Showing papers in "European Heart Journal in 2014"

2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC)

Abstract: 2D : two-dimensional 99mTc-DPD : 99mTechnetium-3,3-diphosphono- 1,2-propanodi-carboxylic acid ACE : angiotensin-converting enzyme AF : atrial fibrillation AL : amyloid light chain AR : aortic regurgitation ARB : angiotensin receptor blocker ATTR : amyloidosis-transthyretin type AV : atrioventricular BiVAD : biventricular assist device BNP : brain natriuretic peptide BPM : Beats per minute CCS : Canadian Cardiovascular Society CFC : cardiofacialcutaneous CHA2DS2-VASc : Congestive Heart failure, hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65–74, and Sex (female) CMR : cardiac magnetic resonance CRT : cardiac resynchronization therapy CRT-D : cardiac resynchronization therapy-defibrillator CRT-P : Cardiac resynchronization therapy with a pacemaker CT : computed tomography DC : direct current DNA : deoxyribonucleic acid E/A : ratio of mitral peak velocity of early filling (E) to mitral peak velocity of late filling (A) E/e’ : ratio of early transmitral flow velocity (E) to early mitral annulus velocity (e’) EACTS : European Association for Cardio-Thoracic Surgery ECG : electrocardiogram EF : ejection fraction EPS : electrophysiological study ESC : European Society of Cardiology FDA : (US) Food and Drug Administration FHL1 : four and a half LIM domains 1 HAS-BLED : hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly (>65 years), drugs/alcohol concomitantly HCM : hypertrophic cardiomyopathy hs-cTnT : high sensitivity cardiac troponin T HTS : high throughput sequencing ICD : implantable cardioverter defibrillator ILR : implantable loop recorder INR : international normalized ratio IUD : intrauterine device LA : left atrium LAMP-2 : lysosome-associated membrane protein 2 LBBB : left bundle branch block LEOPARD : Lentigines, ECG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, and sensory-neural Deafness LGE : late gadolinium enhancement LV : left ventricular LVAD : left ventricular assist device LVH : left ventricular hypertrophy LVOTO : left ventricular outlow tract obstruction MADIT-RIT : Multicenter Automatic Defibrillator Implantation Trial—Reduce Inappropriate Therapy MAPK : mitogen activated protein kinase MELAS : mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes MERFF : myoclonic epilepsy with ragged red fibres MRA : mineralocorticoid receptor antagonist MYBPC3 : myosin-binding protein C, cardiac-type MYH7 : myosin-7 (s-myosin heavy chain) MYL3 : myosin light chain 3 NOAC : new oral anticoagulants NSVT : non-sustained ventricular tachycardia NT-proBNP : N-terminal pro brain natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulants o.d. : omni die (every day) PC-CMR : phase contrast cardiac magnetic resonance PDE5 : phosphodiesterase type 5 PET : positron emission tomography PRKAG2 : gamma-2 sub-unit of the adenosine monophosphate-activated protein kinase RAAS : renin angiotensin aldosterone system RV : right ventricular SAM : systolic anterior motion SCD : sudden cardiac death SAA : septal alcohol ablation S-ICD™ : Subcutaneous lead implantable cardioverter defibrillator SPECT : single photon emission computed tomography SSFP : steady-state free precession SVT : supraventricular tachycardia TOE : transoesophageal echocardiography TNNI3 : troponin I, cardiac muscle TNNT2 : troponin T, cardiac muscle TPM1 : tropomyosin alpha-1 chain TTE : transthoracic echocardiography TTR : transthyretin VF : ventricular fibrillation VKA : vitamin K antagonist VT : ventricular tachycardia 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 health professionals 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 and recommendations should help the health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. A great number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organisations. 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 management (including diagnosis, treatment, prevention and rehabilitation) 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 management options were weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . The experts of …

2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

Abstract: This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.

2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism

Abstract: ACS : acute coronary syndrome AMPLIFY : Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-line Therapy aPTT : activated partial thromboplastin time b.i.d. : bis in diem (twice daily) b.p.m. : beats per minute BNP : brain natriuretic peptide BP : blood pressure CI : confidence interval CO : cardiac output COPD : chronic obstructive pulmonary disease CPG : Committee for Practice Guidelines CRNM : clinically relevant non-major CT : computed tomographic/tomogram CTEPH : chronic thromboembolic pulmonary hypertension CUS : compression venous ultrasonography DSA : digital subtraction angiography DVT : deep vein thrombosis ELISA : enzyme-linked immunosorbent assay ESC : European Society of Cardiology H-FABP : heart-type fatty acid-binding protein HIT : heparin-induced thrombocytopenia HR : hazard ratio ICOPER : International Cooperative Pulmonary Embolism Registry ICRP : International Commission on Radiological Protection INR : international normalized ratio iPAH : idiopathic pulmonary arterial hypertension IVC : inferior vena cava LMWH : low molecular weight heparin LV : left ventricle/left ventricular MDCT : multi-detector computed tomographic (angiography) MRA : magnetic resonance angiography NGAL : neutrophil gelatinase-associated lipocalin NOAC(s) : Non-vitamin K-dependent new oral anticoagulant(s) NT-proBNP : N-terminal pro-brain natriuretic peptide o.d. : omni die (every day) OR : odds ratio PAH : pulmonary arterial hypertension PE : pulmonary embolism PEA : pulmonary endarterectomy PEITHO : Pulmonary EmbolIsm THrOmbolysis trial PESI : pulmonary embolism severity index PH : pulmonary hypertension PIOPED : Prospective Investigation On Pulmonary Embolism Diagnosis PVR : pulmonary vascular resistance RIETE : Registro Informatizado de la Enfermedad Thromboembolica venosa RR : relative risk rtPA : recombinant tissue plasminogen activator RV : right ventricle/ventricular SPECT : single photon emission computed tomography sPESI : simplified pulmonary embolism severity index TAPSE : tricuspid annulus plane systolic excursion Tc : technetium TOE : transoesophageal echocardiography TTR : time in therapeutic range TV : tricuspid valve UFH : unfractionated heparin V/Q scan : ventilation–perfusion scintigraphy VKA : vitamin K antagonist(s) VTE : venous thromboembolism Guidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting health professionals 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 and recommendations should help the health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. A great number of Guidelines have …

2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA).

Abstract: AAA : abdominal aortic aneurysm ACEI : angiotensin converting enzyme inhibitor ACS : acute coronary syndromes AF : atrial fibrillation AKI : acute kidney injury AKIN : Acute Kidney Injury Network ARB : angiotensin receptor blocker ASA : American Society of Anesthesiologists b.i.d. : bis in diem (twice daily) BBSA : Beta-Blocker in Spinal Anesthesia BMS : bare-metal stent BNP : B-type natriuretic peptide bpm : beats per minute CABG : coronary artery bypass graft CAD : coronary artery disease CARP : Coronary Artery Revascularization Prophylaxis CAS : carotid artery stenting CASS : Coronary Artery Surgery Study CEA : carotid endarterectomy CHA2DS2-VASc : cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65–74 and sex category (female) CI : confidence interval CI-AKI : contrast-induced acute kidney injury CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease Epidemiology Collaboration Cmax : maximum concentration CMR : cardiovascular magnetic resonance COPD : chronic obstructive pulmonary disease CPG : Committee for Practice Guidelines CPX/CPET : cardiopulmonary exercise test CRP : C-reactive protein CRT : cardiac resynchronization therapy CRT-D : cardiac resynchronization therapy defibrillator CT : computed tomography cTnI : cardiac troponin I cTnT : cardiac troponin T CVD : cardiovascular disease CYP3a4 : cytochrome P3a4 enzyme DAPT : dual anti-platelet therapy DECREASE : Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography DES : drug-eluting stent DIPOM : DIabetic Post-Operative Mortality and Morbidity DSE : dobutamine stress echocardiography ECG : electrocardiography/electrocardiographically/electrocardiogram eGFR : estimated glomerular filtration rate ESA : European Society of Anaesthesiology ESC : European Society of Cardiology EVAR : endovascular abdominal aortic aneurysm repair FEV1 : Forced expiratory volume in 1 second HbA1c : glycosylated haemoglobin HF-PEF : heart failure with preserved left ventricular ejection fraction HF-REF : heart failure with reduced left ventricular ejection fraction ICD : implantable cardioverter defibrillator ICU : intensive care unit IHD : ischaemic heart disease INR : international normalized ratio IOCM : iso-osmolar contrast medium KDIGO : Kidney Disease: Improving Global Outcomes LMWH : low molecular weight heparin LOCM : low-osmolar contrast medium LV : left ventricular LVEF : left ventricular ejection fraction MaVS : Metoprolol after Vascular Surgery MDRD : Modification of Diet in Renal Disease MET : metabolic equivalent MRI : magnetic resonance imaging NHS : National Health Service NOAC : non-vitamin K oral anticoagulant NSQIP : National Surgical Quality Improvement Program NSTE-ACS : non-ST-elevation acute coronary syndromes NT-proBNP : N-terminal pro-BNP O2 : oxygen OHS : obesity hypoventilation syndrome OR : odds ratio P gp : platelet glycoprotein PAC : pulmonary artery catheter PAD : peripheral artery disease PAH : pulmonary artery hypertension PCC : prothrombin complex concentrate PCI : percutaneous coronary intervention POBBLE : Peri-Operative Beta-BLockadE POISE : Peri-Operative ISchemic Evaluation POISE-2 : Peri-Operative ISchemic Evaluation 2 q.d. : quaque die (once daily) RIFLE : Risk, Injury, Failure, Loss, End-stage renal disease SPECT : single photon emission computed tomography SVT : supraventricular tachycardia SYNTAX : Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery TAVI : transcatheter aortic valve implantation TdP : torsades de pointes TIA : transient ischaemic attack TOE : transoesophageal echocardiography TOD : transoesophageal doppler TTE : transthoracic echocardiography UFH : unfractionated heparin VATS : video-assisted thoracic surgery VHD : valvular heart disease VISION : Vascular Events In Noncardiac Surgery Patients Cohort Evaluation VKA : vitamin K antagonist VPB : ventricular premature beat VT : ventricular tachycardia Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting health professionals 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 …

Towards better clinical prediction models: seven steps for development and an ABCD for validation

Abstract: Clinical prediction models provide risk estimates for the presence of disease (diagnosis) or an event in the future course of disease (prognosis) for individual patients. Although publications that present and evaluate such models are becoming more frequent, the methodology is often suboptimal. We propose that seven steps should be considered in developing prediction models: (i) consideration of the research question and initial data inspection; (ii) coding of predictors; (iii) model specification; (iv) model estimation; (v) evaluation of model performance; (vi) internal validation; and (vii) model presentation. The validity of a prediction model is ideally assessed in fully independent data, where we propose four key measures to evaluate model performance: calibration-in-the-large, or the model intercept (A); calibration slope (B); discrimination, with a concordance statistic (C); and clinical usefulness, with decision-curve analysis (D). As an application, we develop and validate prediction models for 30-day mortality in patients with an acute myocardial infarction. This illustrates the usefulness of the proposed framework to strengthen the methodological rigour and quality for prediction models in cardiovascular research.

Depression and cardiovascular disease: a clinical review

Abstract: Cardiovascular disease (CVD) and depression are common. Patients with CVD have more depression than the general population. Persons with depression are more likely to eventually develop CVD and also have a higher mortality rate than the general population. Patients with CVD, who are also depressed, have a worse outcome than those patients who are not depressed. There is a graded relationship: the more severe the depression, the higher the subsequent risk of mortality and other cardiovascular events. It is possible that depression is only a marker for more severe CVD which so far cannot be detected using our currently available investigations. However, given the increased prevalence of depression in patients with CVD, a causal relationship with either CVD causing more depression or depression causing more CVD and a worse prognosis for CVD is probable. There are many possible pathogenetic mechanisms that have been described, which are plausible and that might well be important. However, whether or not there is a causal relationship, depression is the main driver of quality of life and requires prevention, detection, and management in its own right. Depression after an acute cardiac event is commonly an adjustment disorder than can improve spontaneously with comprehensive cardiac management. Additional management strategies for depressed cardiac patients include cardiac rehabilitation and exercise programmes, general support, cognitive behavioural therapy, antidepressant medication, combined approaches, and probably disease management programmes.

A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD)

Abstract: Aims Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) in young adults. Current risk algorithms provide only a crude estimate of risk and fail to account for the different effect size of individual risk factors. The aim of this study was to develop and validate a new SCD risk prediction model that provides individualized risk estimates. Methods and results The prognostic model was derived from a retrospective, multi-centre longitudinal cohort study. The model was developed from the entire data set using the Cox proportional hazards model and internally validated using bootstrapping. The cohort consisted of 3675 consecutive patients from six centres. During a follow-up period of 24 313 patient-years (median 5.7 years), 198 patients (5%) died suddenly or had an appropriate implantable cardioverter defibrillator (ICD) shock. Of eight pre-specified predictors, age, maximal left ventricular wall thickness, left atrial diameter, left ventricular outflow tract gradient, family history of SCD, non-sustained ventricular tachycardia, and unexplained syncope were associated with SCD/appropriate ICD shock at the 15% significance level. These predictors were included in the final model to estimate individual probabilities of SCD at 5 years. The calibration slope was 0.91 (95% CI: 0.74, 1.08), C-index was 0.70 (95% CI: 0.68, 0.72), and D-statistic was 1.07 (95% CI: 0.81, 1.32). For every 16 ICDs implanted in patients with ≥4% 5-year SCD risk, potentially 1 patient will be saved from SCD at 5 years. A second model with the data set split into independent development and validation cohorts had very similar estimates of coefficients and performance when externally validated. Conclusion This is the first validated SCD risk prediction model for patients with HCM and provides accurate individualized estimates for the probability of SCD using readily collected clinical parameters.

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Abstract: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. Methods and results EarlydiagnosisofHoFHandpromptinitiationofdietandlipid-loweringtherapyarecritical.Genetictestingmayprovidea definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend thatpatients with suspected HoFH arepromptly referred to specialistcentres foracomprehensiveACVDevaluationandclinicalmanagement.Lifestyleinterventionandmaximalstatintherapyarethemainstaysof treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying

Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis.

Abstract: Aims Chronic kidney disease (CKD) and worsening renal function (WRF) have been associated with poor outcome in heart failure (HF). Methods and results Articles were identified by literature search of MEDLINE (from inception to 1 July 2012) and Cochrane. We included studies on HF patients and mortality risk with CKD and/or WRF. In a secondary analysis, we selected studies investigating predictors of WRF. We retrieved 57 studies (1 076 104 patients) that investigated CKD and 28 studies (49 890 patients) that investigated WRF. The prevalence of CKD was 32% and associated with all-cause mortality: odds ratio (OR) 2.34, 95% confidence interval (CI) 2.20–2.50, P < 0.001). Worsening renal function was present in 23% and associated with unfavourable outcome (OR 1.81, 95% CI 1.55–2.12, P < 0.001). In multivariate analysis, moderate renal impairment: hazard ratio (HR) 1.59, 95% CI 1.49–1.69, P < 0.001, severe renal impairment, HR 2.17, 95% CI 1.95–2.40, P < 0.001, and WRF, HR 1.95, 95% CI 1.45–2.62, P < 0.001 were all independent predictors of mortality. Across studies, baseline CKD, history of hypertension and diabetes, age, and diuretic use were significant predictors for the occurrence of WRF. Conclusion Across all subgroups of patients with HF, CKD, and WRF are prevalent and associated with a strongly increased mortality risk, especially CKD. Specific conditions may predict the occurrence of WRF and thereby poor prognosis.

Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark.

Abstract: Aims Complications after cardiac implantable electronic device (CIED) treatment, including permanent pacemakers (PMs), cardiac resynchronization therapy devices with defibrillators (CRT-Ds) or without (CRT-Ps), and implantable cardioverter defibrillators (ICDs), are associated with increased patient morbidity, healthcare costs, and possibly increased mortality. Methods and results Population-based cohort study in all Danish patients who underwent a CIED procedure from May 2010 to April 2011. Data on complications were gathered on review of all patient charts while baseline data were obtained from the Danish Pacemaker and ICD Register. Adjusted risk ratios (aRRs) with 95% confidence intervals were estimated using binary regression. The study population consisted of 5918 consecutive patients. A total of 562 patients (9.5%) experienced at least one complication. The risk of any complication was higher if the patient was a female (aRR 1.3; 1.1–1.6), underweight (aRR 1.5; 1.1–2.3), implanted in a centre with an annual volume <750 procedures (0–249 procedures: aRR 1.6; 1.1–2.2, 250–499: aRR 2.0; 1.6–2.7, 500–749: aRR 1.5; 1.2–1.8), received a dual-chamber ICD (aRR 2.0; 1.4–2.7) or CRT-D (aRR 2.6; 1.9–3.4), underwent system upgrade or lead revision (aRR 1.3; 1.0–1.7), had an operator with an annual volume <50 procedures (aRR 1.9; 1.4–2.6), or underwent an emergency, out-of-hours procedure (aRR 1.5; 1.0–2.3). Conclusion CIED complications are more frequent than generally acknowledged. Both patient- and procedure-related predictors may identify patients with a particularly high risk of complications. This information should be taken into account both in individual patient treatment and in the planning of future organization of CIED treatment.

Coronary microvascular dysfunction: an update

Abstract: Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy

Medial vascular calcification revisited: review and perspectives

Abstract: Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area.

Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS)

Abstract: Atrial fibrillation (AF) confers a substantial risk of mortality and morbidity from stroke and thrombo-embolism, and this common cardiac arrhythmia represents a major healthcare burden in Europe.1 Stroke prevention is central to the management of AF patients, with the 2012 focused update of the European Society of Cardiology (ESC) guidelines2 recommending oral anticoagulation (OAC) using well-controlled adjusted dose vitamin K antagonists (VKAs, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, previously referred to as new or novel OACs3) for patients with AF and ≥1 stroke risk factor(s). Also, these guidelines strongly advocate a clinical practice shift so that the initial decision step now is the identification of ‘truly low risk’ patients, essentially those aged <65 years without any stroke risk factor (both male and female), who do not need any antithrombotic therapy.2 The ESC guidelines also recommend the use of the CHA2DS2-VASc score4 for stroke risk assessment, and define ‘low-risk’ patients as those with a CHA2DS2-VASc score = 0 (males) or score = 1 (females). Subsequent to this initial step of identifying the low-risk patients, effective stroke prevention (which is essentially OAC) can then be offered to AF patients with ≥1 stroke risk factor(s), with treatment decisions made in consultation with patients and incorporating their preferences. In everyday clinical practice, over 80% of all patients with AF have an indication for OAC, and vascular disease co-exists in ∼30% of them.5–7 With an estimated prevalence of AF of 1–2% and ∼20% of these requiring percutaneous cardiovascular interventions over time,8 ∼1–2 million AF patients in Europe who are …

Cardiovascular effects of environmental noise exposure

Abstract: The role of noise as an environmental pollutant and its impact on health are being increasingly recognized. Beyond its effects on the auditory system, noise causes annoyance and disturbs sleep, and it impairs cognitive performance. Furthermore, evidence from epidemiologic studies demonstrates that environmental noise is associated with an increased incidence of arterial hypertension, myocardial infarction, and stroke. Both observational and experimental studies indicate that in particular night-time noise can cause disruptions of sleep structure, vegetative arousals (e.g. increases of blood pressure and heart rate) and increases in stress hormone levels and oxidative stress, which in turn may result in endothelial dysfunction and arterial hypertension. This review focuses on the cardiovascular consequences of environmental noise exposure and stresses the importance of noise mitigation strategies for public health.

Central blood pressure: current evidence and clinical importance

Abstract: Pressure measured with a cuff and sphygmomanometer in the brachial artery is accepted as an important predictor of future cardiovascular risk. However, systolic pressure varies throughout the arterial tree, such that aortic (central) systolic pressure is actually lower than corresponding brachial values, although this difference is highly variable between individuals. Emerging evidence now suggests that central pressure is better related to future cardiovascular events than is brachial pressure. Moreover, anti-hypertensive drugs can exert differential effects on brachial and central pressure. Therefore, basing treatment decisions on central, rather than brachial pressure, is likely to have important implications for the future diagnosis and management of hypertension. Such a paradigm shift will, however, require further, direct evidence that selectively targeting central pressure, brings added benefit, over and above that already provided by brachial artery pressure.

Inflammatory Cytokines and Risk of Coronary Heart Disease: New Prospective Study and Updated Meta-Analysis

Abstract: Aims Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta-analysis of prospective studies. Methods and results Interleukin-6 (IL-6), IL-18, matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and tumour necrosis factor-α (TNF-α) were measured at baseline in a case-cohort study of 1514 participants and 833 incident CHD events within population-based prospective cohorts at the Danish Research Centre for Prevention and Health. Age- and sex-adjusted hazard ratios (HRs) for CHD per 1-SD higher log-transformed baseline levels were: 1.37 (95% CI: 1.21–1.54) for IL-6, 1.26 (1.11–1.44) for IL-18, 1.30 (1.16–1.46) for MMP-9, 1.01 (0.89–1.15) for sCD40L, and 1.13 (1.01–1.27) for TNF-α. Multivariable adjustment for conventional vascular risk factors attenuated the HRs to: 1.26 (1.08–1.46) for IL-6, 1.12 (0.95–1.31) for IL-18, 1.21 (1.05–1.39) for MMP-9, 0.93 (0.78–1.11) for sCD40L, and 1.14 (1.00–1.31) for TNF-α. In meta-analysis of up to 29 population-based prospective studies, adjusted relative risks for non-fatal MI or CHD death per 1-SD higher levels were: 1.25 (1.19–1.32) for IL-6; 1.13 (1.05–1.20) for IL-18; 1.07 (0.97–1.19) for MMP-9; 1.07 (0.95–1.21) for sCD40L; and 1.17 (1.09–1.25) for TNF-α. Conclusions Several different pro-inflammatory cytokines are each associated with CHD risk independent of conventional risk factors and in an approximately log-linear manner. The findings lend support to the inflammation hypothesis in vascular disease, but further studies are needed to assess causality.

Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide

Abstract: Aims Recent metabolomics and animal model studies show trimethylamine- N -oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. Methods and results We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4–6.2)μM, 9.8 (7.9–12.2)μM, and 41.1 (32.5–52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline ( r = 0.33, P < 0.001) and less between TMAO and betaine ( r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03–1.74), P < 0.05], and betaine levels [1.33 (1.03–1.73), P < 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Conclusion Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO.

Right heart dysfunction in heart failure with preserved ejection fraction

Abstract: Heart failure and preserved ejection fraction patients (n ¼ 96) and controls (n ¼ 46) underwent right heart catheteriza- tion, echocardiographic assessment, and follow-up. Right and left heart filling pressures, pulmonary artery (PA) pressures, and right-sided chamber dimensions were higher in HFpEF compared with controls, while left ventricular size and EF were similar. Right ventricular dysfunction (defined by RV fractional area change, FAC ,35%) was present in 33% of HFpEF patients and was associated with more severe symptoms and greater comorbidity burden. Right ventricular function was impaired in HFpEF compared with controls using both load-dependent (FAC: 40+ 10 vs. 53+ 7%, P , 0.0001) and load-independent indices (FAC adjusted to PA pressure, P ¼ 0.003), with enhanced afterload-sensitivity compared with controls (steeper FAC vs. PA pressure relationship). In addition to haemodynamic load, RVD in HFpEF was asso- ciated with male sex, atrial fibrillation, coronary disease, and greater ventricular interdependence. Over a median follow-up of 529 days (IQR: 143-1066), 31% of HFpEF patients died. In Cox analysis, RVD was the strongest predictor of death (HR: 2.4, 95% CI: 1.6-2.6; P , 0.0001). Conclusion Right heart dysfunction is common in HFpEF and is caused by both RV contractile impairment and afterload mismatch from pulmonary hypertension. Right ventricular dysfunction in HFpEF develops with increasing PA pressures, atrial fibrillation, male sex, and left ventricular dysfunction, and may represent a novel therapeutic target.

Anti-inflammatory therapies for cardiovascular disease

Abstract: Atherothrombosis is no longer considered solely a disorder of lipoprotein accumulation in the arterial wall. Rather, the initiation and progression of atherosclerotic lesions is currently understood to have major inflammatory influences that encompass components of both the innate and acquired immune systems. Promising clinical data for ‘upstream’ biomarkers of inflammation such as interleukin-6 (IL-6) as well as ‘downstream’ biomarkers such as C-reactive protein, observations regarding cholesterol crystals as an activator of the IL-1β generating inflammasome, and recent Mendelian randomization data for the IL-6 receptor support the hypothesis that inflammatory mediators of atherosclerosis may converge on the central IL-1, tumour necrosis factor (TNF-α), IL-6 signalling pathway. On this basis, emerging anti-inflammatory approaches to vascular protection can be categorized into two broad groups, those that target the central IL-6 inflammatory signalling pathway and those that do not. Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). Both approaches have the potential to benefit patients and reduce vascular events. However, care should be taken when interpreting these trials as outcomes for agents that target IL-6 signalling are unlikely to be informative for therapies that target alternative pathways, and vice versa. As the inflammatory system is redundant, compensatory, and crucial for survival, evaluation of risks as well as benefits must drive the development of agents in this class.

Worldwide experience with a totally subcutaneous implantable defibrillator: early results from the EFFORTLESS S-ICD Registry.

Abstract: Aims The totally subcutaneous implantable-defibrillator (S-ICD) is a new alternative to the conventional transvenous ICD system to minimize intravascular lead complications. There are limited data describing the long-term performance of the S-ICD. This paper presents the first large international patient population collected as part of the EFFORTLESS S-ICD Registry. Methods and results The EFFORTLESS S-ICD Registry is a non-randomized, standard of care, multicentre Registry designed to collect long-term, system-related, clinical, and patient reported outcome data from S-ICD implanted patients since June 2009. Follow-up data are systematically collected over 60-month post-implant including Quality of Life. The study population of 472 patients of which 241 (51%) were enrolled prospectively has a mean follow-up duration of 558 days (range 13–1342 days, median 498 days), 72% male, mean age of 49 ± 18 years (range 9–88 years), 42% mean left ventricular ejection fraction. Complication-free rates were 97 and 94%, at 30 and 360 days, respectively. Three hundred and seventeen spontaneous episodes were recorded in 85 patients during the follow-up period. Of these episodes, 169 (53%) received therapy, 93 being for Ventricular Tachycardia/Fibrillation (VT/VF). One patient died of recurrent VF and severe bradycardia. Regarding discrete VT/VF episodes, first shock conversion efficacy was 88% with 100% overall successful clinical conversion after a maximum of five shocks. The 360-day inappropriate shock rate was 7% with the vast majority occurring for oversensing (62/73 episodes), primarily of cardiac signals (94% of oversensed episodes). Conclusion The first large cohort of real-world data from an International patient S-ICD population demonstrates appropriate system performance with clinical event rates and inappropriate shock rates comparable with those reported for conventional ICDs. Clinical trial registration URL: . Unique identifier [NCT01085435][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01085435&atom=%2Fehj%2F35%2F25%2F1657.atom

Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study

Abstract: Aims To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT). Methods and results We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels. Conclusions The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

Mechanical circulatory support in cardiogenic shock

Abstract: Despite advances in coronary revascularization and widespread use of primary percutaneous interventions, cardiogenic shock complicating an acute ST-elevation myocardial infarction (CSMI) remains a clinical challenge with high mortality rates. Conservative management with catecholamines is associated with serious limitations, including arrhythmias, increased myocardial oxygen consumption, and inadequate circulatory support. Clinicians have therefore turned to mechanical means of circulatory support. Circulatory assist systems for CSMI can be distinguished by the method of placement (i.e. percutaneous vs. surgical), the type of circulatory support (i.e. left ventricular, right ventricular, or biventricular pressure and/or volume unloading), and whether they are combined with extracorporal membrane oxygenation (ECMO). The percutaneous assist systems most commonly used in CSMI are the intra-aortic balloon pump (IABP), venoarterial ECMO, the Impella pump, and the TandemHeart. Decades of clinical studies and experience demonstrated haemodynamic improvement, including elevation of diastolic perfusion pressure and cardiac output. Recently, the large randomized IABP-Shock II Trial did not show a significant reduction in 30-day mortality in CSMI with IABP insertion. There are no randomized study data available for ECMO use in CSMI. Both the Impella pump and the TandemHeart did not reduce 30-day mortality when compared with IABP in small randomized controlled trials (RCTs). In conclusion, despite the need for effective mechanical circulatory support in CSMI, current devices, as tested, have not been demonstrated to improve short- or long-term survival rates. RCTs testing the optimal timing of device therapy and optimal device design are needed to improve outcomes in CSMI.

Biomechanical factors in atherosclerosis: mechanisms and clinical implications.

Abstract: Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors-mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current 'state of the art' on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future research.

Risk stratification for sudden cardiac death: current status and challenges for the future

Abstract: Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds.

Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation

Abstract: Aims X-VeRT is the first prospective randomized trial of a novel oral anticoagulant in patients with atrial fibrillation undergoing elective cardioversion. Methods and results We assigned 1504 patients to rivaroxaban (20 mg once daily, 15 mg if creatinine clearance was between 30 and 49 mL/min) or dose-adjusted vitamin K antagonists (VKAs) in a 2:1 ratio. Investigators selected either an early (target period of 1–5 days after randomization) or delayed (3–8 weeks) cardioversion strategy. The primary efficacy outcome was the composite of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, and cardiovascular death. The primary safety outcome was major bleeding. The primary efficacy outcome occurred in 5 (two strokes) of 978 patients (0.51%) in the rivaroxaban group and in 5 (two strokes) of 492 patients (1.02%) in the VKA group [risk ratio 0.50; 95% confidence interval (CI) 0.15–1.73]. In the rivaroxaban group, four patients experienced primary efficacy events following early cardioversion (0.71%) and one following delayed cardioversion (0.24%). In the VKA group, three patients had primary efficacy events following early cardioversion (1.08%) and two following delayed cardioversion (0.93%). Rivaroxaban was associated with a significantly shorter time to cardioversion compared with VKAs ( P < 0.001). Major bleeding occurred in six patients (0.6%) in the rivaroxaban group and four patients (0.8%) in the VKA group (risk ratio 0.76; 95% CI 0.21–2.67). Conclusion Oral rivaroxaban appears to be an effective and safe alternative to VKAs and may allow prompt cardioversion. Name of the trial registry Clinicaltrials.gov; Trial registration number: [NCT01674647][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01674647&atom=%2Fehj%2F35%2F47%2F3346.atom

Device-detected atrial fibrillation and risk for stroke: an analysis of >10 000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices)

Abstract: Objective The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke. Background Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden. Design, setting, and patients A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed. Results During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3–14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22–3.64, P = 0.008). Conclusions Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment.

Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry

Abstract: Aims Patients receiving novel oral anticoagulants (NOACs) frequently undergo interventional procedures. Short half-lives and rapid onset of action allow for short periods of NOAC interruption without heparin bridging. However, outcome data for this approach are lacking. We evaluated the peri-interventional NOAC management in unselected patients from daily care. Methods and results Effectiveness and safety data were collected from an ongoing, prospective, non-interventional registry of >2100 NOAC patients. Outcome events were adjudicated using standard event definitions. Of 2179 registered patients, 595 (27.3%) underwent 863 procedures (15.6% minimal, 74.3% minor, and 10.1% major procedures). Until Day 30 ± 5 post-procedure, major cardiovascular events occurred in 1.0% of patients [95% confidence interval (95% CI) 0.5–2.0] and major bleeding complications in 1.2% (95% CI 0.6–2.1). Cardiovascular and major bleeding complications were highest after major procedures (4.6 and 8.0%, respectively). Heparin bridging did not reduce cardiovascular events, but led to significantly higher rates of major bleeding complications (2.7%; 95% CI 1.1–5.5) compared with no bridging (0.5%; 0.1–1.4; P = 0.010). Multivariate analysis demonstrated diabetes [odds ratio (OR) 13.2] and major procedures (OR 7.3) as independent risk factors for cardiovascular events. Major procedures (OR 16.8) were an independent risk factor for major bleeding complications. However, if major and non-major procedures were separately assessed, heparin bridging was not an independent risk factor for major bleeding. Conclusion Continuation or short-term interruption of NOAC is safe strategies for most invasive procedures. Patients at cardiovascular risk undergoing major procedures may benefit from heparin bridging, but bleeding risks need to be considered.

Management of venous thrombo-embolism: an update

Abstract: Venous thrombo-embolism is the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke. Recently published landmark trials paved the way for significant progress in the management of the disease and provided the evidence for the ESC Pulmonary Embolism (PE) Guidelines 2014 update. Risk stratification strategies for non-high-risk PE continue to evolve, with an increasing emphasis on clinical prediction rules and right ventricular (RV) assessment on computed tomographic pulmonary angiography. In the field of anticoagulation treatment, pharmacogenetic testing for vitamin K antagonists on top of clinical parameters was not found to offer a significant benefit during the initiation phase; on the other hand, dosing based on the patient's clinical data seems superior to fixed loading regimens. The phase 3 trial programme of new oral anticoagulants in the treatment of venous thrombo-embolism has been completed, and the results indicate that these agents are at least as effective and probably cause less major bleeding than currently standard treatment. A multicentre prospective phase 4 trial will determine whether early discharge and out-of-hospital treatment of low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. For intermediate-risk PE defined on the basis of imaging tests and laboratory biomarkers, the bleeding risks of full-dose thrombolytic treatment appear too high to justify its use, unless clinical signs of haemodynamic decompensation appear. Patients in whom PE has resulted in chronic thrombo-embolic pulmonary hypertension and who are not suitable for pulmonary endarterectomy, may be expected to benefit from emerging pharmaceutical and interventional treatment options.

Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission

Abstract: We enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression mod- elled mortality and/or hospitalization for heart failure. Diabetic individuals (n ¼ 231) had higher median ECV than those without diabetes (n ¼ 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P , 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P , 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P ¼ 0.028) in multivari- able linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitaliza- tions for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models. Conclusion Diabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion asso- ciated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is de- tectable and treatable.