Petros Nihoyannopoulos

ESC Guidelines for the diagnosis and

ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

ESC Guidelines for the diagnosis and

99mTc : technetium-99m 201TI : thallium 201 ABCB1 : ATP-binding cassette sub-family B member 1 ABI : ankle-brachial index ACC : American College of Cardiology ACCF : American College of Cardiology Foundation ACCOMPLISH : Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension ACE : angiotensin converting enzyme ACIP : Asymptomatic Cardiac Ischaemia Pilot ACS : acute coronary syndrome ADA : American Diabetes Association ADP : adenosine diphosphate AHA : American Heart Association ARB : angiotensin II receptor antagonist ART : Arterial Revascularization Trial ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASSERT : Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial AV : atrioventricular BARI 2D : Bypass Angioplasty Revascularization Investigation 2 Diabetes BEAUTIFUL : Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction BIMA : bilateral internal mammary artery BMI : body mass index BMS : bare metal stent BNP : B-type natriuretic peptide BP : blood pressure b.p.m. : beats per minute CABG : coronary artery bypass graft CAD : coronary artery disease CAPRIE : Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events CASS : Coronary Artery Surgery Study CCB : calcium channel blocker CCS : Canadian Cardiovascular Society CFR : coronary flow reserve CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance CI : confidence interval CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease Epidemiology Collaboration CMR : cardiac magnetic resonance CORONARY : The CABG Off or On Pump Revascularization Study COURAGE : Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation COX-1 : cyclooxygenase-1 COX-2 : cyclooxygenase-2 CPG : Committee for Practice Guidelines CT : computed tomography CTA : computed tomography angiography CV : cardiovascular CVD : cardiovascular disease CXR : chest X-ray CYP2C19*2 : cytochrome P450 2C19 CYP3A : cytochrome P3A CYP3A4 : cytochrome P450 3A4 CYP450 : cytochrome P450 DANAMI : Danish trial in Acute Myocardial Infarction DAPT : dual antiplatelet therapy DBP : diastolic blood pressure DECOPI : Desobstruction Coronaire en Post-Infarctus DES : drug-eluting stents DHP : dihydropyridine DSE : dobutamine stress echocardiography EACTS : European Association for Cardiothoracic Surgery EECP : enhanced external counterpulsation EMA : European Medicines Agency EASD : European Association for the Study of Diabetes ECG : electrocardiogram Echo : echocardiogram ED : erectile dysfunction EF : ejection fraction ESC : European Society of Cardiology EXCEL : Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization FAME : Fractional Flow Reserve vs. Angiography for Multivessel Evaluation FDA : Food & Drug Administration (USA) FFR : fractional flow reserve FREEDOM : Design of the Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease GFR : glomerular filtration rate HbA1c : glycated haemoglobin HDL : high density lipoprotein HDL-C : high density lipoprotein cholesterol HR : hazard ratio HRT : hormone replacement therapy hs-CRP : high-sensitivity C-reactive protein HU : Hounsfield units ICA : invasive coronary angiography IMA : internal mammary artery IONA : Impact Of Nicorandil in Angina ISCHEMIA : International Study of Comparative Health Effectiveness with Medical and Invasive Approaches IVUS : intravascular ultrasound JSAP : Japanese Stable Angina Pectoris KATP : ATP-sensitive potassium channels LAD : left anterior descending LBBB : left bundle branch block LIMA : Left internal mammary artery LDL : low density lipoprotein LDL-C : low density lipoprotein cholesterol LM : left main LMS : left main stem LV : left ventricular LVEF : left ventricular ejection fraction LVH : left ventricular hypertrophy MACE : major adverse cardiac events MASS : Medical, Angioplasty, or Surgery Study MDRD : Modification of Diet in Renal Disease MERLIN : Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes MERLIN-TIMI 36 : Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes: Thrombolysis In Myocardial Infarction MET : metabolic equivalents MI : myocardial infarction MICRO-HOPE : Microalbuminuria, cardiovascular and renal sub-study of the Heart Outcomes Prevention Evaluation study MPI : myocardial perfusion imaging MRI : magnetic resonance imaging NO : nitric oxide NSAIDs : non-steroidal anti-inflammatory drugs NSTE-ACS : non-ST-elevation acute coronary syndrome NYHA : New York Heart Association OAT : Occluded Artery Trial OCT : optical coherence tomography OMT : optimal medical therapy PAR-1 : protease activated receptor type 1 PCI : percutaneous coronary intervention PDE5 : phosphodiesterase type 5 PES : paclitaxel-eluting stents PET : positron emission tomography PRECOMBAT : Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease PTP : pre-test probability PUFA : polyunsaturated fatty acid PVD : peripheral vascular disease QoL : quality of life RBBB : right bundle branch block REACH : Reduction of Atherothrombosis for Continued Health RITA-2 : Second Randomized Intervention Treatment of Angina ROOBY : Veterans Affairs Randomized On/Off Bypass SAPT : single antiplatelet therapy SBP : systolic blood pressure SCAD : stable coronary artery disease SCORE : Systematic Coronary Risk Evaluation SCS : spinal cord stimulation SES : sirolimus-eluting stents SIMA : single internal mammary artery SPECT : single photon emission computed tomography STICH : Surgical Treatment for Ischaemic Heart Failure SWISSI II : Swiss Interventional Study on Silent Ischaemia Type II SYNTAX : SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery TC : total cholesterol TENS : transcutaneous electrical neural stimulation TERISA : Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina TIME : Trial of Invasive vs. Medical therapy TIMI : Thrombolysis In Myocardial Infarction TMR : transmyocardial laser revascularization TOAT : The Open Artery Trial WOEST : What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing 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 …

Guidelines and Expert Consensus Documents summarize and evaluate all available evidence 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 outcome and the risk–benefit ratio of diagnostic or therapeutic means. Guidelines are no substitutes for textbooks and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s). The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). Members of this Task Force were selected by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) to represent all physicians involved with the medical and surgical care of patients with coronary artery disease (CAD). A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for society are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The members of the Task Force have provided disclosure statements of all relationships that might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at European Heart House, headquarters of the ESC. Any changes in conflict of interest that arose during the writing period were notified to the ESC. The Task Force report received its entire financial support from the ESC and EACTS, without any involvement of the pharmaceutical, device, or surgical industry. ESC …

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

### Abbreviations 1st AV : First-degree atrioventricular block AF : atrial fibrillation AT : atrial tachyarrhythmia ATP : Anti-tachycardia pacing AV : atrioventricular BBB : bundle branch block CHF : congestive heart failure CI : confidence interval CPG : Committee for Practice Guidelines CRT : cardiac resynchronization therapy CRT-D : cardiac resynchronization therapy and defibrillator CRT-P : cardiac resynchronization therapy and pacemaker ECG : electrocardiogram EDMD : Emery-Dreifuss muscular dystrophy EF : ejection fraction EPS : electrophysiological study ESC : European Society of Cardiology HCM : hypertrophic cardiomyopathy HF : heart failure HR : hazard ratio HV : His-ventricular ICD : implantable cardioverter defibrillator ILR : implantable loop recorder IVCD : intraventricular conduction delay LBBB : left bundle branch block LQTS : long QT syndrome LV : left ventricular LVEF : left ventricular ejection fraction LVSD : left ventricular systolic dysfunction MR : mitral regurgitation MRI : magnetic resonance imaging NYHA : New York Heart Association PM : pacemaker OR : odds ratio QALY : quality-adjusted life year RBBB : right bundle branch block RCT : randomized controlled trial RV : right ventricular SB : sinus bradycardia SNRT : sinus node recovery time SR : sinus rhythm SSS : sick sinus syndrome TAVI : transcatheter aortic valve implantation VF : ventricular fibrillation VT : ventricular tachycardia VV : interventricular (delay) ### Acronyms of the trials referenced in the recommendations or reported in the tables ADEPT : ADvanced Elements of Pacing Randomized Controlled Trial ADOPT : Atrial Dynamic Overdrive Pacing Trial AOPS : Atrial Overdrive Pacing Study APAF : Ablate and Pace in Atrial Fibrillation ASSERT : ASymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial ATTEST : ATrial Therapy Efficacy and Safety Trial AVAIL CLS/CRT : AV Node Ablation with CLS and CRT Pacing Therapies for Treatment of AF trial B4 : Bradycardia detection in Bundle Branch Block BELIEVE : Bi vs. Left Ventricular Pacing: an International Pilot Evaluation on Heart Failure Patients with Ventricular Arrhythmias BIOPACE : Biventricular pacing for atrioventricular block to prevent cardiac desynchronization BLOCK-HF : Biventricular versus right ventricular pacing in patients with AV block B-LEFT : Biventricular versus LEFT Univentricular Pacing with ICD Back-up in Heart Failure Patients CARE-HF : CArdiac REsynchronization in Heart Failure CLEAR : CLinical Evaluation on Advanced Resynchronization COMBAT : COnventional vs. Biventricular Pacing in Heart Failure and Bradyarrhythmia COMPANION : COmparison of Medical Therapy, Pacing and Defibrillation in Heart Failure DANPACE : DANish Multicenter Randomized Trial on Single Lead Atrial PACing vs. Dual Chamber Pacing in Sick Sinus Syndrome DECREASE-HF : The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure FREEDOM : Optimization Study Using the QuickOpt Method GREATER-EARTH : Evaluation of Resynchronization Therapy for Heart Failure in Patients with a QRS Duration GREATER Than 120 ms LESSER-EARTH : Evaluation of Resynchronization Therapy for Heart Failure in Patients with a QRS Duration Lower Than 120 ms HOBIPACE : HOmburg BIventricular PACing Evaluation IN-CHF : Italian Network on Congestive Heart Failure ISSUE : International Study on Syncope of Unexplained Etiology MADIT : Multicenter Automatic Defibrillator Trial MIRACLE : Multicenter InSync RAndomized CLinical Evaluation MOST : MOde Selection Trial in Sinus-Node Dysfunction MUSTIC : MUltisite STimulation In Cardiomyopathies OPSITE : Optimal Pacing SITE PACE : Pacing to Avoid Cardiac Enlargement PAVE : Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation PATH-CHF : PAcing THerapies in Congestive Heart Failure II Study Group PIPAF : Pacing In Prevention of Atrial Fibrillation Study PIRAT : Prevention of Immediate Reinitiation of Atrial Tachyarrhythmias POT : Prevention Or Termination Study PREVENT-HF : PREventing VENTricular Dysfunction in Pacemaker Patients Without Advanced Heart Failure PROSPECT : PRedictors Of Response to Cardiac Resynchronization Therapy RAFT : Resynchronization–Defibrillation for Ambulatory Heart Failure Trial RethinQ : Cardiac REsynchronization THerapy IN Patients with Heart Failure and Narrow QRS REVERSE : REsynchronization reVErses Remodelling in Systolic left vEntricular dysfunction SAFARI : Study of Atrial Fibrillation Reduction SCD HeFT : Sudden Cardiac Death in Heart Failure Trial SMART-AV : The SMARTDelay Determined AV Optimization: a Comparison with Other AV Delay Methods Used in Cardiac Resynchronization Therapy SYDIT : The SYncope DIagnosis and Treatment SYNPACE : Vasovagal SYNcope and PACing TARGET : TARgeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy THEOPACE : Effects of Oral THEOphylline and of Permanent PACEmaker on the Symptoms and Complications of Sick Sinus Syndrome VASIS-PM : VAsovagal Syncope International Study on PaceMaker therapy V-HeFT : Vasodilator in HEart Failure Trial VPSII : Second Vasovagal Pacemaker Study (VPS II) Additional references are mentioned with ‘w’ in the main text and can be found on the online addenda along with 5 figures (1, 6, 7, 9, 11, 12) and 10 tables (3, 4, 5, 9, 11, 12, 19, 21, 22, 23). They are available on the ESC website only at http://www.escardio.org/guidelines-surveys/esc-guidelines/Pages/cardiac-pacing-and-cardiac-resynchronisation-therapy.aspx Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a …

Background— Data from single-center studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronization therapy (CRT). In a prospective, multicenter setting, the Predictors of Response to CRT (PROSPECT) study tested the performance of these parameters to predict CRT response. Methods and Results— Fifty-three centers in Europe, Hong Kong, and the United States enrolled 498 patients with standard CRT indications (New York Heart Association class III or IV heart failure, left ventricular ejection fraction ≤35%, QRS ≥130 ms, stable medical regimen). Twelve echocardiographic parameters of dyssynchrony, based on both conventional and tissue Doppler–based methods, were evaluated after site training in acquisition methods and blinded core laboratory analysis. Indicators of positive CRT response were improved clinical composite score and ≥15% reduction in left ventricular end-systolic volume at 6 months. Clinical composite score was improved in 69% of 426 patients, whereas left ventricular end-systolic volume decreased ≥15% in 56% of 286 patients with paired data. The ability of the 12 echocardiographic parameters to predict clinical composite score response varied widely, with sensitivity ranging from 6% to 74% and specificity ranging from 35% to 91%; for predicting left ventricular end-systolic volume response, sensitivity ranged from 9% to 77% and specificity from 31% to 93%. For all the parameters, the area under the receiver-operating characteristics curve for positive clinical or volume response to CRT was ≤0.62. There was large variability in the analysis of the dyssynchrony parameters. Conclusion— Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis, no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines. Efforts aimed at reducing variability arising from technical and interpretative factors may improve the predictive power of these echocardiographic parameters in a broad clinical setting.

Non-thrombotic PE does not represent a distinct clinical syndrome. It may be due to a variety of embolic materials and result in a wide spectrum of clinical presentations, making the diagnosis difficult. With the exception of severe air and fat embolism, the haemodynamic consequences of non-thrombotic emboli are usually mild. Treatment is mostly supportive but may differ according to the type of embolic material and clinical severity.

The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written.Health professionals are encouraged to take them fully into account when exercising their clinical judgement.The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient's guardian or carer.It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

Table 1. Classes of recommendation Table 2. Levels of evidence Table 3. Estimated fetal and maternal effective doses for various diagnostic and interventional radiology procedures Table 4. Predictors of maternal cardiovascular events and risk score from the CARPREG study Table 5. Predictors of maternal cardiovascular events identified in congential heart diseases in the ZAHARA and Khairy study Table 6. Modified WHO classification of maternal cardiovascular risk: principles Table 7. Modified WHO classification of maternal cardiovascular risk: application Table 8. Maternal predictors of neonatal events in women with heart disease Table 9. General recommendations Table 10. Recommendations for the management of congenital heart disease Table 11. Recommendations for the management of aortic disease Table 12. Recommendations for the management of valvular heart disease Table 13. Recommendations for the management of coronary artery disease Table 14. Recommendations for the management of cardiomyopathies and heart failure Table 15. Recommendations for the management of arrhythmias Table 16. Recommendations for the management of hypertension Table 17. Check list for risk factors for venous thrombo-embolism Table 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancy Table 19. Risk groups according to risk factors: definition and preventive measures Table 20. Recommendations for the prevention and management of venous thrombo-embolism in pregnancy and puerperium Table 21. Recommendations for drug use ABPM : ambulatory blood pressure monitoring ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AHA : American Heart Association aPTT : activated partial thromboplastin time ARB : angiotensin receptor blocker AS : aortic stenosis ASD : atrial septal defect AV : atrioventricular AVSD : atrioventricular septal defect BMI : body mass index BNP : B-type natriuretic peptide BP : blood pressure CDC : Centers for Disease Control CHADS : congestive heart failure, hypertension, age (>75 years), diabetes, stroke CI : confidence interval CO : cardiac output CoA : coarction of the aorta CT : computed tomography CVD : cardiovascular disease DBP : diastolic blood pressure DCM : dilated cardiomyopathy DVT : deep venous thrombosis ECG : electrocardiogram EF : ejection fraction ESC : European Society of Cardiology ESH : European Society of Hypertension ESICM : European Society of Intensive Care Medicine FDA : Food and Drug Administration HCM : hypertrophic cardiomyopathy ICD : implantable cardioverter-defibrillator INR : international normalized ratio i.v. : intravenous LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction LVOTO : left ventricular outflow tract obstruction MRI : magnetic resonance imaging MS : mitral stenosis NT-proBNP : N-terminal pro B-type natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulant PAH : pulmonary arterial hypertension PAP : pulmonary artery pressure PCI : percutaneous coronary intervention PPCM : peripartum cardiomyopathy PS : pulmonary valve stenosis RV : right ventricular SBP : systolic blood pressure SVT : supraventricular tachycardia TGA : complete transposition of the great arteries TR : tricuspid regurgitation UFH : unfractionated heparin VSD : ventricular septal defect VT : ventricular tachycardia VTE : venous thrombo-embolism WHO : World Health Organization Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the …

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

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Mutations that disrupt the open reading frame and prevent full translation of DMD, the gene that encodes dystrophin, underlie the fatal X-linked disease Duchenne muscular dystrophy. Oligonucleotides targeted to splicing elements (splice switching oligonucleotides) in DMD pre-mRNA can lead to exon skipping, restoration of the open reading frame, and the production of functional dystrophin in vitro and in vivo, which could benefit patients with this disorder.We did a single-blind, placebo-controlled, dose-escalation study in patients with DMD recruited nationally, to assess the safety and biochemical efficacy of an intramuscular morpholino splice-switching oligonucleotide (AVI-4658) that skips exon 51 in dystrophin mRNA. Seven patients with Duchenne muscular dystrophy with deletions in the open reading frame of DMD that are responsive to exon 51 skipping were selected on the basis of the preservation of their extensor digitorum brevis (EDB) muscle seen on MRI and the response of cultured fibroblasts from a skin biopsy to AVI-4658. AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. Muscles were biopsied between 3 and 4 weeks after injection. The primary endpoint was the safety of AVI-4658 and the secondary endpoint was its biochemical efficacy. This trial is registered, number NCT00159250.Two patients received 0.09 mg AVI-4658 in 900 microL (0.9%) saline and five patients received 0.9 mg AVI-4658 in 900 microL saline. No adverse events related to AVI-4658 administration were reported. Intramuscular injection of the higher-dose of AVI-4658 resulted in increased dystrophin expression in all treated EDB muscles, although the results of the immunostaining of EDB-treated muscle for dystrophin were not uniform. In the areas of the immunostained sections that were adjacent to the needle track through which AVI-4658 was given, 44-79% of myofibres had increased expression of dystrophin. In randomly chosen sections of treated EDB muscles, the mean intensity of dystrophin staining ranged from 22% to 32% of the mean intensity of dystrophin in healthy control muscles (mean 26.4%), and the mean intensity was 17% (range 11-21%) greater than the intensity in the contralateral saline-treated muscle (one-sample paired t test p=0.002). In the dystrophin-positive fibres, the intensity of dystrophin staining was up to 42% of that in healthy muscle. We showed expression of dystrophin at the expected molecular weight in the AVI-4658-treated muscle by immunoblot.Intramuscular AVI-4658 was safe and induced the expression of dystrophin locally within treated muscles. This proof-of-concept study has led to an ongoing systemic clinical trial of AVI-4658 in patients with DMD.UK Department of Health.

Stress echocardiography is the combination of 2D echocardiography with a physical, pharmacological or electrical stress. The diagnostic end point for the detection of myocardial ischemia is the induction of a transient worsening in regional function during stress. Stress echocardiography provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion imaging, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician. Among different stresses of comparable diagnostic and prognostic accuracy, semisupine exercise is the most used, dobutamine the best test for viability, and dipyridamole the safest and simplest pharmacological stress and the most suitable for combined wall motion coronary flow reserve assessment. The additional clinical benefit of myocardial perfusion contrast echocardiography and myocardial velocity imaging has been inconsistent to date, whereas the potential of adding – coronary flow reserve evaluation of left anterior descending coronary artery by transthoracic Doppler echocardiography adds another potentially important dimension to stress echocardiography. New emerging fields of application taking advantage from the versatility of the technique are Doppler stress echo in valvular heart disease and in dilated cardiomyopathy. In spite of its dependence upon operator's training, stress echocardiography is today the best (most cost-effective and risk-effective) possible imaging choice to achieve the still elusive target of sustainable cardiac imaging in the field of noninvasive diagnosis of coronary artery disease.

Proinflammatory cytokines released by injured endothelium facilitate interaction of endothelial cells with circulating leukocytes and thus may contribute to development and progression of atherosclerosis. We investigated whether cytokines and C-reactive protein (CRP) are indicative of myocardial ischemia or of diseased vessels and whether they are influenced by aspirin treatment in patients with chronic stable angina.Plasma macrophage colony stimulating factor (MCSF), IL-1b, IL-6, and CRP were measured in 60 stable patients after 48-hour Holter monitoring and in 24 matched controls. All patients had angiographic documentation of disease and positive exercise ECGs. Patients with ischemia on Holter monitoring (n=40) received aspirin or placebo in a 6-week, randomized, double blind, crossover trial. Blood sampling was repeated at the end of each treatment phase (3 weeks). Compared to controls, patients had more than twice median MCSF (800 versus 372 pg/mL), IL-6 (3.9 versus 1.7 pg/mL), and CRP (1.25 versus 0.23 mg/L) levels (P<0.01 for all comparisons). MCSF was related to ischemia on Holter monitoring (P<0.01), to low ischemic threshold during exercise (P<0.01), and together with IL-1b to number of diseased vessels (P<0.05). MCSF, IL-6, and CRP were all reduced after 6 weeks of aspirin treatment (P<0.05).These findings suggest that cytokines are associated with both ischemia and anatomic extent of disease in patients with stable angina. Reduced cytokine and CRP levels by aspirin may explain part of aspirin's therapeutic action.

Often overlooked, and considered the poor relation of the left ventricle, there is increasing interest in the right ventricle particularly with regard to right ventricular failure. Right ventricular function may be impaired as a result of pressure or volume overload, often secondary to right heart valve or muscle pathology. Coronary artery disease may also lead to right ventricular dysfunction when the right coronary artery is occluded. In congenital heart malformations the right ventricle may also be affected, particularly in conditions that have the right ventricle supporting the systemic circulation or it becomes the sole pumping chamber following univentricular repair at surgery. Finally, right-to-left shunting may lead to right ventricular dilatation. Imaging the right ventricle by echocardiography is challenging because of the very particular crescentic shape of the right ventricle wrapping around the left ventricle, but it is important and ought to be part of the standard echocardiographic examination of the heart. To help understand cross sectional imaging of the right ventricle, we first review its location and its component parts, including the tricuspid and pulmonary valves, before discussing echo-anatomic correlations. The right ventricle in the normal heart is the most anteriorly situated cardiac chamber since it is located immediately behind the sternum. It also marks the inferior border of the cardiac silhouette. In contrast to the near conical shape of the left ventricle, the right ventricle is more triangular in shape when viewed from the front and it curves over the left ventricle. When seen from the apex, the right edge of the right ventricle is sharp, forming the acute margin of the heart. In cross section the cavity appears like a crescent. Thus, the curvature of the ventricular septum places the right ventricular outflow tract antero-cephalad to that of the left ventricle’s resulting in a characteristic “cross over” relationship …

Our aim was to study the clinical characteristics and evolution of symptoms and left ventricular function in a clinically homogeneous group of patients with syndrome X (angina pectoris, positive exercise test results and normal coronary arteriograms).The syndrome of angina with normal coronary arteriograms is heterogeneous and encompasses different pathogenetic entities. These characteristics may contribute to the existing controversy concerning the cause of syndrome X.We studied 99 patients with syndrome X (78 women, 21 men; mean age +/- SD 48.5 +/- 8 years). All underwent clinical characterization, ambulatory electrocardiographic (ECG) monitoring and echocardiographic assessment of left ventricular function during a follow-up period of 7 +/- 4 years.The syndrome was more common in women than in men. Of the women, 61.5% were postmenopausal before the onset of chest pain. All 99 patients had exertional angina, and 41 also had rest angina. The average duration of episodes of chest pain was > 10 min in 53% of patients. Sublingual nitrate was effective for relief of pain in 42% of patients. Transient ST segment depression was observed during ambulatory ECG monitoring in 64 patients and myocardial perfusion abnormalities in 22. During the first stage of the exercise test, 32 patients had an increase > 20 mm Hg in systolic blood pressure and showed an earlier onset of ST depression and shorter exercise time than did patients whose blood pressure increased < or = 20%. During follow-up, no deaths or myocardial infarctions occurred, ventricular function was unchanged (shortening fraction 35.4 +/- 4% vs. 35.6 +/- 3%; heart failure developed in only one patient), systemic hypertension occurred in eight patients and conduction disturbances in four. Symptoms lessened in 11 patients, were variable or unchanged in 64 and worsened in 24.Syndrome X, as defined in this study, occurs predominantly in postmenopausal women. Patients usually have chest pain typical for angina, but conventional antianginal treatment is not often successful. Myocardial perfusion abnormalities occur in a small proportion of patients. Long-term survival is not adversely affected, and deterioration of cardiac function rarely occurs.

Cardiac resynchronization therapy (CRT) has been used extensively over the last years in the therapeutic management of patients with end-stage heart failure. Data from 4,017 patients have been published in eight large, randomized trials on CRT. Improvement in clinical end points (symptoms, exercise capacity, quality of life) and echocardiographic end points (systolic function, left ventricular size, mitral regurgitation) have been reported after CRT, with a reduction in hospitalizations for decompensated heart failure and an improvement in survival. However, individual results vary, and 20% to 30% of patients do not respond to CRT. At present, the selection criteria include severe heart failure (New York Heart Association functional class III or IV), left ventricular ejection fraction <35%, and wide QRS complex (>120 ms). Assessment of inter- and particularly intraventricular dyssynchrony as provided by echocardiography (predominantly tissue Doppler imaging techniques) may allow improved identification of potential responders to CRT. In this review a summary of the clinical and echocardiographic results of the large, randomized trials is provided, followed by an extensive overview on the currently available echocardiographic techniques for assessment of LV dyssynchrony. In addition, the value of LV scar tissue and venous anatomy for the selection of potential candidates for CRT are discussed.

The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention (PCI) with stenting against coronary artery bypass grafting (CABG) in patients with diabetes and symptomatic multivessel coronary artery disease.CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease, but with advances in PCI, there is uncertainty whether CABG remains the preferred method of revascularization.The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke, and the main secondary outcome included the addition of repeat revascularization to the primary outcome events. A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were randomized to PCI plus stenting (and routine abciximab) or CABG. The primary comparison used a noninferiority method with the upper boundary of the 95% confidence interval (CI) not to exceed 1.3 to declare PCI noninferior. Bare-metal stents were used initially, but a switch to Cypher (sirolimus drug-eluting) stents (Cordis, Johnson & Johnson, Bridgewater, New Jersey) was made when these became available.At 1 year of follow-up, the composite rate of death, MI, and stroke was 10.5% in the CABG group and 13.0% in the PCI group (hazard ratio [HR]: 1.25, 95% CI: 0.75 to 2.09; p=0.39), all-cause mortality rates were 3.2% and 3.2%, and the rates of death, MI, stroke, or repeat revascularization were 11.3% and 19.3% (HR: 1.77, 95% CI: 1.11 to 2.82; p=0.02), respectively. When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents (69% of patients), the primary outcome rates were 12.4% and 11.6% (HR: 0.93, 95% CI: 0.51 to 1.71; p=0.82), respectively.The CARDia (Coronary Artery Revascularization in Diabetes) trial is the first randomized trial of coronary revascularization in diabetic patients, but the 1-year results did not show that PCI is noninferior to CABG. However, the CARDia trial did show that multivessel PCI is feasible in patients with diabetes, but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies. (The Coronary Artery Revascularisation in Diabetes trial; ISRCTN19872154).

This study was conducted to investigate the presentation and outcome of patients with Ebstein's anomaly of the tricuspid valve.Ebstin's anomaly may present at any age and has a highly variable clinical course. Previous natural history studies have been based on clinical and angiographic diagnosis and have included mainly older children and adults. Echocardiography, however, has facilitated fetal and neonatal diagnosis so that the natural history needs to be redefined.We reviewed 220 cases of Ebstein's anomaly presenting from fetal to adult life between 1958 and 1991, with 1 to 34 years of follow-up.The most common presentation in each age group was abnormal routine prenatal scan for fetuses (86%), cyanosis for neonates (74%), heart failure for infants (43%), incidental murmur for children (63%) and arrhythmia for adolescents and adults (42%). Early presentation was frequently associated with other cardiac lesions, usually pulmonary stenosis or atresia. Surgery was undertaken at some stage in 86 (39%) of the 220 patients. Actuarial survival for all liveborn patients was 67% at 1 year and 59% at 10 years. There were 58 deaths, including 26 from heart failure, 19 perioperative and 8 sudden. Predictors of death included echocardiographic grade of severity at presentation (relative risk 2.7 for each increase in grade, 95% confidence limits 1.6 to 4.6), fetal presentation (6.9, confidence limits 1.6 to 16.5) and right ventricular outflow tract obstruction (2.1, confidence limits 1.1 to 4.4). Morbidity was mainly related to arrhythmias and late hemodynamic deterioration. Of 155 survivors, 129 (83%) were in functional class 1 and 104 (67%) were receiving no medical therapy.In Ebstein's anomaly, fetal and neonatal presentation is associated with a poor outcome and can be predicted by the echocardiographic appearance and presence of associated lesions. In older children and adults, incidental findings and arrhythmia are common and the long-term outcome is superior.

Echocardiography plays an important role in the diagnosis and follow-up of aortic diseases. Evaluation of the aorta is a routine part of the standard echocardiographic examination. Transthoracic echocardiography (TTE) permits adequate assessment of several aortic segments, particularly the aortic root and proximal ascending aorta. Transoesophageal echocardiography (TOE) overcomes the limitations of TTE in thoracic aorta assessment. TTE and TOE should be used in a complementary manner. Echocardiography is useful for assessing aortic size, biophysical properties, and atherosclerotic involvement of the thoracic aorta. Although TOE is the technique of choice in the diagnosis of aortic dissection, TTE may be used as the initial modality in the emergency setting. Intimal flap in proximal ascending aorta, pericardial effusion/tamponade, and left ventricular function can be easily visualized by TTE. However, a negative TTE does not rule out aortic dissection and other imaging techniques must be considered. TOE should define entry tear location, mechanisms and severity of aortic regurgitation, and true lumen compression. In addition, echocardiography is essential in selecting and monitoring surgical and endovascular treatment and in detecting possible complications. Although other imaging techniques such as computed tomography and magnetic resonance have a greater field of view and may yield complementary information, echocardiography is portable, rapid, accurate, and cost-effective in the diagnosis and follow-up of most aortic diseases.

Cardiac resynchronization therapy (CRT) has been proposed as an alternative treatment in patients with severe, drug-refractory heart failure. The clinical results are promising, and improvement in symptoms, exercise capacity, and systolic left ventricular (LV) function have been demonstrated after CRT, accompanied by a reduction in hospitalization and a superior survival as compared with optimized medical therapy alone. However, 20% to 30% of patients do not respond to CRT. Currently, patients are selected mainly on electrocardiogram criteria (wide QRS complex, left bundle branch block configuration). In view of the 20% to 30% of nonresponders, additional selection criteria are needed. Echocardiography (and, in particular, tissue Doppler imaging) may allow further identification of potential responders to CRT, based on assessment of inter- and intraventricular dyssynchrony. In addition, echocardiography may allow optimal LV lead positioning and follow-up after CRT. In the current review, the different echocardiographic approaches to predict response to CRT are discussed. In addition, the use of echocardiography to guide LV lead positioning and follow-up after CRT are addressed.

Rationale: Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the treatment for pulmonary arterial hypertension (PAH). Objective: This study compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the current practice of adding bosentan, an endothelin receptor antagonist. Methods: Twenty-six patients with PAH, idiopathic or associated with connective tissue disease, World Health Organization (WHO) functional class III, were randomized in a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) over 16 weeks. Measurements: Changes in right ventricular (RV) mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac function, brain natriuretic peptide, and Borg dyspnea index. Main Results: When analyzed by intention to treat, there were no significant differences between the two treatment groups. One patient on sildenafil died suddenly. Patients on sildenafil who completed the protocol showed significant changes from baseline, namely, reductions in RV mass (−8.8 g; 95% confidence interval [CI], −2, −16; n = 13, p = 0.015) and plasma brain natriuretic peptide levels (−19.4 fmol · ml−1; 95% CI, −5, −34; p = 0.014) and improvements in 6-minute walk distance (114 m; 95% CI, 67, 160; p = 0.0002), cardiac index (0.3 L · min−1 · m−2; 95% CI, 0.1, 0.4; p = 0.008), and systolic left ventricular eccentricity index (−0.2; 95% CI, −0.02, −0.37; p = 0.031). Bosentan improved 6-minute walk distance (59 m; 95% CI, 29, 89; n = 12, p = 0.001) and cardiac index (0.3; 95% CI, 0.1, 0.4; p = 0.008). Conclusions: Sildenafil added to conventional treatment reduces RV mass and improves cardiac function and exercise capacity in patients with PAH, WHO functional class III. Safety monitoring is important until more experience is obtained.

In view of the European Association of Echocardiography (EAE) mission statement “To promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular ultrasound in Europe” and the increasing demand for standardization and quality control, the EAE have established recommendations and guidelines for standardization of echocardiography performance, data acquisition (images, measurements and morphologic descriptors), digital storage and reporting of echocardiographic studies. The aim of these recommendations is to provide a European consensus document on the minimum acceptable requirements for the clinical practice of echocardiography today and thus improve the quality and consistency of echocardiographic practice in Europe.

In studies of the right ventricle the complexities of chamber shape may be overcome by use of multiple tomographic imaging planes. An established protocol for the echocardiographic description of the heart was used to examine the right ventricle in an ordered series of transducer locations and orientations. Diastolic measurements were made of the right ventricular inflow tract, outflow tract, and right ventricular body, and the range and reproducibility of normal values for cavity size and right ventricular free wall thickness were established. These measurements of cavity size in 41 normal subjects were highly reproducible and the views that were used correctly described the truncated and ellipsoidal shape of the right ventricular inflow tract and body with a separately aligned outflow tract. Cavity trabeculation prevented measurement of the free wall thickness in some areas; however, values of nearly twice the previously reported upper limit of normal for anterior regions were measured from the apex or lateral right ventricular wall. These normal data provide a basis for future echocardiographic studies of the right ventricle.

This paper examines the evidence for contrast echocardiography, both for improving assessment of left ventricular structure and function compared with unenhanced echocardiography and for the identification of myocardial perfusion. Based on the evidence, recommendations are proposed for the clinical use of contrast echocardiography.

Stress echocardiography is the combination of echocardiography with a physical, pharmacological, or electrical stress. The diagnostic endpoint for the detection of myocardial ischaemia is the induction of a transient worsening in regional function during stress. Stress echocardiography provides similar diagnostic and prognostic accuracy to radionuclide stress perfusion imaging, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician. Among different stresses of comparable diagnostic and prognostic accuracy, semisupine exercise is the most used, dobutamine the best test for viability, and dipyridamole the safest and simplest pharmacological stress and the most suitable for combined wall motion coronary flow reserve assessment. The additional clinical benefit of myocardial perfusion contrast echocardiography and myocardial velocity imaging has been inconsistent to date, whereas the possibility of performing coronary flow reserve evaluation of the left anterior descending coronary artery by transthoracic Doppler echocardiography adds another potentially important dimension to stress echocardiography. New emerging fields of application taking advantage of the versatility of the technique are Doppler stress echo in valvular heart disease and in dilated cardiomyopathy. In spite of its dependence on the operator's training, stress echocardiography is today the best (most cost-effective and risk-effective) possible imaging choice to achieve the still elusive target of sustainable cardiac imaging in the field of non-invasive diagnosis of coronary artery disease. In 1935, Tennant and Wiggers1 demonstrated that coronary occlusion immediately resulted in instantaneous abnormality of wall motion. A large body of evidence2–5 recognized for the first time that transient dys-synergy was an early, sensitive, specific marker of transient ischaemia, clearly more accurate than ECG changes and pain. In European clinical practice,6–10 stress echo has been embedded in the legal and cultural framework of existing European laws and medical imaging referral guidelines. The …

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing trans-catheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease. The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing trans-catheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease. Attention ASE Members:ASE has gone green! Visit www.aseuniversity.org to earn free continuing medical education credit through an online activity related to this article. Certificates are available for immediate access upon successful completion of the activity. Nonmembers will need to join the ASE to access this great member benefit!

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease.

Embolism of cardiac origin accounts for around 15-30% of ischaemic strokes. Strokes due to cardioembolism are generally severe and early and long-term recurrence and mortality are high. The diagnosis of a cardioembolic source of stroke is frequently uncertain and relies on the identification of a potential cardiac source of embolism in the absence of significant autochthone cerebrovascular occlusive disease. In this respect, echocardiography (both transthoracic and/or transoesophageal) serves as a cornerstone in the evaluation, diagnosis, and management of these patients. A clear understanding of the various types of cardiac conditions associated with cardioembolic stroke and their intrinsic risk is therefore very important. This article reviews potential cardiac sources of embolism and discusses the role of echocardiography in clinical practice. Recommendations for the use of echocardiography in the diagnosis of cardiac sources of embolism are given including major and minor conditions associated with the risk of embolism.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio‐Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio‐Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio‐oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three‐dimensional ejection fraction, are proposed. The protocol for baseline pre‐treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2‐targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr‐Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio‐oncology are discussed.

Ventricular–arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non‐invasive measurement of the ratio of arterial (Ea) to ventricular end‐systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo–arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.

The Dietary Approaches to Stop Hypertension (DASH) diet is recognized as an effective dietary intervention to reduce blood pressure (BP). However, among randomized controlled trials (RCTs) investigating the DASH diet-mediated BP reduction, there are significant methodological and clinical differences. The purpose of this study was to comprehensively assess the DASH diet effect on BP in adults with and without hypertension, accounting for underlying methodological and clinical confounders. We systematically searched Medline and the Cochrane Collaboration Library databases and identified 30 RCTs (n = 5545 participants) that investigated the BP effects of the DASH diet compared with a control diet in hypertensive and nonhypertensive adults. Both random-effects and fixed-effect models were used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted. Compared with a control diet, the DASH diet reduced both SBP and DBP (difference in means: -3.2 mm Hg; 95% CI: -4.2, -2.3 mm Hg; P < 0.001, and -2.5 mm Hg; 95% CI: -3.5, -1.5 mm Hg; P < 0.001, respectively). Hypertension status did not modify the effect on BP reduction. The DASH diet compared with a control diet reduced SBP levels to a higher extent in trials with sodium intake >2400 mg/d than in trials with sodium intake ≤2400 mg/d, whereas both SBP and DBP were reduced more in trials with mean age <50 y than in trials of older participants. The quality of evidence was rated as moderate for both outcomes according to the Grading of Recommendations, Assessment, Development, and Evaluation approach. The adoption of the DASH diet was accompanied by significant BP reduction in adults with and without hypertension, although higher daily sodium intake and younger age enhanced the BP-lowering effect of the intervention. This meta-analysis was registered at www.crd.york.ac.uk/prospero as CRD42019128120.

Abstract Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as ‘HFrEF’ (HF with reduced LVEF), ‘HFpEF’ (HF with preserved LVEF), and more recently ‘HFmrEF’ (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone.

Abstract Pulmonary hypertension is defined as a mean arterial pressure of ≥25 mmHg as confirmed on right heart catheterisation. Traditionally, the pulmonary arterial systolic pressure has been estimated on echo by utilising the simplified Bernoulli equation from the peak tricuspid regurgitant velocity and adding this to an estimate of right atrial pressure. Previous studies have demonstrated a correlation between this estimate of pulmonary arterial systolic pressure and that obtained from invasive measurement across a cohort of patients. However, for an individual patient significant overestimation and underestimation can occur and the levels of agreement between the two is poor. Recent guidance has suggested that echocardiographic assessment of pulmonary hypertension should be limited to determining the probability of pulmonary hypertension being present rather than estimating the pulmonary artery pressure. In those patients in whom the presence of pulmonary hypertension requires confirmation, this should be done with right heart catheterisation when indicated. This guideline protocol from the British Society of Echocardiography aims to outline a practical approach to assessing the probability of pulmonary hypertension using echocardiography and should be used in conjunction with the previously published minimum dataset for a standard transthoracic echocardiogram.

While patient history taking and physical examination remain the cornerstones of patient evaluation in clinical practice, there has been a decline in the accuracy of the latter. Pocket-size hand-held echocardiographic (PHHE) devices have recently been introduced and could potentially improve the diagnostic accuracy of both medical students and junior doctors. The amount of training required to achieve optimal results remains a matter of debate. We hypothesized that the use of PHHE after limited training in the form of a tutorial can improve the clinical diagnosis even in the hands of medical students and inexperienced physicians.Five final-year medical students and three junior doctors without prior echocardiographic experience participated in a standardized 2 h PHHE bedside tutorial. Subsequently, they assessed 122 cardiology patients using history, physical examination, ECG and PHHE. Their final clinical diagnosis was compared against that of a consultant clinician's and also expert in echocardiography. A total of 122 PHHE were performed of which 64 (53%) by final-year medical students and 58 (47%) by junior doctors. Mean ± SD for diagnostic accuracy after history, physical examination, and ECG interpretation was 0.49 ± 0.22 (maximum = 1), whereas the addition of PHHE increased its value to 0.75 ± 0.28 (Z = -7.761, P<0.001). When assessing left ventricular systolic dysfunction by means of history and physical examination, specificity was 84.9% and sensitivity only 25.9%, whereas after including findings from PHHE, these figures rose to 93.6 and 74.1%, respectively.The use of PHHE after brief bedside training in the form of a tutorial greatly improved the clinical diagnosis of medical students and junior doctors, over and above history, physical examination, and ECG findings.

ACC/AHA : American College of Cardiology/American Heart Association ACCF/AHA : American College of Cardiology Foundation/American Heart Association ACE : angiotensin-converting enzyme ACEI : angiotensin-converting enzyme inhibitor ACS : acute coronary syndrome AF : atrial fibrillation

Quantitative assessment of right ventricular (RV) systolic function largely depends on right ventricular ejection fraction (RVEF). Three-dimensional speckle tracking (3D-ST) has been used extensively to quantify left ventricular function, but its value for RV assessment has not been established. This study sought to prospectively assess whether 3D-ST would be a reliable method for assessing RV systolic function and whether strain values were associated with survival. Comprehensive 2-dimensional echocardiographic assessment, 3D-ST of the RV free wall, and measurement of RVEF was performed in 97 consecutive patients with established pulmonary hypertension (PHT) (RVEF 31.4 ± 9.6%, right ventricular systolic pressure [RVSP] 76.5 ± 26.2 mm Hg) and 60 healthy volunteers (RVEF 43.8 ± 9.4%, RVSP 25.9 ± 4.3 mm Hg). Area strain (AS) (−24.3 ± 7.3 vs. −30.8 ± 7.2; p < 0.001), radial strain (23.2 ± 14.4 vs. 34.9 ± 18.2; p < 0.001), longitudinal strain (LS) (−15.5 ± 3.8 vs. −17.9 ± 4.4; p = 0.001), and circumferential strain (CS) (−12.2 ± 4.5 vs. −15.7 ± 6.1; p < 0.001) were all reduced in patients with PHT, compared with normal individuals. AS and CS strongly correlated to RVEF (r = 0.851, r = −0.711; p < 0.001). Systolic dyssynchrony index was greater in PHT (0.14 ± 0.06 vs. 0.11 ± 0.07; p = 0.003) and correlated to RVEF (r = −0.563, p < 0.001). AS (hazard ratio [HR]: 3.49; 95% confidence interval [CI]: 1.21 to 7.07; p = 0.017), CS (HR: 4.17; 95% CI: 1.93 to 12.97; p < 0.001), LS (HR: 7.63; 95% CI: 1.76 to 10.27; p = 0.001), and RVEF (HR: 2.43; 95 CI: 1.00 to 5.92; p = 0.050) were significant determinants of all-cause mortality. Only AS (p = 0.029) and age (p = 0.087) were predictive of death after logistic regression analysis. PHT patients have reduced RV strain patterns and more dyssynchronous ventricles compared with controls, which was relatable to clinical outcomes. AS best correlated with RVEF and provides prognostic information independent of other variables.

Contrast echocardiography is widely used in cardiology. It is applied to improve image quality, reader confidence and reproducibility both for assessing left ventricular (LV) structure and function at rest and for assessing global and regional function in stress echocardiography. The use of contrast in echocardiography has now extended beyond cardiac structure and function assessment to evaluation of perfusion both of the myocardium and of the intracardiac structures. Safety of contrast agents have now been addressed in large patient population and these studies clearly established its excellent safety profile. This document, based on clinical trials, randomized and multicentre studies and published clinical experience, has established clear recommendations for the use of contrast in various clinical conditions with evidence-based protocols.

Two-dimensional echocardiographic studies were prospectively performed in 93 patients with systemic lupus erythematosus (SLE) to discover the incidence and spectrum of cardiac abnormalities and to relate these findings to the presence of high levels of anticardiolipin antibodies. Assessment of the intracardiac anatomy was also performed in an additional 12 patients who had increased anticardiolipin antibody levels but did not have SLE. Fifty patients (54%) with SLE had cardiac abnormalities, and 43 patients (46%) had normal hearts. Three categories of cardiac abnormalities were identified--valvular lesions, ranging from vegetations to valvular thickening, were found in 28%, pericardial effusion or thickening was found in 20%, and regional or global left ventricular dysfunction was found in 5%. High levels of anticardiolipin antibodies were detected in 50 patients (54%) with SLE. Of those, only 11 (22%) had an entirely normal heart, whereas the remaining 39 (78%) had at least one cardiac abnormality (valvular lesions in 20, pericardial effusion in 15, and myocardial dysfunction in five patients). In patients with SLE, the presence of abnormal intracardiac anatomy was strongly associated with increased levels of anticardiolipin antibodies (p less than 0.0001). The overall sensitivity and specificity of high levels of anticardiolipin antibodies in the prediction of cardiac abnormalities was 78% and 74%, respectively, with a positive predictive accuracy of 78% and a negative predictive accuracy of 74%. Eight of the 12 patients (67%) who had increased anticardiolipin antibodies but whose disease did not fulfill the American Rheumatism Association classification criteria for SLE had cardiac abnormalities similar to those in patients with SLE compared with only four (33%) who had normal hearts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

In adults with hypertrophic cardiomyopathy, the annual mortality rate from sudden death is 2 to 3%, and the finding of nonsustained ventricular tachycardia during electrocardiographic (ECG) monitoring provides a marker of the patient who is at increased risk. In the young, the annual mortality rate from sudden death is even higher, approximately 6%, but the prognostic significance of arrhythmia is unknown. To determine the prevalence of arrhythmia and its relation to prognosis, 2 days of ECG monitoring was performed in 6 infants, 14 children and 33 adolescents with hypertrophic cardiomyopathy receiving no cardioactive medications. An additional 1 to 9 days (median 2) of monitoring was performed in 29 patients. All patients had sinus rhythm; 4 adolescents had episodes of paroxysmal supraventricular tachycardia, a child with the Wolff-Parkinson-White syndrome had symptomatic reentrant atrioventricular tachycardia and 5 adolescents had asymptomatic nonsustained ventricular tachycardia. During follow-up of 1 week to 7 years (median 3 years), five patients died suddenly and two had successful resuscitation from out-of-hospital ventricular fibrillation; none of these seven patients had ventricular arrhythmias during 2 to 7 days (median 3) of ECG monitoring. The two patients with ventricular fibrillation, the five with ventricular tachycardia, the one with Wolff-Parkinson-White syndrome and the seven with recurrent syncope or adverse family history, or both, received low dose amiodarone. None of these "high risk" patients died during 6 months to 6 years (median 3 years) of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

The physiological importance of the right ventricle (RV) has been underestimated; the RV was considered mainly as a conduit whereas its contractile performance was thought to be haemodynamically unimportant.1 However, its essential contribution to normal cardiac pump function is well established with the primary RV functions being: RV function may be impaired either by primary right sided heart disease, or secondary to left sided cardiomyopathy or valvar heart disease.2 In addition, it should be considered that RV dysfunction may affect left ventricular (LV) function, not only by limiting LV preload, but also by adverse systolic and diastolic interaction via the intraventricular septum and the pericardium (ventricular interdependence). Moreover, RV function has been shown to be a major determinant of clinical outcome3–9 and consequently should be considered during clinical management and treatment.10 Thus, the need for diagnosis of RV dysfunction is evident. In practice, clinicians largely rely on non-invasive imaging methods for assessment of RV function. Two dimensional echocardiography is the mainstay for analysis of RV function, but recently alternative techniques have been proposed, including tissue Doppler imaging (TDI) techniques,11 three dimensional echocardiography,12 magnetic resonance imaging (MRI), and even invasive assessment of pressure–volume loops.13–17 An overview of these imaging modalities for assessment of RV function is provided in the current manuscript. Due to its widespread availability, echocardiography is used as the first line imaging modality for assessment of RV size and RV function. The quantitative assessment of RV size and function is often difficult, because of the complex anatomy. Nevertheless, when used …

Cardiac resynchronization therapy (CRT) is currently indicated in patients with moderate to severe heart failure, a wide QRS complex and significant left ventricular dysfunction despite optimal medical therapy. Adoption of these criteria for CRT results in a favorable response in only two thirds of candidates."Predictors of response to cardiac resynchronization therapy (PROSPECT)," a prospective, multicenter, nonrandomized study, aims to identify echocardiographic measures of dyssynchrony and evaluate their ability to predict response to CRT. PROSPECT will enroll approximately 300 patients in up to 75 centers in the United States, Asia, and Europe with clinical follow-up for 6 months. We will prospectively and individually test a variety of conventional echocardiographic and tissue Doppler imaging parameters against measures of clinical response. The primary response criteria are improvement in the heart failure Clinical Composite Score and left ventricular reverse remodeling. Enrollment began in March 2004 and is expected to conclude early 2005.

To assess the incidence and natural course of paravalvular leaks detected early after aortic valve replacement.Although the use of echocardiography has simplified the postoperative assessment of patients with aortic valve replacement, there are no data regarding the natural history of early detected paravalvular aortic leaks.Eighty-four consecutive patients with aortic valve replacement were prospectively followed clinically every 6 months and by echocardiography early (11 +/- 7 days), at midterm (27 +/- 3 months), and late (63 +/- 4 months) after aortic valve replacement. The competence of artificial valves was assessed by Doppler color flow mapping.Paraprosthetic leaks were detected in 40 (47.6%) aortic prostheses during the early study; the majority (90%) were small. All leaks remained unchanged during the follow-up period. Left ventricular dimensions and function did not differ between patients with or without paravalvular leak during the follow-up. Left ventricular fractional shortening, however, increased during the intermediate study in both subgroups, indicating improved left ventricular function overall. Three patients had severe paravalvular regurgitation suddenly develop from late infective endocarditis, and 1 patient had a degenerative tissue valve failure 4 years after implantation.Paraprosthetic aortic leaks detected early after surgery, in the absence of valve infection, are common, are usually small, and have a benign course. However, the development of new, usually severe, regurgitation should raise the suspicion of prosthetic valve endocarditis or bioprosthetic valve failure.

Background. Circulating transthyretin (TTR) is derived from the liver, and orthotopic liver transplantation (OLT) is widely performed for variant TTR-associated familial amyloid polyneuropathy (FAP). The effect of OLT on FAP-related cardiac amyloid is of particular interest because wild-type TTR can itself be deposited as senile cardiac amyloid. Methods. Serial echocardiography was performed in 20 FAP patients, 14 of whom underwent OLT, and 10 other liver transplant patients. Follow-up included serum amyloid P component scintigraphy and measurement of plasma TTR before and after OLT. Results. Cardiac amyloidosis progressed rapidly in three FAP patients (TTR Pro52 and Thr84 mutations) after OLT, even though the deposits elsewhere had stabilized or regressed. Results of echocardiography improved in three transplant patients with TTR Met30 and remained normal in seven other patients. Plasma TTR levels were altered substantially after OLT, but they did not reflect the cardiac findings. Conclusions. Although amyloid deposition in FAP is generally inhibited after OLT, cardiac amyloidosis can be exacerbated, probably due to enhanced deposition of wild-type TTR on a template of amyloid derived from variant TTR. The phenomenon may be mutation-dependent. These findings suggest that amyloid formation de novo and its subsequent accumulation can be promoted by different factors, which may be organ-specific.

The main mission statement of the European Association of Echocardiography (EAE) is 'to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular ultrasound in Europe'. As competence and quality control issues are increasingly recognized by patients, physicians, and payers, the EAE has established recommendations for training, competence, and quality improvement in echocardiography. The purpose of this document is to provide the requirements for training and competence in echocardiography, to outline the principles of quality measurement, and to recommend a set of measures for improvement, with the ultimate goal of raising the standards of echocardiographic practice in Europe.

Encouraged by the clinical success of cardiac resynchronization therapy (CRT), the implantation rate has increased exponentially, although several limitations and unresolved issues of CRT have been identified. This review concerns issues that are encountered during implantation of CRT devices, including the role of electroanatomical mapping, whether CRT implantation should be accompanied by simultaneous atrioventricular nodal ablation in patients with atrial fibrillation, procedural complications, and when to consider surgical left ventricular lead positioning. Furthermore, (echocardiographic) CRT optimization and assessment of CRT benefits after implantation are highlighted. Also, controversial issues such as the potential value of CRT in patients with mild heart failure or narrow QRS complex are addressed. Finally, open questions concerning when to combine CRT with implantable cardioverter-defibrillator therapy and the cost-effectiveness of CRT are discussed.

Objective: To test whether the silence of painless myocardial ischemia is caused by abnormal handling by the central nervous system of afferent messages from the heart. Design: Nonrandomized study. Setting: A tertiary referral center (postgraduate medical school). Patients: 2 matched groups of nondiabetic patients with coronary artery disease. Group A consisted of nine patients with reproducible stress-induced angina; group B consisted of nine patients with reproducible stress-induced myocardial ischemia but no angina. Interventions: Intravenous placebo infusion and low-dose (5 and 10 µg/kg per minute) and high-dose (20 to 35 µg/kg per minute) dobutamine infusions. Measurements: Positron emission tomography was used to measure regional cerebral blood flow changes as an index of neuronal activation during painful and silent myocardial ischemia induced by intravenous dobutamine. Results: Regional cerebral blood flow changes during myocardial ischemia were compared with those during baseline conditions and during placebo infusion. During myocardial ischemia, regional cerebral blood flow increased bilaterally in the thalami and prefrontal, basal frontal, and ventral cingulate cortices in patients in group A. Both thalami were activated in group B, but cortical activation was limited to the right frontal region. A formal comparison of groups A and B showed significant differences (P < 0.01) in activation of the basal frontal cortex, ventral cingulate cortex, and left temporal pole. In both groups, thalamic regional cerebral blood flow remained increased after the symptoms and signs of ischemia had ceased. Conclusions: Bilateral activation of the thalamus can be shown in both angina and silent ischemia; thus, peripheral nerve dysfunction cannot completely explain silent ischemia. Frontal cortical activation appears to be necessary for the sensation of pain. Abnormal central processing of afferent pain messages from the heart may play a determining role in silent myocardial ischemia.

Stress two-dimensional echocardiographic studies were performed in 18 patients with angina, a positive exercise test and normal findings on coronary angiography (syndrome X). Rest and immediate posttreadmill exercise two-dimensional echocardiograms were performed with a digitized cine loop and side by side visual analysis in all patients. In 16 of these patients, right atrial pacing up to 160 beats/min was also performed and percent systolic wall thickening was calculated at five equally spaced segments around the left ventricle, each corresponding to an anterior, lateral and inferior wall and the posterior and the anterior ventricular septum. Measurements of percent systolic wall thickening were established in 10 age- and gender-matched normal persons for comparison. ST segment depression occurred in all patients during exercise and persisted for 42.1 s (range 18 to 75) into the recovery period. Immediate postexercise echocardiography was started within 20.1 ± 5.4 s and completed in 54.1 ± 11.3 s. No patient had regional wall motion abnormalities seen on two-dimensional imaging of any myocardial segment. Thirteen patients (72%) reported reproduction of their usual chest pain, which led to termination of the test. During rapid right atrial pacing, nine patients (56%) developed ST segment depression that was associated with angina in seven. In all 16 patients, percent systolic wall thickening increased over values at rest in each myocardial segment. Percent systolic wall thickening averaged 47.1 ± 6.1 % at rest and increased to 74 ± 8% during right atrial pacing (p < 0.001). Thus, patients with syndrome X have normal systolic function at rest and immediately after exercise, despite electrocardiographic ST segment depression resembling that during ischemia and effort-related angina that are clinically indistinguishable from those of patients with atherosclerotic coronary artery disease.

Two families are described in which individuals showed widespread myocardial disarray at histological examination, in the absence of macroscopic cardiac hypertrophy. In one family the clinical presentation was that of sudden unexpected cardiac death in four family members; members of the other family presented with electrocardiographic repolarisation changes and abnormalities of left ventricular diastolic function. The finding of myocardial disarray, the characteristic histological abnormality of hypertrophic cardiomyopathy, in the absence of increased cardiac mass suggests a wider range of abnormality in hypertrophic cardiomyopathy than is currently recognised.

To compare outcome in patients with medically treated secundum atrial septal defect (ASD) first diagnosed after the age of 25 with the long-term outcome in a similar group of patients after surgical closure.A historical, prospective, unrandomised study.A tertiary referral centre.All patients with ASD followed up since 1955 who fulfilled the entry criteria and had reached a current age of over 45 years--that is, 34 medical and 48 surgical patients with a mean follow up of 25 years.Survival, symptoms, and complications.There was no difference in survival or symptoms between the two groups and no difference in the incidence of new arrhythmias, stroke or other embolic phenomena, or cardiac failure. No patient in either group developed progressive pulmonary vascular disease.Outcome in adults with ASD was not improved by surgical closure. Because progressive pulmonary vascular disease did not develop in any of these patients its prevention is not a reason for advising closure of ASD in adults.

Patients with suspected pulmonary hypertension (PH) should be evaluated using a multimodality approach to ensure that they receive a correct diagnosis. The series of investigations required includes clinical evaluation, noninvasive imaging techniques and right heart catheterisation (considered to be the "gold standard" for the diagnosis of PH). Current guidelines recommend that a detailed echocardiographic assessment is performed in all patients with suspected PH. In this review we summarise a protocol adopted by the National Pulmonary Hypertension Centres of UK and Ireland and approved by the British Society of Echocardiography for the evaluation of these patients. The views and measurements described are recommended for diagnosis, assisting in prognosis and providing a noninvasive means of following disease progression or response to therapy.

Rationale: In animal models of pulmonary hypertension, simvastatin has been shown to reduce pulmonary artery pressure and induce regression of associated right ventricular (RV) hypertrophy.Objectives: To assess the therapeutic value of simvastatin in patients with pulmonary arterial hypertension (PAH).Methods: Forty-two patients with PAH were randomized to receive either simvastatin (80 mg/d) or placebo in addition to current care for 6 months, and thereafter offered open-label simvastatin.The primary outcome was change in RV mass, assessed by cardiac magnetic resonance (CMR).Measurements and Main Results: At 6 months, RV mass decreased by 5.2 6 11 g in the statin group (P 5 0.045) and increased 3.9 6 14 g in the placebo group.The treatment effect was 29.1 g (P 5 0.028).N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels decreased significantly in the statin group (275 6 167 fmol/ml; P 5 0.02) but not the placebo group (49 6 224 fmol/ml; P 5 0.43; overall treatment effect 2124 fmol/ml; P 5 0.041).There were no significant changes in other outcome measures (including 6-minute walk test, cardiac index, and circulating cytokines).From 6 to 12 months, both RV mass and NT-proBNP increased toward baseline values in 16 patients on active treatment who continued with simvastatin but remained stable in 18 patients who switched from placebo to simvastatin.Two patients required a reduction in dose but not cessation of simvastatin.Conclusions: Simvastatin added to conventional therapy produces a small and transient early reduction in RV mass and NT-proBNP levels in patients with PAH, but this is not sustained over 12 months.Clinical trial registered with www.clinicaltrials.gov(NCT00180713).

Ginsenoside Rd is an active ingredient in Panax ginseng CA Mey and can be absorbed into the adipose tissue. Adipokines play an important role in the treatment of cardiovascular diseases. However, the potential benefit of Rd on heart failure (HF) and the underlying mechanism associated with the crosstalk between adipocytes and cardiomyocytes remains to be illustrated. Here, the results identified that Rd improved cardiac function and inhibited cardiac pathological changes in transverse aortic constriction (TAC), coronary ligation (CAL) and isoproterenol (ISO)-induced HF mice. And Rd promoted the release of omentin from the adipose tissue and up-regulated omentin expression in lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes. Further, Rd could increase TBK1 and AMPK phosphorylation in adipocytes. And also, the TBK1-AMPK signaling pathway regulated the expression of omentin in LPS-induced adipocytes. Moreover, the omentin mRNA expression was significantly decreased by TBK1 knockdown in LPS-induced 3T3-L1 adipocytes. Additionally, molecular docking and SPR analysis confirmed that Rd had a certain binding ability with TBK1, and co-treatment with TBK1 inhibitors or TBK1 knockdown partially abolished the effect of Rd on increasing the omentin expression and the ratio of p-AMPK to AMPK in adipocytes. Moreover, we found that circulating omentin level diminished in the HF patients compared with healthy subjects. Meanwhile, the adipose tissue-specific overexpression of omentin improved cardiac function, reduced myocardial infarct size and ameliorated cardiac pathological features in CAL-induced HF mice. Consistently, exogenous omentin reduced mtROS levels and restored ΔψM to improve oxygen and glucose deprivation (OGD)-induced cardiomyocytes injury. Further, omentin inhibited the WNT5A/Ca2+ signaling pathway and promoted mitochondrial biogenesis function to ameliorate myocardial ischemia injury. However, WNT5A knockdown inhibited the impairment of mitochondrial biogenesis and partially counteracted the cardioprotective effect of omentin in vitro. Therefore, this study indicated that Rd promoted omentin secretion from adipocytes through the TBK1-AMPK pathway to improve mitochondrial biogenesis function via WNT5A/Ca2+ signaling pathway to ameliorate myocardial ischemia injury, which provided a new therapeutic mechanism and potential drugs for the treatment of HF.

AimsRight atrial (RA) dilatation may be important for patients' outcome in pulmonary arterial hypertension (PAH). The aim of this study was to examine the longitudinal RA and right ventricular (RV) remodelling in PAH patients using real-time three-dimensional echocardiography (3DE) and their relation to clinical outcome.

Background Data on pharmacological management during pregnancy are scarce. The aim of this study was to describe the type and frequency of cardiac medication used in pregnancy in patients with cardiovascular disease and to assess the relationship between medication use and fetal outcome. Methods and results Between 2007 and 2011 sixty hospitals in 28 countries enrolled 1321 pregnant women. All patients had structural heart disease (congenital 66%, valvular 25% or cardiomyopathy 7% or ischemic 2%). Medication was used by 424 patients (32%) at some time during pregnancy: 22% used beta-blockers, 8% antiplatelet agents, 7% diuretics, 2.8% ACE inhibitors and 0.5% statins. Compared to those who did not take medication, patients taking medication were older, more likely to be parous, have valvular heart disease and were less often in sinus rhythm. The odds ratio of fetal adverse events in users versus non-users of medication was 2.6 (95% CI 2.0–3.4) and after adjustment for cardiac and obstetric parameter was 2.0 (95% CI 1.4–2.7). Babies of patients treated with beta-blockers had a significantly lower adjusted birth weight (3140 versus 3240 g, p = 0.002). The highest rate of fetal malformation was found in patients taking ACE inhibitors (8%). Conclusion One third of pregnant women with heart disease used cardiac medication during their pregnancy, which was associated with an increased rate of adverse fetal events. Birth weight was significantly lower in children of patients taking beta-blockers. A randomized trial is needed to distinguish the effects of the medication from the effects of the underlying maternal cardiac condition.

AimsThree-dimensional (3D) speckle tracking echocardiography (3DSTE) has been shown to be an accurate and reliable clinical tool for the evaluation of global and regional left ventricular (LV) function through strain analysis, but the absence of normal values has precluded its widespread use in clinical practice. The aim of this prospective multicentre study was to establish normal reference values of LV strain parameters using 3DSTE in a large healthy population.

2016 ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HEART FAILURE. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

Myriad advances in all fields of cardiac imaging have stimulated and reflected new understanding of cardiac performance, myocardial damage and the mechanisms of heart failure. In this paper, the Heart Failure Association assesses the potential usefulness of innovative imaging modalities in enabling more precise diagnostic and prognostic evaluation, as well as in guiding treatment strategies. Many new methods have gradually penetrated clinical practice and are on their way to becoming a part of routine evaluation. This paper focuses on myocardial deformation and three-dimensional ultrasound imaging; stress tests for the evaluation of contractile and filling function; the progress of magnetic resonance techniques; molecular imaging and other sound innovations. The Heart Failure Association aims to highlight the ways in which paradigms have shifted in several areas of cardiac assessment. These include reassessing of the simplified concept of ejection fraction and implementation of the new parameters of cardiac performance applicable to all heart failure phenotypes; switching from two-dimensional to more accurate and reproducible three-dimensional ultrasound volumetric evaluation; greater tissue characterization via recently developed magnetic resonance modalities; moving from assessing cardiac function and congestion at rest to assessing it during stress; from invasive to novel non-invasive hybrid techniques depicting coronary anatomy and myocardial perfusion; as well as from morphometry to the imaging of pathophysiologic processes such as inflammation and apoptosis. This position paper examines the specific benefits of imaging innovations for practitioners dealing with heart failure aetiology, risk stratification and monitoring, and, in addition, for scientists involved in the development of future research.

Background & aims It is unclear whether the Mediterranean diet (MedDiet) has a favorable effect on blood pressure (BP) levels because among randomized controlled trials (RCTs) investigating the MedDiet-mediated BP reduction significant methodological and clinical differences are observed. The purpose of this study was to comprehensively assess the MedDiet BP-effect compared to the usual diet or another dietary intervention (e.g. low-fat diet) in adults with and without hypertension, accounting for methodological and clinical confounders. Methods We systematically searched Medline and the Cochrane Collaboration Library databases and identified 35 RCTs (13,943 participants). Random-effects model was used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted. Results Compared to the usual diet and all other active intervention diets the MedDiet reduced SBP and DBP (difference in means: −1.5 mm Hg; 95% CI: −2.8, −0.1; P = 0.035, and −0.9 mm Hg; 95% CI: −1.5, −0.3; P = 0.002, respectively). Compared only to the usual diet the MedDiet reduced SBP and DBP, while compared to all other active intervention diets or only to the low-fat diet the MedDiet did not reduce SBP and DBP. The MedDiet reduced DBP levels to a higher extent in trials with mean baseline SBP ≥130 mm Hg, while both SBP and DBP were reduced more in trials with a mean follow-up period ≥16 weeks. The quality of evidence was rated as moderate for both outcomes according to the grading of recommendations, assessment, development and evaluation (GRADE) approach. Conclusions The adoption of the MedDiet was accompanied by a relatively small, but yet significant BP reduction, while higher baseline SBP levels and longer follow-up duration enhanced the BP-lowering effect of the intervention. This meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020167308. Registry number CRD42020167308.

We have developed a new measure of myocardial viability, the water-perfusable tissue index (PTI), which is calculated from transmission, C15O, and H2(15)O positron emission tomography (PET) data sets. It is defined as the proportion of the total anatomical tissue within a given region of interest (ROI) that is capable of rapidly exchanging water and has units g (perfusable tissue)/g (total anatomical tissue). The aim of this study was to assess the prognostic value of PTI in predicting improvement in regional wall motion after successful thrombolysis for acute myocardial infarction (AMI) and to measure the myocardial blood flow to the perfusable tissue (MBFp, ml/min/g [perfusable tissue]). Furthermore, PTI was compared with 18FDG metabolic imaging in patients with old myocardial infarction (OMI).PET scans were performed in healthy volunteers (group 1, n = 8), patients with OMI (group 2, n = 15), and in patients who were successfully thrombolysed after an AMI (group 3, n = 11). Systolic wall thickening was measured by two-dimensional echocardiography within 2-4 days of AMI and after 4 months to assess contractile recovery. In the healthy volunteers, MBFp was 0.95 +/- 0.13 ml/min/g (perfusable tissue). PTI in these regions was 1.08 +/- 0.07 g (perfusable tissue)/g (total anatomical tissue), which was consistent with all normal myocardium being perfusable by water. In the OMI group, the ratio of the relative 18FDG activity to the relative MBFp defect (metabolism-flow ratio) was calculated for each asynergic segment. Regions in which the metabolism-flow ratio was greater than or equal to 1.20 were considered reversibly injured, whereas those in which the ratio was less than 1.20 were deemed irreversibly injured. PTI in the former group of regions (n = 9) was 0.75 +/- 0.14 g (perfusable tissue)/g (total anatomical tissue) and was significantly higher than in irreversibly injured regions (n = 6) (0.53 +/- 0.12 g [perfusable tissue]/g [total anatomical tissue], p less than 0.01). Values of MBFp were similar in these segments. Seven of 12 segments in the AMI patients showed improved systolic wall thickening on follow-up. PTI in these recovery segments was 0.88 +/- 0.10 g (perfusable tissue)/g (total anatomical tissue) (p = NS versus control). PTI in the nonrecovery regions was 0.53 +/- 0.11 g (perfusable tissue)/g (total anatomical tissue), which was similar to the segments in group 2 in which 18FDG uptake was absent. MBFp was similar in both the recovery and nonrecovery segments in the subacute phase.These data indicate that PTI may be a good prognostic indicator for the recovery of contractile function after successful thrombolysis and show that myocardial viability may be assessed by PET without metabolic imaging.

One hundred five unselected and consecutive patients were prospectively studied after acute transmural myocardial infarction to assess the incidence of mural thrombus formation and to relate the presence of thrombus to patient outcome in terms of systemic embolic events, functional class and survival. In 87 patients, optimal quality two-dimensional echocardiographic studies were obtained and were repeated at daily intervals to detect mural thrombus formation. The site of infarction was anterior in 53 patients and inferior in 34. On admission, all patients received subcutaneous heparin and antiplatelet agents (aspirin, dipyridamole); none received full anticoagulant therapy. Left ventricular mural thrombus was visualized between 2 and 11 days (median 6) after the clinical onset of infarction in 21 (40%) of the 53 patients with anterior infarction. No patients with inferior infarction had echo-cardiographic evidence of thrombus formation. During follow-up of 22 to 51 months (mean 39), none of the 21 patients with mural thrombus had clinical evidence of systemic embolism. One patient with inferior and one with anterior infarction had a cerebral embolus 7 days and 9 months, respectively, after the acute event, but neither of these patients had echocardiographic evidence of left ventricular thrombus at any stage. Echocardiography performed at 1 and 2 years of follow-up showed persistent evidence of thrombus in only 8 (31%) and 5 (24%) of the 21 patients, respectively. On admission, the functional class of patients with anterior myocardial infarction and thrombus was similar to that of patients without ventricular thrombus. Early in-hospital mortality was higher in those without thrombus (9 [28%] of 32 versus 2 [9%] of 21) (p < 0.001) and occurred earlier in time (mean 24 h versus 8 days) (p < 0.001). At 1 year of follow-up, patients with anterior infarction and thrombus formation had improvement in functional class compared with those who did not (p < 0.001). It is concluded that left ventricular mural thrombus is a common finding in patients sustaining anterior myocardial infarction. The incidence of systemic embolism, however, is low and does not justify full anticoagulation. Furthermore, as early mortality and morbidity were lower in patients wioh than in those without mural thrombus, mural thrombus, by offering mechanical support to infarcted myocardium, may protect against left ventricular rupture and improve functional class in the long term.

Previous assessments of myocardial viability using positron emission tomography (PET) relied on demonstration of glucose metabolism in hypoperfused asynergic segments using the glucose analogue [18F]2-fluoro-2-deoxyglucose (FDG). Recently, it was shown that myocardial viability could be assessed by calculating the water-perfusable tissue index (PTI) for the asynergic region. PTI represents the proportion of the myocardium that is capable of rapid transsarcolemmal exchange of water and thus perfusable by water. The aim of the present study was to assess myocardial viability by PET using PTI in patients undergoing coronary revascularization.Twelve patients with chronic coronary artery disease and previous myocardial infarction were studied. Analysis of transmission (tissue density) and 15O-labeled carbon monoxide (blood pool), and 15O-labeled water (myocardial blood flow [MBF]) emission PET data enabled the simultaneous quantification of MBF (ml.min-1.g perfusable tissue-1) and PTI (gram of perfusable tissue per gram of total anatomic tissue). In addition, PET imaging with FDG after 75-g oral glucose load was performed in eight patients. Preoperative echocardiography identified 33 hypocontractile and 26 control segments. Follow-up echocardiography performed 3 to 5 months later demonstrated 26 of 33 segments with improved wall motion (recovery) and seven of 33 segments without improvement (nonrecovery). MBF in the control segments (0.97 +/- 0.22 ml.min-1.g perfusable tissue-1) was significantly higher (p < 0.001) than in both the recovery (0.73 +/- 0.18 ml.min-1.g perfusable tissue-1) and the nonrecovery (0.45 +/- 0.11 ml.min-1.g perfusable tissue-1) segments. PTI in the recovery regions (0.99 +/- 0.15) was > or = 0.7 in all cases and slightly less than in control regions (1.10 +/- 0.15, p < 0.02). FDG uptake in these regions was 92 +/- 17% (n = 13) of the uptake in control segments with normal wall motion. In the nonrecovery group, PTI was 0.62 +/- 0.06 (p < 0.02 versus control and recovery) and always < 0.7. In the one patient in whom a comparison with metabolic imaging was made, FDG uptake was 46% of the uptake in a reference region with normal wall motion.These data showed that contractile recovery occurred only in segments where PTI was > or = 0.7, suggesting that > or = 70% of myocardial tissue in a given asynergic segment should be perfusable by water to enable contractile recovery. There was good agreement between the PTI and FDG methods for predicting improvements in regional wall motion after revascularization. Although further studies should be performed in a larger patient group, the preliminary results are promising and suggest that PTI may be a good predictor of contractile recovery after coronary revascularization.

Nineteen patients with syndrome X (typical exertional angina, positive exercise test response [at least 0.1 mV of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries) underwent continuous 48-hour electrocardiographic (ECG) monitoring during unrestricted daily life. Fifty-eight ischemic episodes of at least 0.1 mV of ST-segment depression were observed in the same ECG leads that showed ST depression during stress testing: 28 (48%) were accompanied by anginal pain and 30 (52%) were asymptomatic. No significant differences were found between painful and silent ST-segment depression with regard to the number of episodes, their temporal distribution, magnitude, duration or heart rate (HR) at onset of ST-segment depression. In the minute preceding ischemic ST shifts, HR did not change in 33% of episodes or increased by less than 10 beats/min in 28%. HR at onset of ST depression was significantly lower during ambulatory ECG monitoring than during exercise testing (98 +/- 18 vs 117 +/- 18 beats/min, p less than 0.01). During ambulatory monitoring, 85 episodes of sinus tachycardia (exceeding by 10 to 80 beats/min the HR that triggered ischemia during exercise testing) occurred in the absence of angina or ST-segment shifts. The results of this study suggest that in patients with syndrome X, myocardial ischemia frequently develops during daily life; silent ischemia is an important component of this syndrome; and increased oxygen demand in the presence of impaired coronary vasodilatory capacity is not the only cause of myocardial ischemia. Active mechanisms that transiently reduce coronary flow may act and explain occurrence of angina at rest and with minimal exertion.

We sought to assess the feasibility and accuracy of myocardial contrast echocardiography (MCE) using standard imaging approaches for the detection of perfusion defects in patients who had a myocardial infarction (MI).Myocardial contrast echocardiography may be more versatile than perfusion scintigraphy for identifying the presence and extent of perfusion defects after MI. However, its reliability in routine practice is unclear.Fundamental or harmonic MCE was performed with continuous or triggered imaging in 203 patients with a previous MI using bolus doses of a perfluorocarbon-filled contrast agent (NC100100). All patients underwent single-photon emission computed tomography (SPECT) after the injection of technetium-99m (Tc-99m) sestamibi at rest. Quantitative and semiquantitative SPECT, wall motion and digitized echocardiographic data were interpreted independently. The accuracy of MCE was assessed for detection of segments and patients with moderate and severe sestamibi-SPECT defects, as well as for detection of patients with extensive perfusion defects (>12% of left ventricle).In segments with diagnostic MCE, the segmental sensitivity ranged from 14% to 65%, and the specificity varied from 78% to 95%, depending on the dose of contrast agent. Using both segment- and patient-based analysis, the greatest accuracy and proportion of interpretable images were obtained using harmonic imaging in the triggered mode. For the detection of extensive defects, the sensitivity varied from 13% to 48%, with specificity from 63% to 100%. Harmonic imaging remained the most accurate approach. Time since MI and SPECT defect location and intensity were all determinants of the MCE response. The extent of defects on MCE was less than the extent of either abnormal wall motion or SPECT abnormalities. The combination of wall motion and MCE assessment gave the best balance of sensitivity (46% to 55%) and specificity (82% to 83%).Although MCE is specific, it has limited sensitivity for detection of moderate or severe perfusion defects, and it underestimates the extent of SPECT defects. The best results are obtained by integration with wall motion. More sophisticated methods of acquisition and interpretation are needed to enhance the feasibility of this technique in routine practice.

Transesophageal echocardiographfc studies were prospectively performed in 152 consecutive patients older than age 40 years referred to the echocardiography laboratory to assess the prevalence of atherosclerosis in the thoracic aorta and relate this to a history of systemic embolization. Forty-four patients (29%) had at least 1 atherosclerotic lesion in the thoracic aorta. This was associated with a higher prevalence of coronary artery disease (78% of all patients with coronary artery disease), carotid artery disease (88% of all patients with carotid artery disease) and peripheral vascular disease (all symptomatic patients). Forty-two of all patients (28%) had systemic emboli, 20 (48%) of whom had at least 1 atheromatous lesion in the thoracic aorta. Conversely, only 24 of 110 patients (22%) without previous systemic emboli had atheromatous lesions (p < 0.001). It is concluded that atherosclerotic lesions in the thoracic aorta can readily be identified with transesophageal echocardiography. The detection of atherosclerotic plaques of the aorta represents a marker of diffuse atherosclerotic disease, often associated with carotid, coronary and peripheral vascular disease and with the occurrence of systemic emboli. Transesophageal echocardiography may be used serially to investigate whether dietary or pharmacologic maneuvers, or both, can shrink established atherosclerotic plaques in the thoracic aorta.

Doppler echocardiography was used to assess diastolic function in 40 patients with hypertrophic cardiomyopathy and to relate it to the patients' symptoms, anaerobic threshold and maximal oxygen consumption during cardiopulmonary exercise testing. The patients had a smaller early (E wave) (p < 0.01), higher late (A wave) (p < 0.05) mitral diastolic flow velocity, larger A/E ratio (p < 0.01), longer isovolumetric relaxation time and E wave duration (p < 0.001) and slower deceleration rate of the E wave (p < 0.001) than 40 age- and gender-matched normal subjects. In the patients with hypertrophic cardiomyopathy, maximal oxygen consumption and anaerobic threshold were, respectively, 26.3 ± 9.2 and 21.1 ± 6.1 ml/kg per min compared with 47 (range 39 to 68) (p < 0.01) and 41 (range 27 to 58) ml/kg per min (p < 0.01) in normal subjects. There was no relation between Doppler indexes and symptoms but symptomatic patients had lower maximal oxygen consumption and anaerobic threshold compared with asymptomatic patients (21.4 ± 7 vs. 30.7 ± 10, p < 0.001 and 18.6 ± 4.7 vs. 23.1 ± 5.7, respectively, p < 0.001). In conclusion, Doppler echocardiography can identify abnormalities of left ventricular filling in patients with hypertrophic cardiomyopathy. However, these indexes measured at rest do not correspond to the patient's professed symptomatic status or exercise capacity measured objectively. Conversely, cardiopulmonary exercise testing reveals a depressed maximal oxygen consumption and anaerobic threshold even in the least symptomatic patients.

The purpose of this research was to evaluate right ventricular (RV) remodeling after six months of cardiac resynchronization therapy (CRT).Cardiac resynchronization therapy is beneficial in patients with end-stage heart failure. The effect of CRT on RV size is currently unknown. Accordingly, the effects of CRT on RV size, severity of tricuspid regurgitation, and pulmonary artery pressure were evaluated.Fifty-six consecutive patients with end-stage heart failure (52% ischemic cardiomyopathy), left ventricular (LV) ejection fraction (EF) < or =35%, QRS duration >120 ms, and left bundle branch block were included. Clinical parameters, LV volumes, LVEF, LV dyssynchrony, and RV chamber size were assessed at baseline and after six months of CRT; LV dyssynchrony was assessed using tissue Doppler imaging.Clinical parameters improved significantly; LV dyssynchrony was acutely reduced after CRT and remained unchanged at six-month follow-up. Left ventricular EF improved significantly from 19 +/- 6% to 26 +/- 8% (p < 0.001), and LV end-diastolic volume decreased from 257 +/- 98 ml to 227 +/- 86 ml (p < 0.001). Right ventricular annulus decreased significantly from 37 +/- 9 mm to 32 +/- 10 mm, RV short-axis from 29 +/- 11 mm to 26 +/- 7 mm, and RV long-axis from 89 +/- 11 mm to 82 +/- 10 mm (all p < 0.001). Left ventricular and RV reverse remodeling were only observed in patients with substantial LV dyssynchrony at baseline. Finally, significant reductions in severity of tricuspid regurgitation and pulmonary artery pressure were observed.Cardiac resynchronization therapy results in significant reverse LV and RV remodeling after six months of CRT in patients with LV dyssynchrony. Moreover, CRT leads to a reduction of the severity of tricuspid regurgitation and a decrease in pulmonary artery pressure.

Right ventricular (RV) mass and volume calculations are important correlates of survival in patients with pulmonary arterial hypertension (PAH). We tested the hypothesis that RV mass, volumes and function could be measured accurately with real-time three-dimensional echocardiography (3DE) in patients with PAH and compared those against cardiac magnetic resonance (CMR).Sixty consecutive PAH patients and 20 normals were examined with 3DE and CMR. RV end-diastolic volumes (EDV), end-systolic (ESV), stroke volume (SV), ejection fraction (EF), and mass were measured in all patients and in normals. Two independent observers assessed variability using the Bland-Altman analysis agreement. RV volumes (in mL) and mass were similar between 3DE and CMR in PAH patients: [EDV (in mL) 183.2 +/- 38 vs. 187.3 +/- 41, P = 0.32; ESV (in mL) 122 +/- 33 vs. 126 +/- 36, P = 0.99; SV (in mL) 63 +/- 15 vs. 65 +/- 19, P = 0.06; EF (in %) 33 +/- 7 vs. 31 +/- 9, P = 0.16 and RV mass (g) 99 +/- 20 vs. 96 +/- 22, P = 0.42], respectively. Interobserver variability was similar between 3DE and CMR in PAH for all variables, with CMR showing less interobserver variability for EDV compared with 3DE in both patients and normals (patients: mean bias: CMR-EDV: 0.4 +/- 16 mL vs. 3DE-EDV: 6.9 +/- 17.9 and in normals: CMR-EDV: 0.1 +/- 9.8 vs. 3DE-EDV: 5.7 +/- 16.3, respectively), whereas EF and RV mass were poorly reproducible with no correlation between observers for 3DE and CMR.RV remodelling in PAH patients can be accurately assessed with both 3DE and CMR. Both modalities are robust and reproducible with CMR being more reproducible for measurements of EF and RV mass.

Abstract To examine whether QTc and QTc dispersion across the leads of a surface electrocardiogram (ECG) are different in patients with hypertrophic cardiomyopathy (HCM) compared with normal subjects, we measured QT and calculated QTc in all 12 leads of a surface ECG in 24 patients with HCM and in 20 age‐ and sex‐matched normal control subjects. Maximal QTc was prolonged in HCM patients (465±24 ms) compared with controls (410±20 ms) (p&lt;0.001). QTc dispersion defined as the difference of maximum‐minimum QTc was also greater in HCM patients (71±21 ms) compared with normals (35±11 ms) (p&lt;0.001). A correlation was found between the degree of left ventricular hypertrophy expressed by the maximal wall thickness and maximal QTc (r=0.48, p&lt;0.02). However, QTc dispersion did not correlate with maximal wall thickness. Thus, patients with HCM show a prolonged QTc (&gt;440 ms) and increased QTc dispersion compared with normal subjects. In addition, the degree of left ventricular hypertrophy correlates with maximal QTc. The presence of a prolonged QT with increased regional dispersion may be associated with the occurrence of serious ventricular arrhythmia and sudden death in HCM.

Hypertrophic Cardiomyopathy is characterized by unexplained left ventricular hypertrophy. It is uncertain, however, to what extent the right ventricle is also thickened. Right ventricular hypertrophy is found at autopsy in patients who die suddenly but, until recently, systematic evaluation of right ventricular morphology has not been feasible. In this two-dimensional echocardiographic study, a total of 4 to 10 (median 7) right ventricular wall thickness measurements were made from six right ventricular views in 73 patients with hypertrophic cardiomyopathy. Fortyone normal subjects were also studied for comparison. Thirty-two (44%) of the 73 patients had right ventricular hypertrophy with at least two of the wall thickness measurements exceeding 2 standard deviations (SD) from the mean value in the normal subjects. Right ventricular hypertrophy was mild (≤ mm) in 24 patients, moderate (9 to 12 mm) in 7 and severe (>12 mm) in 1. The coefficient of variation of right ventricular wall thickness measurements was similar in normal subjects and patients with and without right ventricular hypertrophy (17 ± 7, 11± 8 and 10 ± 8, respectively). The hypertrophy was concentric, with a current of variation of 25% in all but one patient. There was a strong correlation of maximal right and mean left ventricular wall thickness (r = 0.643, p < 0.001). Right ventricular hypertrophy was not associated with the occurrence of secondary pulmonary hypertension, but was more common in patients with dyspnea on exertion (p < 0.05), severe left ventricular hypertrophy (p < 0.007), supraventricular arrhythmias (p < 0.005) and ventricular tachycardia (p = 0.02) during electrocardiographic monitoring. Stepwise logistic regression analysis revealed that mean left ventricular wall thickness and supraventricular arrhythmias were independent risk factors for right ventricular hypertrophy. Thus, the presence of right ventricular hypertrophy was associated with more severe disease.

Left ventricular non-compaction (LVNC) is a rare disorder that results in multiple deep trabeculations within the left ventricular myocardium. It is thought to be due in part, to an arrest of myocardial development but more recent evidence suggests that some cases may actually be acquired while other isolated cases have regressed with time. Transthoracic echocardiography remains the imaging modality of choice for LVNC where diagnosis is based on the identification of multiple prominent ventricular trabeculations with intertrabecular spaces communicating with the ventricular cavity. There is a broad and potentially confusing spectrum of clinical symptomatology in patients with ventricular non-compaction meaning that the primary diagnosis is often missed. Complications such as potentially malignant arrhythmias, left ventricular failure, and cardioembolic events arising as a result of non-compaction must be treated in an attempt to decrease morbidity and mortality from this disorder. The ultimate outcome for patients remains unclear with some boasting a prolonged asymptomatic course, to others displaying a rapid deterioration of left ventricular systolic function, leading to heart transplantation or death. In conclusion, LVNC while remaining a rare cardiomyopathy, shall probably be diagnosed with increasing frequency in the coming years because of heightened awareness about its natural history and clinical manifestations and because of the improved modalities available for cardiac imaging.

Atrial tachyarrhythmias are a common complication of atrial septal defects. The objective was to determine the effect of atrial septal defect closure on pre-existing atrial tachyarrhythmias and to investigate if such an effect is present after either surgical or percutaneous closure. Medline, EMBASE, Cochrane Library, and Google Scholar databases were searched between 1967 and 2009. The search was expanded using the 'related articles' function and reference lists of key studies. All studies reporting pre- and post- closure incidence (or prevalence) of atrial tachyarrhythmias in the same patient groups were included. Data were independently extracted by two authors according to a pre-defined protocol. Incongruities were settled by consensus decision. Twenty six studies were identified including 1841 patients who underwent surgical closure and 945 who underwent percutaneous closure. Meta-analysis using a random effects model demonstrated a reduction in the prevalence of atrial tachyarrhythmias following atrial septal defect closure [OR = 0.66 (95% CI 0.57-0.77)]. This effect was demonstrated after both percutaneous [OR = 0.49 (95% CI 0.32-0.76)] and surgical closure [OR = 0.72 (95% CI 0.60-0.87)]. Immediate (<30 days) and mid-term (30 days - 5 years) follow-up also demonstrated a reduction in AT prevalence [ORs of 0.80 (95% CI 0.66-0.97) and 0.47 (95% CI 0.36-0.62) respectively]. Atrial septal defect closure, whether surgical or percutaneous, is associated with a reduction in the post-closure prevalence of pre-existing atrial tachyarrhythmias and atrial fibrillation in the short to medium term.

Vascular stiffening in distal pulmonary arteries plays a key role in the early pathogenesis and progression of pulmonary arterial hypertension (PAH). Pathophysiologic cellular responses to vascular stiffness include upregulation of signaling pathways that promote further vascular remodeling, a process known as mechanobiological feedback. Inflammatory signaling and metabolic shifts, particularly upregulation of aerobic glycolysis and glutaminolysis, have also recently been shown to occur downstream of pulmonary vascular stiffening, and are known to play a critical role in PAH development. In this chapter, we will focus on the specific mechanisms underlying these cellular responses. Vascular cell mechanosensing involves the integration of signals from the cell surface, relayed by molecules such as integrins, small GTPases, membrane-associated kinases, and the actin cytoskeleton, into a downstream transcriptional program via nuclear-cytosolic shuttling proteins. Targeting these mechanosensing pathways offers the potential to disrupt mechanobiological feedback and prevent or reverse pathologic pulmonary vascular remodeling in PAH.

The European Association for Cardiovascular Imaging (EACVI) has outlined the rationale for setting appropriate use criteria (AUC) in cardiovascular (CV) imaging. Transthoracic echocardiography (TTE) is the most common imaging modality in CV disease and is a central tool in diagnosis, follow-up, management planning and intervention. The purpose of AUC is to inform referrers, both to avoid under-use, which may result in incomplete or incorrect diagnosis and treatment, and also over-use, which may delay correct diagnosis, lead to 'treatment cascade', and wastes resources. The first step in defining AUC for TTE in the adult has been for a panel of experts in echocardiography to review the evidence, guidelines, recommendations, and position papers from the European Society of Cardiology, EACVI and other specialist societies, and current state-of-the-art clinical practice. The attached document summarizes this work, which will be used to under-pin the development of AUC.

Background Trastuzumab improves dramatically the prognosis of HER2‐positive breast cancer patients, but it may lead to cardiotoxicity with left ventricular (LV) systolic dysfunction. Its effects on right ventricular (RV) function have not however been elucidated. We sought to assess LV and RV deformation mechanics during treatment with trastuzumab in breast cancer patients. Methods and results We studied 101 consecutive women (mean age 54.3 ± 11.4 years) receiving trastuzumab for 12 months; 62 of them (61.4%) had previously received anthracyclines and 26 (25.7%) were receiving taxanes concurrently with trastuzumab. Comprehensive two‐dimensional echocardiography with speckle tracking imaging of LV and RV global longitudinal strain (GLS) and RV free wall longitudinal strain (FWLS) analyses were performed at baseline and every 3 months up to treatment completion. Cardiotoxicity was defined as a decrease of baseline LV ejection fraction &gt; 10 percentage units to a value &lt; 50%. At 3 months, only LV GLS was significantly reduced (−19.5 ± 2.7 to −18.7 ± 2.8, P = 0.0410), while at 6 months, LV GLS, RV GLS and RV FWLS had significantly declined reaching their lowest values (−17.9 ± 6.1, P = 0.002, −19.6 ± 5.2, P = 0.003 and −19.7 ± 5.6, P = 0.004, respectively). Ten women (9.9%) developed cardiotoxicity. A RV GLS percent change of −14.8% predicted cardiotoxicity with 66.7% sensitivity and 70.8% specificity (area under the curve 0.68, 95% confidence interval 0.54–0.81), classifying correctly 90% of women with cardiotoxicity. This cut‐off is quite similar to the 15% change of LV GLS previously suggested as predictive of cardiotoxicity. Conclusions Deformation mechanics of both the left and right ventricle follow similar temporal pattern and degree of impairment during trastuzumab therapy, confirming the global and uniform effect of trastuzumab on myocardial function.

Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired regarding its pathogenesis and pathophysiology does not allow us to treat it efficiently. It is not possible to arrest its progressive nature, and the available therapies are limited to symptomatic treatment. Furthermore, both the diagnosis and prognosis are frequently uncertain, whilst the ability to predict its occurrence is very limited. MicroRNAs are small non-coding RNAs discovered two decades ago, and present great interest given their ability to regulate almost every aspect of the cell function. A lot of evidence regarding the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years. Differentially expressed miRNAs are characteristic of both mild and severe PE. In many cases they target signaling pathway-related genes that result in altered processes which are directly involved in PE. Immune system, angiogenesis and trophoblast proliferation and invasion, all fundamental aspects of placentation, are controlled in various degrees by miRNAs which are up- or downregulated. Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.

Despite the high prevalence of hypertension (HTN), only a small proportion of the hypertensive patients will ultimately develop hypertensive crisis. In fact, some patients with hypertensive crisis do not report a history of HTN or previous use of antihypertensive medication. The majority of the patients with hypertensive crisis often report non-specific symptoms, whereas heart-related symptoms (dyspnea, chest pain, arrhythmias, and syncope) are less common. Hypertensive crises can be divided into hypertensive emergencies or hypertensive urgencies according to the presence or absence of acute target organ damage, respectively. This differentiation is an extremely useful classification in clinical practice since a different management is needed, which in turn has a significant effect on the morbidity and mortality of these patients. Therefore, it is very crucial for the physician in the emergency department to identify the hypertensive emergencies and to manage them through blood pressure lowering medications in order to avoid further target organ damage or deterioration. The aim of this narrative review is to summarize the recent evidence in an effort to improve the awareness, recognition, risk stratification, and treatment of hypertensive crisis in patients referred to the emergency department.

Abstract Acute heart failure is one of the main diagnostic and therapeutic challenges in clinical practice due to a non‐specific clinical manifestation and the urgent need for timely and tailored management at the same time. In this position statement, the Heart Failure Association aims to systematize the use of various imaging methods in accordance with the timeline of acute heart failure care proposed in the recent guidelines of the European Society of Cardiology. During the first hours of admission the point‐of‐care focused cardiac and lung ultrasound examination is an invaluable tool for rapid differential diagnosis of acute dyspnoea, which is highly feasible and relatively easy to learn. Several portable and stationary imaging modalities are being increasingly used for the evaluation of cardiac structure and function, haemodynamic and volume status, precipitating myocardial ischaemia or valvular abnormalities, and systemic and pulmonary congestion. This paper emphasizes the central role of the full echocardiographic examination in the identification of heart failure aetiology, severity of cardiac dysfunction, indications for specific heart failure therapy, and risk stratification. Correct evaluation of cardiac filling pressures and accurate prognostication may help to prevent unscheduled short‐term readmission. Alternative advanced imaging modalities should be considered to assist patient management in the pre‐ and post‐discharge phase, including cardiac magnetic resonance, computed tomography, nuclear studies, and coronary angiography. The Heart Failure Association addresses this paper to the wide spectrum of acute care and heart failure specialists, highlighting the value of all available imaging techniques at specific stages and in common clinical scenarios of acute heart failure.

Objectives The clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK. Methods We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention. Results Mean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p&lt;0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for. Conclusion Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

Phenotypic heterogeneity in hypertrophic cardiomyopathy (HC) makes definitive diagnosis difficult, particularly during family screening. We studied the electrocardiogram (ECG) as a potential initial screening test in patients with HC. Using accepted diagnostic criteria, we examined the ECGs and echocardiograms of 159 patients with a confirmed clinical or genetic diagnosis of HC. An abnormal ECG was found in 154 patients (97%) while only 146 (92%) showed an abnormal echocardiogram. Of the former, 9 patients (6%) had normal echocardiograms and had been diagnosed on the basis of identification of a mutation in the beta myosin heavy chain gene (n = 8) or obligate carrier status (n = 1). Only 1 of these 9 patients was under age 20, the time at which hypertrophy is normally expressed on the echocardiogram. The remaining 5 patients (3%) without ECG abnormality consisted of 1 patient with an echocardiogram clearly diagnostic of HC and 4 clinically normal patients (aged 13, 24, 29, and 33 years) with normal echocardiograms who had been diagnosed by mutation identification (n = 3) or obligate carrier status (n = 1). Thus only these latter 4 patients (3%) would not have been diagnosed as having HC based on an abnormal ECG and/or abnormal echocardiogram. Screening relatives for HC by ECG criteria alone detects all those whom an echocardiogram will diagnose. While echocardiography aids in the specificity of HC diagnosis, the ECG, within the context of a family with a proven case of HC, is a more sensitive marker of the disease. It is therefore both a cost-effective and useful tool for screening those to proceed to echocardiography.

Coronary vasodilator reserve is reduced in hypertrophic cardiomyopathy and secondary left ventricular hypertrophy despite angiographically normal coronaries. The aim of the present study was to assess whether quantitative differences exist between these conditions.Using positron emission tomography with H2(15)O, myocardial blood flow was measured at baseline and following intravenous dipyridamole (0.56 mg.kg-1) in 12 hypertrophic cardiomyopathy patients (age 34 (11) years, mean (SD), all male), 16 secondary left ventricular hypertrophy patients (age 58 (20) years, P < 0.01 vs hypertrophic cardiomyopathy; 10 female) and 40 normal controls (age 54 (20), 13 female). In view of the known decline of post-dipyridamole myocardial blood flow with age, myocardial blood flow was compared between the patient groups and appropriately matched subsets of the total control group.Baseline myocardial blood flow in the hypertrophic cardiomyopathy patients was 0.82 (0.23) ml.min-1.g-1 vs 0.94 (0.14) ml.min-1.g-1 in its matched control group, P = ns. For the secondary left ventricular hypertrophy patient group, baseline myocardial blood flow was 1.17 (0.40) ml.min-1.g-1 vs 1.06 (0.28) ml.min-1.g-1 for the secondary left ventricular hypertrophy matched control group, P = ns. Following dipyridamole, myocardial blood flow was 1.64 (0.44) ml.min-1.g.-1 in hypertrophic cardiomyopathy patients vs 3.50 (0.95) ml.min-1.g-1 for the hypertrophic cardiomyopathy matched control group, P = 0.0001. For the left ventricular hypertrophy patients, post-dipyridamole myocardial blood flow was 2.27 (0.60) ml.min-1.g-1 vs 2.94 (1.29) ml.min-1.g-1 for the left ventricular hypertrophy controls, P = 0.06. Coronary vasodilator reserve (dipyridamole-myocardial blood flow/baseline-myocardial blood flow) was 2.05 (0.61) for hypertrophic cardiomyopathy patients vs 3.81 (0.98) for the hypertrophic cardiomyopathy controls (P = 0.0001, patients vs controls) and 2.06 (0.62) for left ventricular hypertrophy patients vs 2.90 (1.38) for the left ventricular hypertrophy controls, P < 0.03 patients vs controls. After correction of baseline myocardial blood flow for baseline heart rate x systolic pressure product, coronary vasodilator reserve for the hypertrophic cardiomyopathy patients was 2.06 (1.06) vs 4.34 (1.54) for the hypertrophic cardiomyopathy controls. P = 0.0002 and in the secondary left ventricular hypertrophy patients, the values were 2.13 (0.64) vs 2.89 (1.42) in the secondary left ventricular hypertrophy controls, P < 0.05.In both hypertrophic cardiomyopathy and secondary left ventricular hypertrophy, the computed coronary vasodilator reserve is impaired, even after correction for baseline cardiac work. However, the extent of the reduction is greater in the hypertrophic cardiomyopathy patients. In the blunting of vasodilator reserve of secondary left ventricular hypertrophy, the patients' greater hyperaemic response is partly offset by the higher baseline myocardial blood flow.

Background —Conventional and tissue Doppler echocardiographically derived myocardial velocity gradients (MVGs) were used to characterize the myocardium in patients with Friedreich’s ataxia (FRDA), and the relationship between MVGs and the mutation in the FRDA gene, a GAA triplet repeat expansion, was investigated. Methods and Results —We studied 29 patients with FRDA (10 men, mean age 31±9 years) who were homozygous for the GAA expansion in the FRDA gene and were without cardiac symptoms. A comparison was made with a group of 30 age-matched control subjects. In patients with FRDA, interventricular septal thickness (1.17±0.26 versus 0.85±0.13 cm, P &lt;0.005), posterior left ventricular wall thickness (1.00±0.24 versus 0.88±0.15 cm, P &lt;0.01), and left atrial diameter (3.3±0.5 versus 2.9±0.3 cm, P =0.01) were increased compared with control subjects. MVGs were reduced in FRDA during systole (3.1±1.2 versus 4.5±0.5 s −1 , P &lt;0.0001) and in early diastole (4.9±2.7 versus 8.8±1.8 s −1 , P &lt;0.0001) but increased in late diastole (2.0±1.3 versus 1.1±0.9 s −1 , P &lt;0.01). The strongest relationship was seen between age-corrected early diastolic MVGs and the GAA expansion in the smaller allele of the FRDA gene ( r =−0.68, P &lt;0.0001). Conclusions —MVGs offer a means of further characterizing the myocardial abnormalities in patients with FRDA. Early diastolic MVGs appear to relate most closely to the genetic abnormality and the consequential reduction in frataxin protein.

This study was conducted to determine the myocardial beta-adrenoceptor density as a marker of sympathetic function in patients with hypertrophic cardiomyopathy and normal control subjects.Although some cases of hypertrophic cardiomyopathy are familial with an autosomal dominant pattern of inheritance, there remains a substantial proportion of cases in which neither a family history nor genetic abnormalities can be demonstrated. Additional abnormalities, both genetic and acquired, may be important in the phenotypic expression of this condition. Clinical features of the disease and metabolic studies suggest an increased activity of the sympathetic nervous system.Eleven patients with hypertrophic cardiomyopathy, none of whom had previously received beta-blocking drugs, and eight normal control subjects underwent positron emission tomography to evaluate regional left ventricular beta-adrenoceptor density and myocardial blood flow using carbon-11-labeled CGP 12177 and oxygen-15-labeled water as tracers. Plasma catecholamines were also measured.Mean (+/- SD) myocardial beta-adrenoceptor density was significantly less in the hypertrophic cardiomyopathy group than in the control group (7.70 +/- 1.86 vs. 11.50 +/- 2.18 pmol/g tissue, p < 0.001). Myocardial blood flow was similar in both groups (0.91 +/- 0.22 vs. 0.91 +/- 0.21 ml/min per g, p = NS). The distribution of beta-adrenoceptor density was uniform throughout the left ventricle in both groups. In the hypertrophic cardiomyopathy group, there was no correlation between regional wall thickness and myocardial beta-adrenoceptor density. There were no significant differences in either plasma norepinephrine or epinephrine concentrations between the two groups.There is a diffuse reduction in myocardial beta-adrenoceptor density in patients with hypertrophic cardiomyopathy in the absence of significantly elevated circulating catecholamine concentrations. This most likely reflects downregulation of myocardial beta-adrenoceptors secondary to increased myocardial concentrations of norepinephrine and is consistent with the hypothesis that cardiac sympathetic drive is increased in this condition.

The differential diagnosis between restrictive cardiomyopathy (RCM) and constrictive pericarditis (CP) is challenging and, despite combined information from different diagnostic tests, surgical exploration is often necessary.A group of 55 subjects (mean age, 63+/-11 years; 36 men and 19 women) were enrolled in the study; 15 had RCM, 10 had CP, and 30 were age-matched, normal controls. The diagnosis of RCM was supported by a biopsy; in the CP group, the diagnosis was confirmed either surgically or at autopsy. All patients underwent a transthoracic echocardiogram that included the assessment of Doppler myocardial velocity gradient (MVG), as measured from the left ventricular posterior wall during the predetermined phases of the cardiac cycle. MVG was lower (P<0.01) in RCM patients compared with both CP patients and normal controls during ventricular ejection (2. 8+/-1.2 versus 4.4+/-1.0 and 4.7+/-0.8 s(-1), respectively) and rapid ventricular filling (1.9+/-0.8 versus 8.7+/-1.7 and 3.7+/-1.4 s(-1), respectively). Additionally, during isovolumic relaxation, MVG was positive in RCM patients and negative in both CP patients and normal controls (0.7+/-0.4 versus -1.0+/-0.6 and -0.4+/-0.3 s(-1), respectively; P<0.01). During atrial contraction, MVG was similarly low (P<0.01) in both RCM and CP patients compared with normal controls (1.6+/-1.7 and 1.7+/-1.8 versus 3.8+/-0.9 s(-1), respectively).Doppler myocardial imaging-derived MVG, as measured from the left ventricular posterior wall in early diastole during both isovolumic relaxation and rapid ventricular filling, allows for the discrimination of RCM from CP.

The diagnosis of cardiac sarcoidosis, particularly when there is no overt systemic involvement, is frequently delayed because of its varied manifestations.Focal left ventricular wall motion abnormalities were recognised in five patients with sarcoidosis.Three patients showed abnormal regional wall motion in the basal portion of the ventricular septum and free wall with sparing of the apex.The angiographic appearances supported the echocardiographic findings which were atypical of ischaemic heart disease.The remaining two patients both had diffuse left ventricular hypokinesia, with a focal abnormality that was most pronounced in the anteroapical region; this pattern is often seen with coronary disease.The recognition by echocardiography or angiography of focal abnormalities of wall motion affecting the basal portion of the ventricular septum should suggest the possibility of myocardial sarcoidosis even in the absence of recognised systemic manifestations.

Stress echocardiography today has matured into a robust and reliable technique not only for the diagnosis of suspected coronary artery disease (CAD) but also for the accurate risk stratification of patients with suspected and established CAD. This is mainly because of rapid advances in image acquisition, digital display, and the development of harmonic and contrast imaging. Stress echocardiography today is also utilised in patients with heart failure both for assessing the cause of heart failure and determining the extent of hibernating myocardium. With advances in myocardial perfusion imaging, stress echocardiography now allows simultaneous assessment of myocardial function and perfusion. Tissue Doppler imaging allows quantitation of wall motion. Ready availability and reliability makes stress echocardiography a cost effective technique for the assessment of CAD.

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease.

Restrictive cardiomyopathies constitute a heterogenous group of heart muscle conditions that all have, in common, the symptoms of heart failure. Diastolic dysfunction with preserved systolic function is often the only echocardiographic abnormality that may be noted, although systolic dysfunction may also be an integral part of some specific pathologies, particularly in the most advanced cases such as amyloid infiltration of the heart. By far, the majority of restrictive cardiomyopathies are secondary to a systemic disorder such as amyloidosis, sarcoidosis, scleroderma, haemochromatosis, eosinophilic heart disease, or as a result of radiation treatment. The much more rare diagnosis of idiopathic restrictive cardiomyopathy is supported only by the absence of specific pathology on either endomyocardial biopsies or at post-mortem. Restrictive cardiomyopathy is diagnosed based on medical history, physical examination, and tests: such as blood tests, electrocardiogram, chest X-ray, echocardiography, and magnetic resonance imaging. With its wide availability, echocardiography is probably the most important investigation to identify the left ventricular dysfunction and should be performed early and by groups that are familiar with the wide variety of aetiologies. Finally, on rare occasions, the differential diagnosis from constrictive pericarditis may be necessary.

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 …

Contrast-enhanced ultrasound imaging is a radiation-free diagnostic tool that uses biocompatible ultrasound contrast agents (UCAs) to improve image clarity. UCAs, which do not contain dye, often salvage “technically difficult” ultrasound scans, increasing the accuracy and reliability of a front-line ultrasound diagnosis, reducing unnecessary downstream testing, lowering overall health care costs, changing therapy, and improving patient care. Two UCAs currently are approved and regulated by the US Food and Drug Administration. They have favorable safety profiles and risk/benefit ratios in adult and pediatric populations, including compromised patients with severe cardiovascular diseases. Nevertheless, these UCAs are contraindicated in patients with known or suspected right-to-left, bidirectional, or transient right-to-left cardiac shunts. These patients, who constitute 10% to 35% of the general population, typically receive no UCAs when they undergo echocardiography. If their echocardiographic images are suboptimal, they may receive inappropriate diagnosis and treatment, or they may be referred for additional diagnostic testing, including radiation-based procedures that increase their lifetime risk for cancer or procedures that use contrast agents containing dye, which may increase the risk for kidney damage. An exhaustive review of current peer-reviewed research demonstrated no scientific basis for the UCA contraindication in patients with known or suspected cardiac shunts. Initial safety concerns were based on limited rodent data and speculation related to macroaggregated albumin microspheres, a radioactive nuclear imaging agent with different physical and chemical properties and no relation to UCAs. Radioactive macroaggregated albumin is not contraindicated in adult or pediatric patients with cardiac shunts and is routinely used in these populations. In conclusion, the International Contrast Ultrasound Society Board recommends removal of the contraindication to further the public interest in safe, reliable, radiation-free diagnostic imaging options for patients with known or suspected cardiac shunts and to reduce their need for unnecessary downstream testing. Contrast-enhanced ultrasound imaging is a radiation-free diagnostic tool that uses biocompatible ultrasound contrast agents (UCAs) to improve image clarity. UCAs, which do not contain dye, often salvage “technically difficult” ultrasound scans, increasing the accuracy and reliability of a front-line ultrasound diagnosis, reducing unnecessary downstream testing, lowering overall health care costs, changing therapy, and improving patient care. Two UCAs currently are approved and regulated by the US Food and Drug Administration. They have favorable safety profiles and risk/benefit ratios in adult and pediatric populations, including compromised patients with severe cardiovascular diseases. Nevertheless, these UCAs are contraindicated in patients with known or suspected right-to-left, bidirectional, or transient right-to-left cardiac shunts. These patients, who constitute 10% to 35% of the general population, typically receive no UCAs when they undergo echocardiography. If their echocardiographic images are suboptimal, they may receive inappropriate diagnosis and treatment, or they may be referred for additional diagnostic testing, including radiation-based procedures that increase their lifetime risk for cancer or procedures that use contrast agents containing dye, which may increase the risk for kidney damage. An exhaustive review of current peer-reviewed research demonstrated no scientific basis for the UCA contraindication in patients with known or suspected cardiac shunts. Initial safety concerns were based on limited rodent data and speculation related to macroaggregated albumin microspheres, a radioactive nuclear imaging agent with different physical and chemical properties and no relation to UCAs. Radioactive macroaggregated albumin is not contraindicated in adult or pediatric patients with cardiac shunts and is routinely used in these populations. In conclusion, the International Contrast Ultrasound Society Board recommends removal of the contraindication to further the public interest in safe, reliable, radiation-free diagnostic imaging options for patients with known or suspected cardiac shunts and to reduce their need for unnecessary downstream testing.

In this study, we looked at the prognostic value of echocardiographic and hemodynamic measures in a large cohort of patients with precapillary pulmonary hypertension before and after initiation of treatment.Data were collected prospectively in a cohort of consecutive patients with precapillary pulmonary hypertension referred between 2002 and 2011. A range of clinical and echocardiographic variables were collected and stored on a database to assess predictors of survival. Invasive hemodynamic data including pulmonary artery pressure, pulmonary vascular resistance, capillary wedge pressure, and cardiac index were also obtained at baseline in all patients. Outcome was defined as mortality because of cardiovascular-related death. The study cohort comprised 777 patients (514 women) with precapillary pulmonary hypertension. A total of 195 (25%) died. In multivariable analysis, moderate or severe tricuspid regurgitation (hazard ratio [HR], 26.537; 95% confidence interval, 11.536-61.044; P<0.001), right ventricular myocardial performance index (HR, 3.421; 95% confidence interval, 1.777-6.584; P<0.001), and the presence of pericardial effusion (HR, 1.38; 95% confidence interval, 1.023-1.862; P=0.035) were independent predictors of mortality. High pulmonary vascular resistance and right atrial pressure by invasive hemodynamic measurements were independent predictors of mortality (HR, 1.084; 95% confidence interval, 1.041-1.130, and 1.079, respectively; 95% confidence interval, 1.049-1.111; P<0.001 for both), whereas patients with a higher cardiac index had better survival overall (HR, 0.384; 95% confidence interval, 0.307-0.481; P<0.001).Right ventricular dysfunction, moderate-severe tricuspid regurgitation, low cardiac index, and raised right atrial pressure were associated with poor survival for both pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertensive disease patients. The severity of tricuspid regurgitation, myocardial performance index, presence of pericardial effusion, pulmonary vascular resistance, cardiac index, and right atrial pressure may be used to stratify risk of death.