Showing papers in "European Heart Journal in 2011"

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)

Abstract: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).

Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies

Abstract: We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. Studies were included if they were prospective, follow-up .3 years, had duration of sleep at baseline, and incident cases of CHD, stroke, or CVD. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effect model. Overall, 15 studies (24 cohort samples) included 474 684 male and female participants (follow-up 6.9-25 years), and 16 067 events (4169 for CHD, 3478 for stroke, and 8420 for total CVD). Sleep duration was assessed by questionnaire and incident cases through certifica- tion and event registers. Short duration of sleep was associated with a greater risk of developing or dying of CHD (RR 1.48, 95% CI 1.22-1.80, P , 0.0001), stroke (1.15, 1.00-1.31, P ¼ 0.047), but not total CVD (1.03, 0.93-1.15, P ¼ 0.52) with no evidence of publication bias (P ¼ 0.95, P ¼ 0.30, and P ¼ 0.46, respectively). Long duration of sleep was also associated with a greater risk of CHD (1.38, 1.15-1.66, P ¼ 0.0005), stroke (1.65, 1.45-1.87, P , 0.0001), and total CVD (1.41, 1.19-1.68, P , 0.0001) with no evidence of publication bias (P ¼ 0.92, P ¼ 0.96, and P ¼ 0.79, respectively).

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).

Abstract: 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 …

ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC).

Abstract: 2D : two-dimensional 3D : three-dimensional ABI : ankle–brachial index ACAS : Asymptomatic Carotid Atherosclerosis Study ACCF : American College of Cardiology Foundation ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ACST : Asymptomatic Carotid Surgery Trial ALI : acute limb ischaemia ASTRAL : Angioplasty and Stenting for Renal Artery Lesions trial BASIL : Bypass versus Angioplasty in Severe Ischaemia of the Leg BOA : Dutch Bypass Oral Anticoagulants or Aspirin CABG : coronary artery bypass grafting CAD : coronary artery disease CAPRIE : Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events CAPTURE : Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events CARP : Coronary Artery Revascularization Prophylaxis CAS : carotid artery stenting CASPAR : Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease CASS : Coronary Artery Surgery Study CAVATAS : CArotid and Vertebral Artery Transluminal Angioplasty Study CEA : carotid endarterectomy CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance CI : confidence interval CLEVER : Claudication: Exercise Versus Endoluminal Revascularization CLI : critical limb ischaemia CORAL : Cardiovascular Outcomes in Renal Atherosclerotic Lesions COURAGE : Clinical Outcomes Utilization Revascularization and Aggressive Drug Evaluation CPG : Committee for Practice Guidelines CREST : Carotid Revascularization Endarterectomy vs. Stenting Trial CT : computed tomography CTA : computed tomography angiography CVD : cardiovascular disease DECREASE-V : Dutch Echocardiographic Cardiac Risk Evaluation DRASTIC : Dutch Renal Artery Stenosis Intervention Cooperative Study DSA : digital subtraction angiography DUS : duplex ultrasound/duplex ultrasonography EACTS : European Association for Cardio-Thoracic Surgery EAS : European Atherosclerosis Society ECST : European Carotid Surgery Trial EPD : embolic protection device ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EUROSCORE : European System for Cardiac Operative Risk Evaluation EVA-3S : Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis EXACT : Emboshield and Xact Post Approval Carotid Stent Trial GALA : General Anaesthesia versus Local Anaesthesia for Carotid Surgery GFR : glomerular filtration rate GRACE : Global Registry of Acute Coronary Events HbA1c : glycated haemoglobin HDL : high-density lipoprotein HOPE : Heart Outcomes Prevention Evaluation HR : hazard ratio IC : intermittent claudication ICSS : International Carotid Stenting Study IMT : intima–media thickness ITT : intention to treat LDL : low-density lipoprotein LEAD : lower extremity artery disease MACCEs : major adverse cardiac and cerebrovascular events MDCT : multidetector computed tomography MONICA : Monitoring of Trends and Determinants in Cardiovascular Disease MRA : magnetic resonance angiography MRI : magnetic resonance imaging NASCET : North American Symptomatic Carotid Endarterectomy Trial ONTARGET : Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial OR : odds ratio PAD : peripheral artery diseases PARTNERS : Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival PCI : percutaneous coronary intervention PET : positron emission tomography PRO-CAS : Predictors of Death and Stroke in CAS PTA : percutaneous transluminal angioplasty RAAS : renin–angiotensin–aldosterone system RADAR : Randomized, Multicentre, Prospective Study Comparing Best Medical Treatment Versus Best Medical Treatment Plus Renal Artery Stenting in Patients With Haemodynamically Relevant Atherosclerotic Renal Artery Stenosis RAS : renal artery stenosis RCT : randomized controlled trial REACH : Reduction of Atherothrombosis for Continued Health RR : risk ratio SAPPHIRE : Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy SCAI : Society for Cardiovascular Angiography and Interventions SIR : Society of Interventional Radiology SPACE : Stent-Protected Angioplasty versus Carotid Endarterectomy SPARCL : Stroke Prevention by Aggressive Reduction in Cholesterol Levels Study STAR : Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function SSYLVIA : Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries SVMB : Society for Vascular Medicine and Biology TASC : TransAtlantic Inter-Society Consensus TIA : transient ischaemic attack UEAD : upper extremity artery disease VA : vertebral artery 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 ESC Core Curriculum topics. Guidelines and recommendations should help the physicians to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible physician(s). A large number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for diagnosis, management, and/or prevention of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . …

Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003–06

Abstract: Prolonged sedentary time is ubiquitous in developed economies and is associated with an adverse cardio-metabolic risk profile and premature mortality. This study examined the associations of objectively assessed sedentary time and breaks (interruptions) in sedentary time with continuous cardio-metabolic and inflammatory risk biomarkers, and whether these associations varied by sex, age, and/or race/ethnicity. Methods and results Cross-sectional analyses with 4757 participants (≥20 years) from the 2003/04 and 2005/06 US National Health and Nutrition Examination Survey (NHANES). An Actigraph accelerometer was used to derive sedentary time (,100 counts per minute (cpm)) and breaks in sedentary time. Independent of potential confounders, including moder- ate-to-vigorous exercise, detrimental linear associations (P for trends ,0.05) of sedentary time with waist circum- ference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, HOMA-%B, and HOMA-%S were observed. Independent of potential confounders and sedentary time, breaks were beneficially associated with waist circumfer- ence and C-reactive protein (P for trends ,0.05). There was limited evidence of meaningful differences in associ- ations with biomarkers by age, sex, or race/ethnicity. Notable exceptions were sex-differences in the associations of sedentary time and breaks with HDL-cholesterol, and race/ethnicity differences in the association of sedentary time with waist circumference with associations detrimental in non-Hispanic whites, null in Mexican Americans, and beneficial in non-Hispanic blacks. Conclusion These are the first population-representative findings on the deleterious associations of prolonged sedentary time with cardio-metabolic and inflammatory biomarkers. The findings suggest that clinical communications and preventive health messages on reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk.

Standardized Endpoint Definitions for Transcatheter Aortic Valve Implantation Clinical Trials : A Consensus Report From the Valve Academic Research Consortium

Abstract: Objectives To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health. Background Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

Abstract: Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment

Abstract: Half of patients with heart failure (HF) have a preserved left ventricular ejection fraction (HFpEF). Morbidity and mortality in HFpEF are similar to values observed in patients with HF and reduced EF, yet no effective treatment has been identified. While early research focused on the importance of diastolic dysfunction in the pathophysiology of HFpEF, recent studies have revealed that multiple non-diastolic abnormalities in cardiovascular function also contribute. Diagnosis of HFpEF is frequently challenging and relies upon careful clinical evaluation, echo-Doppler cardiography, and invasive haemodynamic assessment. In this review, the principal mechanisms, diagnostic approaches, and clinical trials are reviewed, along with a discussion of novel treatment strategies that are currently under investigation or hold promise for the future.

The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis

Abstract: Aims A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). Methods and results We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Conclusion Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Transcatheter aortic valve implantation: first results from a multi-centre real-world registry

Abstract: Aims Treatment of elderly symptomatic patients with severe aortic stenosis and co-morbidities is challenging. Transcatheter aortic valve interventions [balloon valvuloplasty and transcatheter aortic valve implantation (TAVI)] are evolving as alternative treatment options to surgical valve replacement. We report the first results of the prospective multi-centre German Transcatheter Aortic Valve Interventions— Registry. Methods and results Between January 2009 and December 2009, a total of 697 patients (81.4 ± 6.3 years, 44.2% males, and logistic EuroScore 20.5 ± 13.2%) underwent TAVI. Pre-operative aortic valve area was 0.6 ± 0.2 cm² with a mean transvalvular gradient of 48.7 ± 17.2 mmHg. Transcatheter aortic valve implantation was performed percutaneously in the majority of patients [666 (95.6%)]. Only 31 (4.4%) procedures were done surgically: 26 (3.7%) transapically and 5 (0.7%) transaortically. The Medtronic CoreValveTM prosthesis was used in 84.4%, whereas the Sapien EdwardsTM prosthesis was used in the remaining cases. Technical success was achieved in 98.4% with a post-operative mean transaortic pressure gradient of 5.4 ± 6.2 mmHg. Any residual aortic regurgitation was observed in 72.4% of patients, with a significant aortic insufficiency (≥Grade III) in only 16 patients (2.3%). Complications included pericardial tamponade in 1.8% and stroke in 2.8% of patients. Permanent pacemaker implantation after TAVI became necessary in 39.3% of patients. In-hospital death rate was 8.2%, and the 30-day death rate 12.4%. Conclusion In this real-world registry of high-risk patients with aortic stenosis, TAVI had a high success rate and was associated with moderate in-hospital complications. However, careful patient selection and continued hospital selection seem crucial to maintain these results.

Corrigendum to: ‘Guidelines for the management of atrial fibrillation’ [European Heart Journal (2010) 31, 2369–2429 and EP-Europace (2010) 12, 1360–1420]

Abstract: The European Society of Cardiology and the publishers regret that a table containing errors was published in these guidelines. Table 15 (page 2399 in …

Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment

Abstract: Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages. Methods and results We randomized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day (15 mg/day if creatinine clearance (CrCl) 30-49 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). Com- pared with patients with CrCl .50 mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/ min were older (79 years) and had higher event rates irrespective of study treatment. Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin (hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.57-1.23) in the per-protocol population. Intention-to-treat analysis yielded similar results (HR 0.86; 95% CI 0.63-1.17) to the per-protocol results. Rates of the principal safety endpoint (major and clinically relevant non-major bleeding: 17.82 vs. 18.28 per 100 patient-years; P ¼ 0.76) and intracranial bleeding (0.71 vs. 0.88 per 100 patient-years; P ¼ 0.54) were similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100 patient-years; P ¼ 0.047) occurred less often with rivaroxaban.

Transcatheter aortic valve implantation: early results of the FRANCE (FRench Aortic National CoreValve and Edwards) registry.

Abstract: AIMS: Transcatheter aortic valve implantation is a therapeutic alternative for high-surgical-risk patients with severe symptomatic aortic stenosis. Two models of prosthesis are currently commercialized in France, which can be implanted either via a transarterial or a transapical approach. The aim of the study was to evaluate in a national French registry the early safety and efficacy of transcatheter aortic valve replacement (AVR) using either the Edwards SAPIEN™ or CoreValve™ in high-surgical-risk patients with severe aortic stenosis. METHODS AND RESULTS: The multicentre national registry was conducted in 16 centres between February 2009 and June 2009, under the authority of the French Societies of Cardiology and Thoracic and Cardio-Vascular Surgery. The primary endpoint was mortality at 1 month. Two hundred and forty-four high-surgical-risk patients (logistic EuroSCORE ≥20%, STS ≥10%, or contra-indication to AVR) were enrolled. Mean age was 82 ± 7 years and 43.9% were female. Edwards SAPIEN and CoreValve were implanted in 68 and 32% of patients, respectively. The approaches used were transarterial (transfemoral: 66%; subclavian: 5%) or transapical in 29%. Device success rate was 98.3% and 30-day mortality was 12.7%. Severe complications included stroke (3.6%), tamponade (2%), acute coronary occlusion (1.2%), and vascular complications (7.3%). Pacemaker was required in 11.8%. At 1 month, 88% of patients were in NYHA class II or less. CONCLUSION: This prospective registry reflects the real-life experience of transcatheter aortic valve implantation in high-risk elderly patients in France. The early results are satisfactory in terms of feasibility, short-term haemodynamic and functional improvement, and safety. Longer term follow-up will be further assessed.

Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial

Abstract: Aims Long-term randomized comparisons of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in left main coronary (LM) disease and/or three-vessel disease (3VD) patients have been limited. This analysis compares 3-year outcomes in LM and/or 3VD patients treated with CABG or PCI with TAXUS Express stents. Methods and results SYNTAX is an 85-centre randomized clinical trial ( n = 1800). Prospectively screened, consecutive LM and/or 3VD patients were randomized if amenable to equivalent revascularization using either technique; if not, they were entered into a registry. Patients in the randomized cohort will continue to be followed for 5 years. At 3 years, major adverse cardiac and cerebrovascular events [MACCE: death, stroke, myocardial infarction (MI), and repeat revascularization; CABG 20.2% vs. PCI 28.0%, P < 0.001], repeat revascularization (10.7 vs. 19.7%, P < 0.001), and MI (3.6 vs. 7.1%, P = 0.002) were elevated in the PCI arm. Rates of the composite safety endpoint (death/stroke/MI 12.0 vs. 14.1%, P = 0.21) and stroke alone (3.4 vs. 2.0%, P = 0.07) were not significantly different between treatment groups. Major adverse cardiac and cerebrovascular event rates were not significantly different between arms in the LM subgroup (22.3 vs. 26.8%, P = 0.20) but were higher with PCI in the 3VD subgroup (18.8 vs. 28.8%, P < 0.001). Conclusions At 3 years, MACCE was significantly higher in PCI- compared with CABG-treated patients. In patients with less complex disease (low SYNTAX scores for 3VD or low/intermediate terciles for LM patients), PCI is an acceptable revascularization, although longer follow-up is needed to evaluate these two revascularization strategies.

Troponin elevation in coronary vs. non-coronary disease

Abstract: Acute myocardial infarction is defined as myocardial cell death due to prolonged myocardial ischaemia. Cardiac troponins (cTn) are the most sensitive and specific biochemical markers of myocardial injury and with the new high-sensitivity troponin methods very minor damages on the heart muscle can be detected. However, elevated cTn levels indicate cardiac injury, but do not define the cause of the injury. Thus, cTn elevations are common in many disease states and do not necessarily indicate the presence of a thrombotic acute coronary syndrome (ACS). In the clinical work it may be difficult to interpret dynamic changes of troponin in conditions such as stroke, pulmonary embolism, sepsis, acute perimyocarditis, Tako-tsubo, acute heart failure, and tachycardia. There are no guidelines to treat patients with elevated cTn levels and no coronary disease. The current strategy of treatment of patients with elevated troponin and non-acute coronary syndrome involves treating the underlying causes. The aim of this paper is to review data from studies of non-ACS patients with acutely elevated troponin who in clinical practice may be difficult to discriminate from ACS patients.

Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial

Abstract: Aim After an acute coronary syndrome, patients remain at risk of recurrent ischaemic events, despite contemporary treatment, including aspirin and clopidogrel. We evaluated the safety and indicators of efficacy of the novel oral direct thrombin inhibitor dabigatran. Methods and results In this double-blind, placebo-controlled, dose-escalation trial, 1861 patients (99.2% on dual antiplatelet treatment) in 161 centres were enrolled at mean 7.5 days (SD 3.8) after an ST-elevation (60%) or non-ST-elevation (40%) myocardial infarction and randomized to twice daily treatment with dabigatran 50 mg ( n = 369), 75 mg ( n = 368), 110 mg ( n = 406), 150 mg ( n = 347), or placebo ( n = 371). Primary outcome was the composite of major or clinically relevant minor bleeding during the 6-month treatment period. There were 96 primary outcome events and, compared with placebo, a dose-dependent increase with dabigatran, hazard ratio (HR) 1.77 (95% confidence intervals 0.70, 4.50) for 50 mg; HR 2.17 (0.88, 5.31) for 75 mg; HR 3.92 (1.72, 8.95) for 110 mg; and HR 4.27 (1.86, 9.81) for 150 mg. Compared with placebo, D-dimer concentrations were reduced in all dabigatran dose groups by an average of 37 and 45% at weeks 1 and 4, respectively ( P < 0.001). Fourteen (3.8%) patients died, had a myocardial infarction or stroke in the placebo group compared with 17 (4.6%) in 50 mg, 18 (4.9%) in 75 mg, 12 (3.0%) in 110 mg, and 12 (3.5%) in the 150 mg dabigatran groups. Conclusions Dabigatran, in addition to dual antiplatelet therapy, was associated with a dose-dependent increase in bleeding events and significantly reduced coagulation activity in patients with a recent myocardial infarction.

Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure

Abstract: Aims In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. Methods and results This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II–IV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2–4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements ( P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes ( P = 0.02). These improvements were maintained at 1 year. Conclusions This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.

Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy.

Abstract: Aims Although pre-revascularization ischaemia testing is recommended, the interaction between the extent of ischaemia and myocardial scar with performance of revascularization on patient survival is unclear. Methods and results We identified 13 969 patients who underwent adenosine or exercise stress SPECT myocardial perfusion scintigraphy (MPS). The percent myocardium ischaemic (%I) and fixed (%F) were calculated using 5 point/20-segment MPS scoring. Patients lost to follow-up (2.8%) were excluded leaving 13 555 patients [35% with history (Hx) of known coronary artery disease (CAD), 65% exercise stress, 61% male, age 66 ± 12]. Follow-up was performed at 12–18 months for early revascularization and at >7 years for all-cause death (ACD) (mean follow-up 8.7 ± 3.3 years). All-cause death was modelled using Cox proportional hazards modelling adjusting for logistic-based propensity scores, MPS, revascularization, and baseline characteristics. During FU, 3893 ACD (29%, 3.3%/year) and 1226 early revascularizations (9.0%) occurred. After risk-adjustment, a three-way interaction was present between %I, early revascularization, and HxCAD, such that %I identified a survival benefit with early revascularization in patients without prior myocardial infarction (MI), whereas no such benefit was present in patients with prior MI (overall model χ2= 3932, P 10% total myocardium, %I identified a survival benefit in all patients. Conclusion In this large observational series with long-term follow-up, patients with significant ischaemia and without extensive scar were likely to realize a survival benefit from early revascularization. In contrast, the survival of patients with minimal ischaemia was superior with medical therapy without early revascularization.

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension.

Abstract: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥50% ste- nosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was deter- mined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an over- estimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence.

One year follow-up of the multi-centre European PARTNER transcatheter heart valve study

Abstract: BackgroundTranscatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option in high-risk patients with severe aortic stenosis.AimsPARTNER EU is the first study to evaluate prospectively the procedural and mid-term outcomes of transfemoral (TF) or transapical (TA) implantation of the Edwards SAPIEN® valve involving a multi-disciplinary approach.Methods and resultsPrimary safety endpoints were 30 days and 6 months mortality. Primary efficacy endpoints were haemodynamic and functional improvement at 12 months. One hundred and thirty patients (61 TF, 69 TA), aged 82.1 ± 5.5 years were included. TA patients had higher logistic EuroSCORE (33.8 vs. 25.7, P <0.0005) and more peripheral disease (49.3 vs. 16.4, P< 0.0001). Procedures were aborted in four TA (5.8) and six TF cases (9.8). Valve implantation was successful in the remaining patients in 95.4 and 96.4, respectively. Thirty days and 6 months survival were 81.2 and 58.0 (TA) and 91.8 and 90.2 (TF). In both groups, mean aortic gradient decreased from 46.9 ± 18.1 to 10.9 ± 5.4 mmHg 6 months post-TAVI. In total, 78.1 and 84.8 of patients experienced significant improvement in New York Heart Association (NYHA) class, whereas 73.9 and 72.7 had improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores in TA and TF cohorts, respectively.ConclusionThis first team-based multi-centre European TAVI registry shows promising results in high-risk patients treated by TF or TA delivery. Survival rates differ significantly between TF and TA groups and probably reflect the higher risk profile of the TA cohort. Optimal patient screening, approach selection, and device refinement may improve outcomes.

Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study.

Abstract: [Eur Heart J 2011;32:1900–1908, doi: 10.1093/eurheartj/ehr077]. Regrettably, on p. 1907, line …

Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity?

Abstract: Non-compaction of the left ventricular myocardium (LVNC) has gained increasing recognition during the last 25 years. There is a morphological trait of the myocardial structure with a spectrum from normal variants to the pathological phenotype of LVNC, which reflects the embryogenic structure of the human heart due to an arrest in the compaction process during the first trimester. It must be cautioned not to overdiagnose LVNC: the morphological spectrum of trabeculations, from normal variants to pathological trabeculations with the morphological feature of LVNC must be carefully considered. The classical triad of complications are heart failure, arrhythmias, including sudden cardiac death, and systemic embolic events. Non-compaction of the left ventricular myocardium can occur in isolation or in association with congenital heart defects (CHDs), genetic syndromes, and neuromuscular disorders among others. The clinical spectrum is wide and the outcome is more favourable than in previously described populations with a negative selection bias. Familial occurrence is frequent with autosomal dominant and X-linked transmissions. Different mutations in sarcomere protein genes were identified and there seems to be a shared molecular aetiology of different cardiomyopathic phenotypes, including LVNC, hypertrophic and dilated cardiomyopathies. Thus, genetic heterogeneity, with an overlap of different phenotypes, and the variability of hereditary patterns, raise the questions whether there is a morphological trait from dilated/hypertrophic cardiomyopathy to LVNC and what are the triggers and modifiers to develop either dilated, hypertrophic cardiomyopathy, or LVNC in patients with the same mutation. The variety in clinical presentation, the genetic heterogeneity, and the phenotype of the first transgenetic animal model of an LVNC-associated mutation question the hypothesis that LVNC be a distinct cardiomyopathy: it seems to be rather a distinct phenotype or phenotypic, morphological expression of different underlying diseases than a distinct cardiomyopathy.

Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation

Abstract: Aims Congenital long QT syndromes (LQTSs) are associated with prolonged ventricular repolarization and sudden cardiac death. Limitations to existing clinical therapeutic management strategies prompted us to develop a novel human in vitro drug-evaluation system for LQTS type 2 (LQT2) that will complement the existing in vitro and in vivo models. Methods and results Skin fibroblasts from a patient with a KCNH2 G1681A mutation (encodes I Kr potassium ion channel) were reprogrammed to human induced pluripotent stem cells (hiPSCs), which were subsequently differentiated to functional cardiomyocytes. Relative to controls (including the patient's mother), multi-electrode array and patch-clamp electrophysiology of LQT2–hiPSC cardiomyocytes showed prolonged field/action potential duration. When LQT2–hiPSC cardiomyocytes were exposed to E4031 (an IKr blocker), arrhythmias developed and these presented as early after depolarizations (EADs) in the action potentials. In contrast to control cardiomyocytes, LQT2–hiPSC cardiomyocytes also developed EADs when challenged with the clinically used stressor, isoprenaline. This effect was reversed by β-blockers, propranolol, and nadolol, the latter being used for the patient's therapy. Treatment of cardiomyocytes with experimental potassium channel enhancers, nicorandil and PD118057, caused action potential shortening and in some cases could abolish EADs. Notably, combined treatment with isoprenaline (enhancers/isoprenaline) caused EADs, but this effect was reversed by nadolol. Conclusions Findings from this paper demonstrate that patient LQT2–hiPSC cardiomyocytes respond appropriately to clinically relevant pharmacology and will be a valuable human in vitro model for testing experimental drug combinations.

Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial

Abstract: Aims To evaluate efficacy and safety of RLY5016 (a non-absorbed, orally administered, potassium [K+]-binding polymer) on serum K+ levels in patients with chronic heart failure (HF) receiving standard therapy and spironolactone. Methods and results One hundred and five patients with HF and a history of hyperkalaemia resulting in discontinuation of a renin–angiotensin–aldosterone system inhibitor/blocker and/or beta-adrenergic blocking agent or chronic kidney disease (CKD) with an estimated glomerular filtration rate of 5.5 mEq/L); and the proportion titrated to spironolactone 50 mg/day. Safety assessments included adverse events (AEs) and clinical laboratory tests. RLY5016 ( n = 55) and placebo ( n = 49) patients had similar baseline characteristics. At the end of treatment, compared with placebo, RLY5016 had significantly lowered serum K+ levels with a difference between groups of −0.45 mEq/L ( P < 0.001); a lower incidence of hyperkalaemia (7.3% RLY5016 vs. 24.5% placebo, P = 0.015); and a higher proportion of patients on spironolactone 50 mg/day (91% RLY5016 vs. 74% placebo, P = 0.019). In patients with CKD ( n = 66), the difference in K+ between groups was −0.52 mEq/L ( P = 0.031), and the incidence of hyperkalaemia was 6.7% RLY5016 vs. 38.5% placebo ( P = 0.041). Adverse events were mainly gastrointestinal, and mild or moderate in severity. Adverse events resulting in study withdrawal were similar (7% RLY5016, 6% placebo). There were no drug-related serious AEs. Hypokalaemia (K+ <3.5 mEq/L) occurred in 6% of RLY5016 patients vs. 0% of placebo patients ( P = 0.094). Conclusion RLY5016 prevented hyperkalaemia and was relatively well tolerated in patients with HF receiving standard therapy and spironolactone (25–50 mg/day) (ClinicalTrials.gov registry identifier: [NCT00868439][1]). [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00868439&atom=%2Fehj%2Fearly%2F2011%2F01%2F05%2Feurheartj.ehq502.atom

Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology.

Abstract: Bleeding has recently emerged as an important outcome in the management of acute coronary syndromes (ACS), which is relatively frequent compared with ischaemic outcomes and has important implications in terms of prognosis, outcomes, and costs. In particular, there is evidence that patients experiencing major bleeding in the acute phase are at higher risk for death in the following months, although the causal nature of this relation is still debated. This position paper aims to summarize current knowledge regarding the epidemiology of bleeding in ACS and percutaneous coronary intervention, including measurement and definitions of bleeding, with emphasis on the recent consensus Bleeding Academic Research Consortium (BARC) definitions. It also provides an European perspective on management strategies to minimize the rate, extent, and consequences of bleeding. Finally, the research implications of bleeding (measuring and reporting bleeding in trials, the importance of bleeding as an outcome measure, and bleeding as a subject for future research) are also discussed.

Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial.

Abstract: AimsMore intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors o ...

An overview of the objectives of and the approaches to propensity score analyses

Abstract: The assessment of treatment effects from observational studies may be biased with patients not randomly allocated to the experimental or control group. One way to overcome this conceptual shortcoming in the design of such studies is the use of propensity scores to adjust for differences of the characteristics between patients treated with experimental and control interventions. The propensity score is defined as the probability that a patient received the experimental intervention conditional on pre-treatment characteristics at baseline. Here, we review how propensity scores are estimated and how they can help in adjusting the treatment effect for baseline imbalances. We further discuss how to evaluate adequate overlap of baseline characteristics between patient groups, provide guidelines for variable selection and model building in modelling the propensity score, and review different methods of propensity score adjustments. We conclude that propensity analyses may help in evaluating the comparability of patients in observational studies, and may account for more potential confounding factors than conventional covariate adjustment approaches. However, bias due to unmeasured confounding cannot be corrected for.

Corrigendum to: ‘Guidelines for the diagnosis and treatment of pulmonary hypertension’ [European Heart Journal (2009) 30, 2493–2537]. The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT)

Abstract: The 2009 ESC Practice Clinical Guidelines for the diagnosis and treatment of pulmonary hypertension included the endothelin receptor antagonist sitaxentan in an algorithm of evidence-based treatment for pulmonary arterial hypertension. Sitaxentan was recommended with a Class I/Level A grade of evidence in WHO functional class III patients and Class IIa/Level C grade of evidence in WHO functional clsses II and IV. Sitaxentan was initially authorized by …

Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients.

Abstract: Aims Infection is a serious complication of pacemaker (PM) systems. Although the rate of infection has been debated, the figures are largely unknown. We therefore studied the incidence of PM infection and its associated risk factors in the Danish population. Methods and results Since 1982, all PM implantation and removal procedures performed in Denmark have been prospectively recorded in the Danish Pacemaker Register. All patients ( n = 46299) who underwent implantation between 1982 and 2007 were included. The total length of surveillance was 236 888 PM-years. The incidence of infection was calculated according to the total number of PM-years. The incidence of surgical site infection (≤365 days after PM implantation) was compared with later infection in first implant and replacement procedures. Multiple-record and multiple-event-per-subject proportional hazards analyses were used to identify the independent risk factors of PM infection. Surgical site infection occurred in 192 cases after first implantation (incidence rate 4.82/1000 PM-years), and in 133 cases after replacement (12.12/1000 PM-years). Infections occurring more than 365 days after the first implantation occurred in 153 cases (1.02/1000 PM-years), and in 118 cases after replacement (3.26/1000 PM-years). Independent factors associated with an increased risk of PM infection were a greater number of PM operations (including replacements), male sex, younger age, implantation during the earliest part of the study period, and absence of antibiotics ( P < 0.001). Conclusion The overall risk of infection after PM implantation was low. A greater number of operations augmented the risk of infection. This should be taken into account when considering revisions of PM systems.