Circulation 2000; 101: 1138-1144. 11. Tan E, Rienstra M, Wiesfeld AC, Schoonderwoerd BA, Hobbel HH, Van Gelder IC. Long-term outcome of AV node ablation and pacing for symptomatic refractory AF. Europace 2008; 10: 412-8µ 12. Chen L, Hodge D, Jahangir A, Ozcan C, Trusty J, Friedman P, Rea R, Bradley D, Brady P, Hammill S, Hayes D, Shen WK. Preserved left ventricular ejection fraction following atrioventricular junction ablation and pacing for atrial fibrillation. J Cardiovasc Electrophysiol 2008; 19: 19-27 13. Bradley D, Shen WK. Atrioventricular junction ablation combined with either right ventricular pacing or cardiac resynchronization therapy for atrial fibrillation: The need for large-scale randomized trials. Heart Rhythm 2007;4:224 –232 14. Brignole M, Botto GL, Mont L, Oddone D, Iacopino S, De Marchi G, Campoli M, Sebastiani V, Vincenti A, Garcia Medina D, Osca Asensi J, Mocini A, Grovale N, De Santo T, Menozzi C. Predictors of clinical efficacy of “Ablate and Pace” therapy in patients with permanent atrial fibrillation. Heart 2011; 10.1136/heartjnl-2011-301069 (ahead of print) 15. Brignole M, Botto GL, Mont L, Iacopino S, De Marchi G, Oddone D, Luzi M, Tolosana JM, Navazio A, Menozzi C. Cardiac resynchronization therapy in patients undergoing AV Junction ablation for permanent atrial fibrillation: A randomized trial Eur Heart J 2011; 32: 2420–2429 16. Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL, Langberg JJ, DeLurgio DB. Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation: effect of upgrading to biventricular pacing after chronic right ventricular pacing. J Am Coll Cardiol 2002; 39: 1258-63 17. Valls-Bertault V, Fatemi M, Gilard M, Pennec PY, Etienne Y, Blanc JJ. Assessment of upgrading to biventricular pacing in patients with right ventricular pacing and congestive heart failure after atrioventricular junctional ablation for chronic atrial fibrillation. Europace 2004; 6: 438-43 18. Frohlich G, Steffel J, Hurlimann D, Enseleit F, Luscher T, Ruschitzka F, Abraham W, Holzmeister J. Upgrading to resynchronization therapy after chronic right ventricular pacing improves left ventricular remodelling. Eur Heart J 2010; 31: 1477–1485 An article from the e-journal of the ESC Council for Cardiology Practice The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

 27/11/2011   High Serum Testosterone Is Associated With Reduced Risk of Cardiovascular Events   High Serum Testosterone Is Associated With Reduced Risk of Cardiovascular Events in Elderly Men The MrOS (Osteoporotic Fractures in Men) Study in Sweden Objectives We tested the hypothesis that serum total testosterone and sex hormone–binding globulin (SHBG) levels predict cardiovascular (CV) events in community-dwelling elderly men. Background Low serum testosterone is associated with increased adiposity, an adverse metabolic risk profile, and athero- sclerosis. However, few prospective studies have demonstrated a protective link between endogenous testoster- one and CV events. Polymorphisms in the SHBG gene are associated with risk of type 2 diabetes, but few stud- ies have addressed SHBG as a predictor of CV events. Methods We used gas chromatography/mass spectrometry to analyze baseline levels of testosterone in the prospective population-based MrOS (Osteoporotic Fractures in Men) Sweden study (2,416 men, age 69 to 81 years). SHBG was measured by immunoradiometric assay. CV clinical outcomes were obtained from central Swedish registers. Results During a median 5-year follow-up, 485 CV events occurred. Both total testosterone and SHBG levels were in- versely associated with the risk of CV events (trend over quartiles: p ! 0.009 and p ! 0.012, respectively). Men in the highest quartile of testosterone (!550 ng/dl) had a lower risk of CV events compared with men in the 3 lower quartiles (hazard ratio: 0.70, 95% confidence interval: 0.56 to 0.88). This association remained after adjustment for traditional CV risk factors and was not materially changed in analyses excluding men with known CV disease at baseline (hazard ratio: 0.71, 95% confidence interval: 0.53 to 0.95). In models that included both testosterone and SHBG, testosterone but not SHBG predicted CV risk. Conclusions High serum testosterone predicted a reduced 5-year risk of CV events in elderly men. (J Am Coll Cardiol 2011; 58:1674–81) © 2011 by the American College of Cardiology Foundation