Pre-participation screenings frequently miss occult cardiovascular conditions in apparently healthy male middle-aged first-time marathon runners

INTRODUCTION: The optimal pre-participation screening strategy to identify athletes at risk for exercise-induced cardiovascular events is unknown. We therefore aimed to compare the American College of Sports Medicine (ACSM) and European Society of Cardiology (ESC) pre-participation screening strategies against extensive cardiovascular evaluations in identifying high-risk individuals among 35-50-year-old apparently healthy men. METHODS: We applied ACSM and ESC pre-participation screenings to 25 men participating in a study on first-time marathon running. We compared screening outcomes against medical history, physical examination, electrocardiography, blood tests, echocardiography, cardiopulmonary exercise testing, and magnetic resonance imaging. RESULTS: ACSM screening classified all participants as 'medical clearance not necessary'. ESC screening classified two participants as 'high-risk'. Extensive cardiovascular evaluations revealed ≥1 minor abnormality and/or cardiovascular condition in 17 participants, including three subjects with mitral regurgitation and one with a small atrial septal defect. Eleven participants had dyslipidaemia, six had hypertension, and two had premature atherosclerosis. Ultimately, three (12%) subjects had a serious cardiovascular condition warranting sports restrictions: aortic aneurysm, hypertrophic cardiomyopathy (HCM), and myocardial fibrosis post-myocarditis. Of these three participants, only one had been identified as 'high-risk' by the ESC screening (for dyslipidaemia, not HCM) and none by the ACSM screening. CONCLUSION: Numerous occult cardiovascular conditions are missed when applying current ACSM/ESC screening strategies to apparently healthy middle-aged men engaging in their first high-intensity endurance sports event

Subcutaneous or Transvenous Defibrillator Therapy.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) was designed to avoid complications related to the transvenous ICD lead by using an entirely extrathoracic placement. Evidence comparing these systems has been based primarily on observational studies. METHODS: We conducted a noninferiority trial in which patients with an indication for an ICD but no indication for pacing were assigned to receive a subcutaneous ICD or transvenous ICD. The primary end point was the composite of device-related complications and inappropriate shocks; the noninferiority margin for the upper boundary of the 95% confidence interval for the hazard ratio (subcutaneous ICD vs. transvenous ICD) was 1.45. A superiority analysis was prespecified if noninferiority was established. Secondary end points included death and appropriate shocks. RESULTS: A total of 849 patients (426 in the subcutaneous ICD group and 423 in the transvenous ICD group) were included in the analyses. At a median follow-up of 49.1 months, a primary end-point event occurred in 68 patients in the subcutaneous ICD group and in 68 patients in the transvenous ICD group (48-month Kaplan-Meier estimated cumulative incidence, 15.1% and 15.7%, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.71 to 1.39; P = 0.01 for noninferiority; P = 0.95 for superiority). Device-related complications occurred in 31 patients in the subcutaneous ICD group and in 44 in the transvenous ICD group (hazard ratio, 0.69; 95% CI, 0.44 to 1.09); inappropriate shocks occurred in 41 and 29 patients, respectively (hazard ratio, 1.43; 95% CI, 0.89 to 2.30). Death occurred in 83 patients in the subcutaneous ICD group and in 68 in the transvenous ICD group (hazard ratio, 1.23; 95% CI, 0.89 to 1.70); appropriate shocks occurred in 83 and 57 patients, respectively (hazard ratio, 1.52; 95% CI, 1.08 to 2.12). CONCLUSIONS: In patients with an indication for an ICD but no indication for pacing, the subcutaneous ICD was noninferior to the transvenous ICD with respect to device-related complications and inappropriate shocks. (Funded by Boston Scientific; PRAETORIAN ClinicalTrials.gov number, NCT01296022.)

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Accelerated Idioventricular Rhythm in a Young Athlete: Physiology or Pathology?

An accelerated idioventricular rhythm was seen on a routine preparticipation electrocardiogram of a 19-year-old healthy and symptom-free athlete. Family history was negative for cardiac disease. Additional investigations revealed a hypertrophic cardiomyopathy, confirmed with cardiac magnetic resonance imaging and genetic analysis. Accelerated idioventricular rhythm in young athletes warrants careful clinical evaluation. (Level of Difficulty: Advanced.

Recombinant factor VIIa reverses the anticoagulant effect of the long-acting pentasaccharide idraparinux in healthy volunteers

We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo-controlled trial, comparing idraparinux [7.5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 mug/kg intravenous (i.v.)] (n=6), or idraparinux (7.5 mg s.c) followed after 1 week by rFVIIa (90 mug/kg i.v.)(n=6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F1+2) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre-idraparinux values. A clear increase of F1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux-inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patient

Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty

OBJECTIVES We investigated the safety and pharmacodynamics of escalating doses of recombinant nematode anticoagulant protein c2 (rNAPc2) in patients undergoing elective coronary angioplasty. BACKGROUND Recombinant NAPc2 is a potent inhibitor of the tissue factor/factor VIIa complex, which has the potential to reduce the risk of thrombotic complications in coronary artery disease. METHODS In a randomized, double-blinded, dose-escalation, multicenter trial, 154 patients received placebo or rNAPc2 at doses of 3.5, 5.0, 7.5, and 10.0 mug/kg body weight as a single subcutaneous administration 2 to 6 h before angioplasty. All patients received aspirin, unfractionated heparin during angioplasty, and clopidogrel in case of stent implantation. RESULTS Minor bleeding rates for the doses 3.5 to 7.5 mug/kg were comparable to that with placebo (6.7%), whereas an incidence of 26.9% was observed at the 10.0-mug/kg dose level (p <0.01). Major bleedings occurred in the 5.0-mug/kg (n = 3) and 7.5-mug/kg (n = 1) dose groups. The three patients in the 5.0-mug/kg dose group also received a glycoprotein IIb/IIIa receptor inhibitor at the moment of major bleeding. Systemic thrombin generation, as measured by prothrombin fragment 1+2 (F1+2), was suppressed in all rNAPc2 dose groups to levels below pretreatment values for at least 36 h. In the placebo group, a distinct increase of F1+2 levels was observed following cessation of heparin. CONCLUSIONS Inhibition of the tissue factor/factor VIIa complex with rNAPc2, at doses up to 7.5 mug/kg, in combination with aspirin, clopidogrel, and unfractionated heparin appears to be a safe and effective strategy to prevent thrombin generation during coronary angioplasty. (J Am Coll Cardiol 2003;41:2147-53) (C) 2003 by the American College of Cardiology Foundatio

Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers

Background-The novel anticoagulant fondaparinux proved to be effective and safe in the postoperative prevention of venous thrombosis. Current phase III trials with this synthetic selective factor Xa inhibitor focus on its use in the treatment of patients with venous and arterial thrombosis. As with any anticoagulant therapy, there is a risk of bleeding complications; hence, a strategy to reverse the effects of fondaparinux is desirable. The aim of this study was to investigate whether recombinant factor VIIa (rFVIIa) could neutralize the anticoagulant effects of subcutaneously administered fondaparinux. Methods and Results-In a randomized, placebo-controlled design, 16 healthy male subjects received either a single subcutaneous dose of fondaparinux (10 mg) and a single intravenous bolus of rFVIIa (90 mug/kg; n=8), fondaparinux and placebo (n=4), or placebo and rFVIIa (n=4). Fondaparinux (or placebo) was administered 2 hours before rFVIIa (or placebo). Injection of rFVIIa after fondaparinux normalized the prolonged activated partial thromboplastin and prothrombin times and reversed the decrease in prothrombin activation fragments 1+2 (F1+2), as observed with fondaparinux alone. Thrombin-generation time and endogenous thrombin potential, which were inhibited by fondaparinux, normalized up to 6 hours after rFVIIa injection. Conclusions-rFVIIa is capable of normalizing coagulation times and thrombin generation during fondaparinux treatment. The duration of this effect ranged from 2 to 6 hours after rFVIIa injection. These results suggest that rFVIIa may be useful to reverse the anticoagulant effect of fondaparinux in case of serious bleeding complications or need for acute surgery during treatment with fondaparinu