Showing papers in "European Heart Journal in 2012"

ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation

Abstract: ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ADP : adenosine diphosphate AF : atrial fibrillation AMI : acute myocardial infarction AV : atrioventricular AIDA-4 : Abciximab Intracoronary vs. intravenously Drug Application APACHE II : Acute Physiology Aand Chronic

European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012)

Abstract: ABI : ankle–brachial index ACCORD : Action to Control Cardiovascular Risk in Diabetes ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AGREE : Appraisal of Guidelines Research and Evaluation AHA : American Heart Association apoA1 : apolipoprotein A1 apoB : apolipoprotein B CABG : coronary artery bypass graft surgery CARDS : Collaborative AtoRvastatin Diabetes Study CCNAP : Council on Cardiovascular Nursing and Allied Professions CHARISMA : Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance CHD : coronary heart disease CKD : chronic kidney disease COMMIT : Clopidogrel and Metoprolol in Myocardial Infarction Trial CRP : C-reactive protein CURE : Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD : cardiovascular disease DALYs : disability-adjusted life years DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Trial ED : erectile dysfunction eGFR : estimated glomerular filtration rate EHN : European Heart Network EPIC : European Prospective Investigation into Cancer and Nutrition EUROASPIRE : European Action on Secondary and Primary Prevention through Intervention to Reduce Events GFR : glomerular filtration rate GOSPEL : Global Secondary Prevention Strategies to Limit Event Recurrence After MI GRADE : Grading of Recommendations Assessment, Development and Evaluation HbA1c : glycated haemoglobin HDL : high-density lipoprotein HF-ACTION : Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing HOT : Hypertension Optimal Treatment Study HPS : Heart Protection Study HR : hazard ratio hsCRP : high-sensitivity C-reactive protein HYVET : Hypertension in the Very Elderly Trial ICD : International Classification of Diseases IMT : intima-media thickness INVEST : International Verapamil SR/Trandolapril JTF : Joint Task Force LDL : low-density lipoprotein Lp(a) : lipoprotein(a) LpPLA2 : lipoprotein-associated phospholipase 2 LVH : left ventricular hypertrophy MATCH : Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke MDRD : Modification of Diet in Renal Disease MET : metabolic equivalent MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease NICE : National Institute of Health and Clinical Excellence NRT : nicotine replacement therapy NSTEMI : non-ST elevation myocardial infarction ONTARGET : Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial OSA : obstructive sleep apnoea PAD : peripheral artery disease PCI : percutaneous coronary intervention PROactive : Prospective Pioglitazone Clinical Trial in Macrovascular Events PWV : pulse wave velocity QOF : Quality and Outcomes Framework RCT : randomized clinical trial RR : relative risk SBP : systolic blood pressure SCORE : Systematic Coronary Risk Evaluation Project SEARCH : Study of the Effectiveness of Additional Reductions in Cholesterol and SHEP : Systolic Hypertension in the Elderly Program STEMI : ST-elevation myocardial infarction SU.FOL.OM3 : SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids Syst-Eur : Systolic Hypertension in Europe TNT : Treating to New Targets UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use VITATOPS : VITAmins TO Prevent Stroke VLDL : very low-density lipoprotein WHO : World Health Organization ### 1.1 Introduction Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …

ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

Abstract: ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 : The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC

Guidelines on the management of valvular heart disease (version 2012)

Abstract: ACE : angiotensin-converting enzyme AF : atrial fibrillation aPTT : activated partial thromboplastin time AR : aortic regurgitation ARB : angiotensin receptor blockers AS : aortic stenosis AVR : aortic valve replacement BNP : B-type natriuretic peptide BSA : body surface area CABG : coronary artery bypass grafting CAD : coronary artery disease CMR : cardiac magnetic resonance CPG : Committee for Practice Guidelines CRT : cardiac resynchronization therapy CT : computed tomography EACTS : European Association for Cardio-Thoracic Surgery ECG : electrocardiogram EF : ejection fraction EROA : effective regurgitant orifice area ESC : European Society of Cardiology EVEREST : (Endovascular Valve Edge-to-Edge REpair STudy) HF : heart failure INR : international normalized ratio LA : left atrial LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction LVEDD : left ventricular end-diastolic diameter LVESD : left ventricular end-systolic diameter MR : mitral regurgitation MS : mitral stenosis MSCT : multi-slice computed tomography NYHA : New York Heart Association PISA : proximal isovelocity surface area PMC : percutaneous mitral commissurotomy PVL : paravalvular leak RV : right ventricular rtPA : recombinant tissue plasminogen activator SVD : structural valve deterioration STS : Society of Thoracic Surgeons TAPSE : tricuspid annular plane systolic excursion TAVI : transcatheter aortic valve implantation TOE : transoesophageal echocardiography TR : tricuspid regurgitation TS : tricuspid stenosis TTE : transthoracic echocardiography UFH : unfractionated heparin VHD : valvular heart disease 3DE : three-dimensional echocardiography Guidelines summarize and evaluate all evidence available, 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 …

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

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

Nitric oxide synthases: regulation and function.

Abstract: Nitric oxide (NO), the smallest signalling molecule known, is produced by three isoforms of NO synthase (NOS; EC 1.14.13.39). They all utilize l-arginine and molecular oxygen as substrates and require the cofactors reduced nicotinamide-adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and (6R-)5,6,7,8-tetrahydrobiopterin (BH(4)). All NOS bind calmodulin and contain haem. Neuronal NOS (nNOS, NOS I) is constitutively expressed in central and peripheral neurons and some other cell types. Its functions include synaptic plasticity in the central nervous system (CNS), central regulation of blood pressure, smooth muscle relaxation, and vasodilatation via peripheral nitrergic nerves. Nitrergic nerves are of particular importance in the relaxation of corpus cavernosum and penile erection. Phosphodiesterase 5 inhibitors (sildenafil, vardenafil, and tadalafil) require at least a residual nNOS activity for their action. Inducible NOS (NOS II) can be expressed in many cell types in response to lipopolysaccharide, cytokines, or other agents. Inducible NOS generates large amounts of NO that have cytostatic effects on parasitic target cells. Inducible NOS contributes to the pathophysiology of inflammatory diseases and septic shock. Endothelial NOS (eNOS, NOS III) is mostly expressed in endothelial cells. It keeps blood vessels dilated, controls blood pressure, and has numerous other vasoprotective and anti-atherosclerotic effects. Many cardiovascular risk factors lead to oxidative stress, eNOS uncoupling, and endothelial dysfunction in the vasculature. Pharmacologically, vascular oxidative stress can be reduced and eNOS functionality restored with renin- and angiotensin-converting enzyme-inhibitors, with angiotensin receptor blockers, and with statins.

Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study

Abstract: Aims The impact of some risk factors for stroke and bleeding, and the value of stroke and bleeding risk scores, in atrial fibrillation (AF), has been debated, as clinical trial cohorts have not adequately tested these. Our objective was to investigate risk factors for stroke and bleeding in AF, and application of the new CHA2DS2-VASc and HAS-BLED schemes for stroke and bleeding risk assessments, respectively. Methods and results We used the Swedish Atrial Fibrillation cohort study, a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008, who were prospectively followed for an average of 1.5 years (260 000 years at risk). With the use of the National Swedish Drug Registry, all patients who used an oral anticoagulant anytime during follow-up were identified. Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants. Risk factors for stroke, the composite thromboembolism endpoint (stroke, TIA, or systemic embolism), and bleeding, and the performance of published stroke and bleeding risk stratification schemes were investigated. On multivariable analysis, significant associations were found between the following ‘new’ risk factors and thromboembolic events; peripheral artery disease [hazard ratio (HR) 1.22 (95% CI 1.12–1.32)], ‘vascular disease’ [HR 1.14 (1.06–1.23)], prior myocardial infarction [HR 1.09 (1.03–1.15)], and female gender [HR 1.17 (1.11–1.22)]. Previous embolic events, intracranial haemorrhage (ICH), hypertension, diabetes, and renal failure were other independent predictors of the composite thromboembolism endpoint, while thyroid disease (or hyperthyroidism) was not an independent stroke risk factor. C-statistics for the composite thromboembolic endpoint with the CHADS2 and CHA2DS2-VASc schemes were 0.66 (0.65–0.66) and 0.67 (0.67–0.68), respectively. On multivariable analysis, age, prior ischaemic stroke or thromboembolism, prior major bleeding events, and hypertension were significant predictors of ICH and major bleeding. Heart failure, diabetes, renal failure, liver disease, anaemia or platelet/coagulation defect, alcohol abuse, and cancer were other significant predictors for major bleeding, but not ICH. The ability for predicting ICH and major bleeding with both bleeding risk schemes (HEMORR2HAGES, HAS-BLED) were similar, with c-statistics of ∼0.6. Conclusion Several independent risk factors (prior ICH, myocardial infarction, vascular disease, and renal failure) predict ischaemic stroke and/or the composite thromboembolism endpoint in AF, but thyroid disease (or hyperthyroidism) was not an independent risk factor for stroke. There is a better performance for CHA2DS2-VASc over CHADS2 schemes for the composite thromboembolism endpoint. While both tested bleeding risk schemes have similar predictive value, the HAS-BLED score has the advantage of simplicity.

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events

Abstract: Aims Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. Methods and results We identified 11 223 patients referred for coronary angiography (CAG) in 1998–2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD ( P < 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27–1.83) for patients with normal coronary arteries and 1.85 (1.51–2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07–1.56) and 1.52 (1.24–1.88), respectively. Conclusion Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

How to use high-sensitivity cardiac troponins in acute cardiac care

Abstract: Recommendations for the use of cardiac troponin (cTn) measurement in acute cardiac care have recently been published.1 Subsequently, a high-sensitivity (hs) cTn T assay was introduced into routine clinical practice.2 This assay, as others, called highly sensitive, permits measurement of cTn concentrations in significant numbers of apparently illness-free individuals. These assays can measure cTn in the single digit range of nanograms per litre (=picograms per millilitre) and some research assays even allow detection of concentrations 10% at the 99th percentile URL limiting that ability.5–7 However, the less precise cTn assays do not cause clinically relevant false-positive diagnosis of acute myocardial infarction (AMI) and a CV <20% at the 99th percentile URL is still considered acceptable.8 We believe that hs-cTn assays, if used appropriately, will improve clinical care. We propose criteria for the clinical interpretation of test results based on the limited evidence available at this time. ‘Sensitive’ and ‘high-sensitive’ are terms often used by manufacturers to describe their assays for marketing purposes. In some cases, it reflects higher sensitivity than former assays developed by the same company, and in other situations it reflects a higher sensitivity than most assays on the market. Although there is still no consensus regarding when the terms ‘sensitive’ and ‘high-sensitive’ should be applied, we advocate that cTn assays should be labelled ‘high-sensitive’ only if they fulfil the analytical criteria suggested by …

Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes

Abstract: Aims Endurance training may be associated with arrhythmogenic cardiac remodelling of the right ventricle (RV). We examined whether myocardial dysfunction following intense endurance exercise affects the RV more than the left ventricle (LV) and whether cumulative exposure to endurance competition influences cardiac remodelling (including fibrosis) in well-trained athletes. Methods and results Forty athletes were studied at baseline, immediately following an endurance race (3–11 h duration) and 1-week post-race. Evaluation included cardiac troponin (cTnI), B-type natriuretic peptide, and echocardiography [including three-dimensional volumes, ejection fraction (EF), and systolic strain rate]. Delayed gadolinium enhancement (DGE) on cardiac magnetic resonance imaging (CMR) was assessed as a marker of myocardial fibrosis. Relative to baseline, RV volumes increased and all functional measures decreased post-race, whereas LV volumes reduced and function was preserved. B-type natriuretic peptide (13.1 ± 14.0 vs. 25.4 ± 21.4 ng/L, P = 0.003) and cTnI (0.01 ± .03 vs. 0.14 ± .17 μg/L, P < 0.0001) increased post-race and correlated with reductions in RVEF ( r = 0.52, P = 0.001 and r = 0.49, P = 0.002, respectively), but not LVEF. Right ventricular ejection fraction decreased with increasing race duration ( r = −0.501, P < 0.0001) and VO2max ( r = −0.359, P = 0.011). Right ventricular function mostly recovered by 1 week. On CMR, DGE localized to the interventricular septum was identified in 5 of 39 athletes who had greater cumulative exercise exposure and lower RVEF (47.1 ± 5.9 vs. 51.1 ± 3.7%, P = 0.042) than those with normal CMR. Conclusion Intense endurance exercise causes acute dysfunction of the RV, but not the LV. Although short-term recovery appears complete, chronic structural changes and reduced RV function are evident in some of the most practiced athletes, the long-term clinical significance of which warrants further study.

Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry.

Abstract: Aims Men and women differ in terms of presentation and management in coronary artery disease (CAD). Whether these differences translate into different clinical outcomes in stable CAD is unclear. We analysed data from the international prospective CLARIFY registry to compare cardiovascular clinical outcomes in men and women with stable CAD. Methods and results We analysed 1-year outcomes in 30 977 outpatients with stable CAD [23 975 (77.4%) men; 7002 (22.6%) women]. Women were older than men, more likely to have hypertension and diabetes, and less likely to exercise or smoke. They had more frequent angina, but were less likely to have undergone diagnostic non-invasive testing or coronary angiography. Women received less optimized treatment for stable CAD. One-year outcomes were similar for men and women for the composite of cardiovascular death, non-fatal myocardial infarction, or stroke [adjusted rates 1.7 vs. 1.8%, respectively, odds ratio (OR) 0.93, 95% confidence interval (CI) 0.75–1.15]; all-cause death (adjusted 1.5 vs. 1.6%, OR: 0.91, 95% CI: 0.72–1.13); fatal or non-fatal myocardial infarction (adjusted 1.0 vs. 0.9%, OR: 0.81, 95 CI: 0.60–1.08); and cardiovascular death or non-fatal myocardial infarction (adjusted 1.4 vs. 1.4%, OR: 0.89, 95% CI: 0.70–1.12). Fewer women underwent revascularization (2.6 vs. 2.2%, OR: 0.77, 95% CI: 0.64–0.93), although appropriateness was not analysed. Conclusion The risk profiles of women and men with stable CAD differ substantially. However, 1-year outcomes were similar. Fewer women underwent revascularization. Further research is needed to better understand gender determinants of outcome and devise strategies to minimize bias in the management and treatment of women.

Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology

Abstract: Aims Conventional late gadolinium enhancement (LGE) cardiac magnetic resonance can detect myocardial infarction and some forms of non-ischaemic myocardial fibrosis. However, quantitative imaging of extracellular volume fraction (ECV) may be able to detect subtle abnormalities such as diffuse fibrosis or post-infarct remodelling of remote myocardium. The aims were (1) to measure ECV in myocardial infarction and non-ischaemic myocardial fibrosis, (2) to determine whether ECV varies with age, and (3) to detect sub-clinical abnormalities in ‘normal appearing’ myocardium remote from regions of infarction. Methods and results Cardiac magnetic resonance ECV imaging was performed in 126 patients with T1 mapping before and after injection of gadolinium contrast. Conventional LGE images were acquired for the left ventricle. In patients with a prior myocardial infarction, the infarct region had an ECV of 51 ± 8% which did not overlap with the remote ‘normal appearing’ myocardium that had an ECV of 27 ± 3% ( P < 0.001, n = 36). In patients with non-ischaemic cardiomyopathy, the ECV of atypical LGE was 37 ± 6%, whereas the ‘normal appearing’ myocardium had an ECV of 26 ± 3% ( P < 0.001, n = 30). The ECV of ‘normal appearing’ myocardium increased with age ( r = 0.28, P = 0.01, n = 60). The ECV of ‘normal appearing’ myocardium remote from myocardial infarctions increased as left ventricular ejection fraction decreased ( r = −0.50, P = 0.02). Conclusion Extracellular volume fraction imaging can quantitatively characterize myocardial infarction, atypical diffuse fibrosis, and subtle myocardial abnormalities not clinically apparent on LGE images. Taken within the context of prior literature, these subtle ECV abnormalities are consistent with diffuse fibrosis related to age and changes remote from infarction.

Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial.

Abstract: Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the AR- ISTOTLE trial. We evaluated these outcomes in relation to renal function. Methods and results Baseline glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cock- croft-Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of .80 mL/min, 7587 (42%) between .50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft- Gault {hazard ratio (HR) 0.50 (95% confidence interval (CI) 0.38-0.66), interaction P ¼ 0.005} or CKD-EPI equations (HR 0.48 (95% CI 0.37-0.64), interaction P ¼ 0.003). Conclusion In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.

Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction

Abstract: Aims Exenatide, a glucagon-like-peptide-1 analogue, increases myocardial salvage in experimental settings with coronary occlusion and subsequent reperfusion. We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods and results A total of 172 patients with STEMI and Thrombolysis in Myocardial Infarction flow 0/1 were randomly assigned to exenatide or placebo (saline) intravenously. Study treatment was commenced 15 min before intervention and maintained for 6 h after the procedure. The primary endpoint was salvage index calculated from myocardial area at risk (AAR), measured in the acute phase, and final infarct size measured 90 ± 21 days after pPCI by cardiac magnetic resonance (CMR). In 105 patients evaluated with CMR, a significantly larger salvage index was found in the exenatide group than in the placebo group (0.71 ± 0.13 vs. 0.62 ± 0.16; P = 0.003). Infarct size in relation to AAR was also smaller in the exenatide group (0.30 ± 0.15 vs. 0.39 ± 0.15; P = 0.003). In a regression analysis, there was a significant correlation between the infarct size and the AAR for both treatment groups and an analysis of covariance showed that datapoints in the exenatide group lay significantly lower than for the placebo group ( P = 0.011). There was a trend towards smaller absolute infarct size in the exenatide group (13 ± 9 vs. 17 ± 14 g; P = 0.11). No difference was observed in left ventricular function or 30-day clinical events. No adverse effects of exenatide were observed. Conclusion In patients with STEMI undergoing pPCI, administration of exenatide at the time of reperfusion increases myocardial salvage.

The human sympathetic nervous system: its relevance in hypertension and heart failure

Abstract: Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this ‘ mechanisms to management ’ transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in hypertension pathogenesis, and perhaps suggests a wider role for anti-adrenergic antihypertensives, such as the imidazoline drug class (moxonidine, rilmenidine) which act within the CNS to inhibit central sympathetic outflow, although the lack of large-scale outcome trials with this drug class remains a very material deficiency.

A novel clinical method for quantification of regional left ventricular pressure–strain loop area: a non-invasive index of myocardial work

Abstract: Aims Left ventricular (LV) pressure–strain loop area reflects regional myocardial work and metabolic demand, but the clinical use of this index is limited by the need for invasive pressure. In this study, we introduce a non-invasive method to measure LV pressure–strain loop area. Methods and results Left ventricular pressure was estimated by utilizing the profile of an empiric, normalized reference curve which was adjusted according to the duration of LV isovolumic and ejection phases, as defined by timing of aortic and mitral valve events by echocardiography. Absolute LV systolic pressure was set equal to arterial pressure measured invasively in dogs ( n = 12) and non-invasively in patients ( n = 18). In six patients, myocardial glucose metabolism was measured by positron emission tomography (PET). First, we studied anaesthetized dogs and observed an excellent correlation ( r = 0.96) and a good agreement between estimated LV pressure–strain loop area and loop area by LV micromanometer and sonomicrometry. Secondly, we validated the method in patients with various cardiac disorders, including LV dyssynchrony, and confirmed an excellent correlation ( r = 0.99) and a good agreement between pressure–strain loop areas using non-invasive and invasive LV pressure. Non-invasive pressure–strain loop area reflected work when incorporating changes in local LV geometry ( r = 0.97) and showed a strong correlation with regional myocardial glucose metabolism by PET ( r = 0.81). Conclusions The novel non-invasive method for regional LV pressure–strain loop area corresponded well with invasive measurements and with directly measured myocardial work and it reflected myocardial metabolism. This method for assessment of regional work may be of clinical interest for several patients groups, including LV dyssynchrony and ischaemia.

Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?

Abstract: Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.

The impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27 186 patients with 133 141 patient-years.

Abstract: Aims Numerous studies have linked prosthesis–patient mismatch (PPM) after aortic valve replacement (AVR) to adverse outcomes. Its correlation with long-term survival has been described but with contradicting results. This systematic review and meta-analysis of observational studies aims to determine the hazard of PPM after AVR. Methods and results The Medline and EMBase databases were searched for English-language original publications. Two researchers independently screened studies and extracted data. Pooled estimates were obtained by random effects model. Subgroup analyses were performed to detect sources of heterogeneity. The search yielded 348 potentially relevant studies; 34 were included comprising 27 186 patients and 133 141 patient-years. Defined by the universally accredited indexed effective orifice area <0.85 cm2/m2, 44.2% of patients were categorized as having PPM. In 34.2 and 9.8% of patients moderate (0.65–0.85 cm2/m2) and severe (<0.65 cm2/m2) PPM was present, respectively. Prosthesis–patient mismatch was associated with a statistically significant increase in all-cause mortality (HR = 1.34, 95% CI: 1.18–1.51), but only a trend to an increase in cardiac-related mortality (HR = 1.51, 95% CI: 0.88–2.60) was recognized. Analysis by severity of PPM demonstrated that both moderate and severe PPM increased all-cause mortality (HR = 1.19, 95% CI: 1.07–1.33 and HR = 1.84, 95% CI: 1.38–2.45) and cardiac-related mortality (HR = 1.32, 95% CI: 1.02–1.71 and HR = 6.46, 95% CI: 2.79–14.97). Further analyses showed a consistent effect over separate time intervals during follow-up. Conclusion Prosthesis–patient mismatch is associated with an increase in all-cause and cardiac-related mortality over long-term follow-up. We recommend that current efforts to prevent PPM should receive more emphasis and a widespread acceptance to improve long-term survival after AVR.

Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin–angiotensin–aldosterone system inhibitors involving 158 998 patients

Abstract: AimsRenin-Angiotensin-Aldosterone system (RAAS) inhibitors are well established for the reduction in cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients is uncertain. Our objective was to analyse the effects of RAAS inhibitors as a class of drugs, as well as of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) separately, on all-cause mortality. Methods and resultsWe performed a pooled analysis of 20 cardiovascular morbiditymortality trials. In each trial at least two-thirds of the patients had to be diagnosed with hypertension, according to the trial-specific definition, and randomized to treatment with an RAAS inhibitor or control treatment. The cohort included 158 998 patients (71 401 RAAS inhibitor; 87 597 control). The incidence of all-cause death was 20.9 and 23.3 per 1000 patient-years in patients randomized to RAAS inhibition and controls, respectively. Overall, RAAS inhibition was associated with a 5 reduction in all-cause mortality (HR: 0.95, 95 CI: 0.911.00, P = 0.032), and a 7 reduction in cardiovascular mortality (HR: 0.93, 95 CI: 0.880.99, P = 0.018). The observed treatment effect resulted entirely from the class of ACE inhibitors, which were associated with a significant 10 reduction in all-cause mortality (HR: 0.90, 95 CI: 0.840.97, P = 0.004), whereas no mortality reduction could be demonstrated with ARB treatment (HR: 0.99, 95 CI: 0.941.04, P = 0.683). This difference in treatment effect between ACE inhibitors and ARBs on all-cause mortality was statistically significant (P-value for heterogeneity 0.036). ConclusionIn patients with hypertension, treatment with an ACE inhibitor results in a significant further reduction in all-cause mortality. Because of the high prevalence of hypertension, the widespread use of ACE inhibitors may result in an important gain in lives saved.

Contrast-induced kidney injury: Mechanisms, risk factors, and prevention

Abstract: In general, iodinated contrast media (CM) are tolerated well, and CM use is steadily increasing. Acute kidney injury is the leading life-threatening side effect of CM. Here, we highlight endpoints used to assess CM-induced acute kidney injury (CIAKI), CM types, risk factors, and CIAKI prevention. Moreover, we put forward a unifying theory as to how CIAKI comes about; the kidney medulla's unique hyperosmolar environment concentrates CM in the tubules and vasculature. Highly concentrated CM in the tubules and vessels increases fluid viscosity. Thus, flow through medullary tubules and vessels decreases. Reducing the flow rate will increase the contact time of cytotoxic CM with the tubular epithelial cells and vascular endothelium, and thereby damage cells and generate oxygen radicals. As a result, medullary vasoconstriction takes place, causing hypoxia. Moreover, the glomerular filtration rate declines due to congestion of highly viscous tubular fluid. Effective prevention aims at reducing the medullary concentration of CM, thereby diminishing fluid viscosity. This is achieved by generous hydration using isotonic electrolyte solutions. Even forced diuresis may prove efficient if accompanied by adequate volume supplementation. Limiting the CM dose is the most effective measure to diminish fluid viscosity and to reduce cytotoxic effects.

Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials.

Abstract: Aims The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). Methods and results We pooled individual patient data from three large-scale multicentre randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4, and LEADERS) comparing biodegradable polymer DES with durable polymer SES and assessed clinical outcomes during follow-up through 4 years. The efficacy endpoint of interest was target lesion revascularization and the safety endpoint of interest was definite stent thrombosis. Out of 4062 patients included in the present analysis, 2358 were randomly assigned to treatment with biodegradable polymer DES (sirolimus-eluting, n = 1501; biolimus-eluting, n = 857) and 1704 patients to durable polymer SES. No heterogeneity across the trials was observed in analyses of the primary and secondary endpoints. At 4 years, the risk of target lesion revascularization was significantly lower among patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.82, 95% CI 0.68–0.98, P = 0.029). In addition, the risk of stent thrombosis was significantly reduced with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.56, 95% CI 0.35–0.90, P = 0.015), driven by a lower risk of very late stent thrombosis (hazard ratio 0.22, 95% CI 0.08–0.61, P = 0.004). In keeping with this, in landmark analysis between 1 and 4 years, the incidence of myocardial infarction was lower for patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.59, 95% CI 0.73–0.95, P = 0.031). Conclusion Biodegradable polymer DES improve safety and efficacy compared with durable polymer SES during long-term follow-up to 4 years.

The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities

Abstract: The conventional reporting of composite endpoints in clinical trials has an inherent limitation in that it emphasizes each patient's first event, which is often the outcome of lesser clinical importance. To overcome this problem, we introduce the concept of the win ratio for reporting composite endpoints. Patients in the new treatment and control groups are formed into matched pairs based on their risk profiles. Consider a primary composite endpoint, e.g. cardiovascular (CV) death and heart failure hospitalization (HF hosp) in heart failure trials. For each matched pair, the new treatment patient is labelled a 'winner' or a 'loser' depending on who had a CV death first. If that is not known, only then they are labelled a 'winner' or 'loser' depending on who had a HF hosp first. Otherwise they are considered tied. The win ratio is the total number of winners divided by the total numbers of losers. A 95% confidence interval and P-value for the win ratio are readily obtained. If formation of matched pairs is impractical then an alternative win ratio can be obtained by comparing all possible unmatched pairs. This method is illustrated by re-analyses of the EMPHASIS-HF, PARTNER B, and CHARM trials. The win ratio is a new method for reporting composite endpoints, which is easy to use and gives appropriate priority to the more clinically important event, e.g. mortality. We encourage its use in future trial reports.

Thoracic Endovascular Aortic Repair (TEVAR) for the treatment of aortic diseases: a position statement from the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Abstract: Thoracic endovascular aortic repair (TEVAR) is an emerging treatment modality, which has been rapidly embraced by clinicians treating thoracic aortic disease.1–4 Fundamentally, it is a far less invasive approach than open surgery and its availability and relative ease of application has changed and extended management options in thoracic aortic disease, including in those patients deemed unfit or unsuitable for open surgery. In the operating room, this requires considerable perceptual, cognitive and psychomotor demands on the operators. The dramatic expansion of TEVAR activity has necessarily prompted a requirement to systematically consider the indications, appropriateness, limitations and delivery of this treatment, which has been adopted by many specialties including cardiologists, cardiovascular surgeons, radiologists and vascular surgeons.5 Our task has been to generate a multidisciplinary position statement that supports and advises all clinicians utilizing this technological advance. This document focuses on the main diagnoses—thoracic aortic aneurysm (TAA), thoracic aortic dissection (TAD) of the descending aorta (type B according to the Stanford classification) and thoracic aortic injury (TAI)—indications and applicability of TEVAR and includes information regarding its limitations and complications. It acts as a position statement for both societies that reflects current understanding of thoracic aortic endovascular therapy. ### Evaluation of symptoms and patient status Symptoms in patients with TAA and chronic dissection are rare and non-specific.6,7 New onset of hoarseness or dysphagia may suggest a developing aneurysm in the distal aortic arch and proximal descending aorta. Most asymptomatic cases are discovered incidentally, while symptomatic patients have usually developed complications. Even in patients with acute aortic syndromes, chest pain, back pain and signs of malperfusion are often misinterpreted due to lack of awareness. In cases of clinical suspicion, a computed tomography (CT)-angiography is the diagnostic modality of first choice. ### Multidisciplinary consultation Patient selection should be performed on an individual basis according to anatomy, pathology, comorbidity and …

Expert review document part 2: methodology, terminology and clinical applications of optical coherence tomography for the assessment of interventional procedures

Abstract: This document is complementary to an Expert Review Document on Optical Coherence Tomography (OCT) for the study of coronary arteries and atherosclerosis.1 The goal of this companion manuscript is to provide a practical guide framework for the appropriate use and reporting of the novel frequency domain (FD) OCT imaging to guide interventional procedures, with a particular interest on the comparison with intravascular ultrasound (IVUS).1–4 In the OCT Expert Review Document on Atherosclerosis, a comprehensive description of the physical principles for OCT imaging and time domain (TD) catheters (St Jude Medical, Westford, MA, USA) was provided.1 The main advantage of FD-OCT is that the technology enables rapid imaging of the coronary artery, using a non-occlusive acquisition modality. The FD-OCT catheter (DragonflyTM; St Jude Medical) employs a single-mode optical fibre, enclosed in a hollow metal torque wire that rotates at a speed of 100 r.p.s. It is compatible with a conventional 0.014″ angioplasty guide wire, inserted into a short monorail lumen at the tip. The frequency domain optical coherence tomography lateral resolution is improved in comparison with TD-OCT, while the axial resolution did not change. These features, together with reduced motion artefacts and an increased maximum field of view up to 11 mm, have significantly improved both the quality and ease of use of OCT in the catheterization laboratory.3,4 However, the imaging depth of the FD-OCT is still limited to 0.5–2.0 mm.5 The main obstacle to the adoption of TD-OCT imaging in clinical practice is that OCT cannot image through a blood field, and therefore requires clearing or flushing of blood from the lumen.1 The 6 Fr compatible DragonflyTM FD-OCT catheter is so far the only one in the market, as two other systems from Volcano and Terumo, which …

Lower risk of stent thrombosis and restenosis with unrestricted use of onew-generation' drug-eluting stents: a report from the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

Abstract: To compare the long-term outcome after percutaneous coronary intervention with onew-generation' drug-eluting stents (n-DES) to oolder generation' DES (o-DES), and bare-metal stents (BMS) in a real- ...

Reference values for exercise limitations among adults with congenital heart disease. Relation to activities of daily life--single centre experience and review of published data.

Abstract: Aims We aimed to investigate the distribution of exercise capacity across the spectrum of adult congenital heart disease (ACHD) using own data and the published experience and to provide diagnosis, gender-, and age- specific reference values. Methods and results Publications describing exercise capacity in ACHD patients using cardiopulmonary exercise testing (CPET) were identified ( n = 2286 patients in 23 papers). In addition, we included 2129 patients who underwent CPET at our own institution. The majority of patients (80%) had reduced peak oxygen uptake (peak VO2) compared with normal values (defined as <90% of predicted peak VO2). There were significant differences in peak VO2 between subgroups of patients, with the lowest values seen in patients with Eisenmenger syndrome and complex heart disease. However, even in patients with simple lesions, peak VO2 was on average significantly reduced compared with normal values. Based on a large number of observations we herewith provide gender- and age-specific peak VO2 centile plots for the most common lesions (Tetralogy of Fallot, systemic right ventricle, Ebstein anomaly and Fontan–palliation) and relate disease-specific exercise capacity to that required for specific activities of daily life, sports, and occupations. Conclusion We provide age-, gender-, and diagnosis-specific data on peak VO2 levels across the spectrum of ACHD allowing to compare the exercise capacity of individual patients with that of their peer patients. These data should be helpful in interpreting CPET results, guiding therapy, and advising patients on activities of daily life, sports participation, and choice of occupation.

Nurse-led care vs. usual care for patients with atrial fibrillation: results of a randomized trial of integrated chronic care vs. routine clinical care in ambulatory patients with atrial fibrillation

Abstract: The management of patients with atrial fibrillation (AF) is often inadequate due to deficient adherence to the guidelines. A nurse-led AF clinic providing integrated chronic care to improve guideline adherence and activate patients in their role, may effectively reduce morbidity and mortality but such care has not been tested in a large randomized trial. Therefore, we performed a randomized clinical trial to compare the AF clinic with routine clinical care in patients with AF. Methods and results We randomly assigned 712 patients with AF to nurse-led care and usual care. Nurse-led care consisted of guidelines based, software supported integrated chronic care supervised by a cardiologist. The primary endpoint was a compos- ite of cardiovascular hospitalization and cardiovascular death. Duration of follow-up was at least 12 months. Adher- ence to guideline recommendations was significantly better in the nurse-led care group. After a mean of 22 months, the primary endpoint occurred in 14.3% of 356 patients of the nurse-led care group compared with 20.8% of 356 patients receiving usual care (hazard ratio: 0.65; 95% confidence interval (CI) 0.45-0.93; P ¼ 0.017). Cardiovascular death occurred in 1.1% in the nurse-led care vs. 3.9% in the usual care group (hazard ratio: 0.28; 95% CI: 0.09-0.85; P ¼ 0.025). Cardiovascular hospitalization amounted (13.5 vs. 19.1%, respectively, hazard ratio: 0.66; 95% CI: 0.46- 0.96, P ¼ 0.029). Conclusion Nurse-led care of patients with AF is superior to usual care provided by a cardiologist in terms of cardiovascular hospitalizations and cardiovascular mortality.

Diastolic dysfunction and mortality in severe sepsis and septic shock

Abstract: Aims Systolic dysfunction in septic shock is well recognized and, paradoxically, predicts better outcome. In contrast, diastolic dysfunction is often ignored and its role in determining early mortality from sepsis has not been adequately investigated. Methods and results A cohort of 262 intensive care unit patients with severe sepsis or septic shock underwent two echocardiography examinations early in the course of their disease. All clinical, laboratory, and survival data were prospectively collected. Ninety-five (36%) patients died in the hospital. Reduced mitral annular e′-wave was the strongest predictor of mortality, even after adjusting for the APACHE-II score, low urine output, low left ventricular stroke volume index, and lowest oxygen saturation, the other independent predictors of mortality (Cox's proportional hazards: Wald = 21.5, 16.3, 9.91, 7.0 and 6.6, P < 0.0001, <0.0001, 0.002, 0.008, and 0.010, respectively). Patients with systolic dysfunction only (left ventricular ejection fraction ≤50%), diastolic dysfunction only (e′-wave <8 cm/s), or combined systolic and diastolic dysfunction (9.1, 40.4, and 14.1% of the patients, respectively) had higher mortality than those with no diastolic or systolic dysfunction (hazard ratio = 2.9, 6.0, 6.2, P = 0.035, <0.0001, <0.0001, respectively) and had significantly higher serum levels of high-sensitivity troponin-T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). High-sensitivity troponin-T was only minimally elevated, whereas serum levels of NT-proBNP were markedly elevated [median (inter-quartile range): 0.07 (0.02–0.17) ng/mL and 5762 (1001–15 962) pg/mL, respectively], though both predicted mortality even after adjusting for highest creatinine levels (Wald = 5.8, 21.4 and 2.3, P = 0.015, <0.001 and 0.13). Conclusion Diastolic dysfunction is common and is a major predictor of mortality in severe sepsis and septic shock.