Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management.

Right ventricle assessment in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

INTRODUCTION: Limited data are available regarding the evaluation of right ventricular (RV) performance in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). OBJECTIVE: To evaluate the prevalence of RV dysfunction in patients with severe AS undergoing TAVI and long-term changes. METHODS: Consecutive patients with severe AS undergoing TAVI from January 2016 to July 2017 were included. RV anatomical and functional parameters were analyzed: RV diameters, fractional area change, tricuspid annular plane systolic excursion (TAPSE), S-wave tissue Doppler of the tricuspid annulus (RV-S'TDI), global longitudinal strain (RV-GLS), and free wall strain (RV-FWS). Preprocedure and 1-year echo were analyzed. RESULTS: Final population included 114 patients, mean age 83.63 ± 6.31 years, and 38.2% women. The prevalence of abnormal RV function was high, variable depending on the parameter that we analyzed, and it showed a significant reduction 1 year after TAVI implantation: 13.9% vs 6.8% (TAPSE < 17mm), P = .04; 26.3% vs 20% (fractional area change < 35%), P = .048; 41.2% vs 29.2% (RV-S'TDI < 9.5cm/s), P = .04; 48.7% vs 39.5% (RV-GLS > [20]), P = .049; and 48.7% vs 28.9% (RV-FWS > [20]), P = .03. Significant differences were noted between patients with low-flow (LF) vs normal-flow (NF) AS in RV dysfunction prevalence as well as in RV function recovery which is less evident in LF compared with NF patients. CONCLUSIONS: RV dysfunction is high among symptomatic AS patients undergoing TAVI, with variable prevalence depending on the echocardiographic parameter used.

Would the Use of Edoxaban Be Cost-effective for the Prevention of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation in Spain?

INTRODUCTION AND OBJECTIVES: To assess the cost-effectiveness of edoxaban vs acenocoumarol in the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in Spain. METHODS: Markov model, adapted to the Spanish setting from the perspective of the National Health System, stimulating the progression of a hypothetical cohort of patients with NVAF throughout their lifetime, with different health states: stroke, haemorrhage, and other cardiovascular complications. Efficacy and safety data were obtained from the available clinical evidence (mainly from the phase III ENGAGE AF-TIMI 48 study). The costs of managing NVAF and its complications were obtained from Spanish sources. RESULTS: Edoxaban use led to 0.34 additional quality-adjusted life years (QALY) compared with acenocoumarol. The incremental cost with edoxaban was 3916€, mainly because of higher pharmacological costs, which were partially offset by lower costs of treatment monitoring and managing NVAF events and complications. The cost per QALY was 11 518€, within the thresholds commonly considered cost-effective in Spain (25 000-30 000 €/QALY). The robustness of the results was confirmed by various sensitivity analyses. CONCLUSIONS: Edoxaban is a cost-effective alternative to acenocoumarol in the prevention of stroke and systemic embolism in patients with NVAF in Spain.

Innovative imaging methods in heart failure: a shifting paradigm in cardiac assessment. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology.

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.

Recomendações para Avaliação por Imagens das Próteses Valvares Cardíacas / Recommendations for the Imaging Assessment of Prosthetic Heart Valves

Disfunção de prótese valvar cardíaca (PVC) é rara, porém é uma potencial ameaça à vida. Estabelecer o exato mecanismo da disfunção da PVC é desafiador, no entanto é essencial para determinar a estratégia terapêutica apropriada. Na prática clinica, uma abordagem abrangente que integra vários parâmetros de morfologia e função avaliados pelo eco transtorácico 2D/3D e transesofágico são fundamentais para detectar e quantificar a disfunção da PVC. A cinefluoroscopia, a tomografia computadorizada com multidectetores, a ressonância magnética cardíaca, e em menor escala, a imagem nuclear, são ferramentas complementares para o diagnóstico e abordagem das complicações das PVC. Este documento apresenta recomendações para o uso de imagem em multimodalidade para avaliação das PVCs

Large-scale assessment of aortic stenosis: facing the next cardiac epidemic?

Aims: Aortic stenosis (AS) is the most frequent valvular disease in developed countries. As society grows older, the prevalence of AS increases. However, the real burden, current aetiology, severity distribution, and echocardiographic patterns of AS are not fully clear. The aim of the present study is to provide an accurate overall picture of AS, focusing on its epidemiology, aetiology, and echocardiographic features. Methods and results: A total of 29 502 consecutive echocardiograpies were prospectively included in this multicentre study. The present sample was composed of patients with advanced age (mean 75.2 years) and similar gender distribution. High proportion (7.2%) showed any grade of AS, with important number of patients (2.8%) presenting severe AS, most of them aged 75 years or more. Coexisting valvular disease appeared in almost half of the sample (49.6%), being the most frequently diagnosed aortic regurgitation (AR) (22%) followed by mitral regurgitation (MR) (15.6%). Degenerative aetiology was found in the vast majority (93.4%) of the studies whereas rheumatic is currently infrequent (3.35%). Low flow-low gradient (LFLG) appeared in 24.6% of patients with severe AS. Atrial fibrillation (23.1% vs. 11.6%; P = 0.002), MR (23.3% vs. 15.1%; P = 0.018), and right ventricle dysfunction (13.3% vs. 5.2%; P = 0.003) appeared frequently in LFLG group. Conclusions: Burden of AS is higher than previously assumed. Degenerative aetiology is the main cause of AS. Most of the patients are elder with high prevalence of significant co-existing valvular disease. LFLG severe AS is present in an important proportion of patients, showing high grade of left ventricle remodelling.

Reproducibility of a novel echocardiographic 3D automated software for the assessment of mitral valve anatomy.

BACKGROUND: 3D transesophageal echocardiography (TEE) is superior to 2D TEE in quantitative anatomic evaluation of the mitral valve (MV) but it shows limitations regarding automatic quantification. Here, we tested the inter-/intra-observer reproducibility of a novel full-automated software in the evaluation of MV anatomy compared to manual 3D assessment. METHODS: Thirty-six out of 61 screened patients referred to our Cardiac Imaging Unit for TEE were retrospectively included. 3D TEE analysis was performed both manually and with the automated software by two independent operators. Mitral annular area, intercommissural distance, anterior leaflet length and posterior leaflet length were assessed. RESULTS: A significant correlation between both methods was found for all variables: intercommissural diameter (r = 0.84, p < 0.01), mitral annular area (r = 0.94, p > 0, 01), anterior leaflet length (r = 0.83, p < 0.01) and posterior leaflet length (r = 0.67, p < 0.01). Interobserver variability assessed by the intraclass correlation coefficient was superior for the automatic software: intercommisural distance 0.997 vs. 0.76; mitral annular area 0.957 vs. 0.858; anterior leaflet length 0.963 vs. 0.734 and posterior leaflet length 0.936 vs. 0.838. Intraobserver variability was good for both methods with a better level of agreement with the automatic software. CONCLUSIONS: The novel 3D automated software is reproducible in MV anatomy assessment. The incorporation of this new tool in clinical MV assessment may improve patient selection and outcomes for MV interventions as well as patient diagnosis and prognosis stratification. Yet, high-quality 3D images are indispensable.

Recommendations for the imaging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography, and the Brazilian Department of Cardiovascular Imaging.

Prosthetic heart valve (PHV) dysfunction is rare but potentially life-threatening. Although often challenging, establishing the exact cause of PHV dysfunction is essential to determine the appropriate treatment strategy. In clinical practice, a comprehensive approach that integrates several parameters of valve morphology and function assessed with 2D/3D transthoracic and transoesophageal echocardiography is a key to appropriately detect and quantitate PHV dysfunction. Cinefluoroscopy, multidetector computed tomography, cardiac magnetic resonance imaging, and to a lesser extent, nuclear imaging are complementary tools for the diagnosis and management of PHV complications. The present document provides recommendations for the use of multimodality imaging in the assessment of PHVs.

[Cost-effectiveness analysis of apixaban versus acetylsalicylic acid in the prevention of stroke in patients with non-valvular atrial fibrillation in Spain]. / Análisis coste-utilidad de apixabán frente al ácido acetilsalicílico en la prevención del ictus en pacientes con fibrilación auricular no valvular en España.

OBJECTIVE: To assess the cost-effectiveness of apixaban versus acetylsalicylic acid (ASA) in stroke prevention in patients with non-valvular atrial fibrillation (NVAF) with contraindications of vitamin K antagonists in Spain. METHODS: A Markov model was adapted, simulating the patient's lifetime. The safety and efficacy of the drugs were obtained from AVERROES clinical trial. The analysis was done from the Spanish National Health System (NHS) and societal perspective. The cost of drugs was calculated according to the recommended doses. The cost of NVAF complications and disease management was obtained from Spanish sources. RESULTS: In a cohort of 1,000 patients with NVAF, during their lifetime numerous complications could be avoided with apixaban versus ASA (48 ischemic strokes, 10 systemic embolism and 53 related deaths). In each patient treated with apixaban more life-years (0.303 LYG) and more quality-adjusted life-years (0.277 QALYs) could be gained. Apixaban would generate more costs per patient for the NHS (€1,742 per patient) but savings would result from the social perspective (€2,887 saved per patient). The cost per LYG and QALY gained would be of €5,749 and €6,289 for the NHS. Apixaban would be dominant (more effective with less costs than ASA) from the societal perspective. The results were stable in both deterministic and probabilistic sensitivity analyses. CONCLUSIONS: According to this model, when costs and estimated lifetime outcomes achieved with apixaban are compared with those of ASA, apixaban was assessed to be a cost-effective treatment for the prevention of stroke in patients with NVAF in Spain.

Accuracy and reproducibility of novel echocardiographic three-dimensional automated software for the assessment of the aortic root in candidates for thanscatheter aortic valve replacement.

AIMS: A specialized three-dimensional transoesophageal echocardiography (3D-TOE) reconstruction tool has recently been introduced; the system automatically configures a geometric model of the aortic root from the images obtained by 3D-TOE and performs quantitative analysis of these structures. The aim of this study was to compare the measurements of the aortic annulus (AA) obtained by the new model to that obtained by 3D-TOE and multidetector computed tomography (MDCT) in candidates to transcatheter aortic valve implantation (TAVI) and to assess the reproducibility of this new method. METHODS AND RESULTS: We included 31 patients who underwent TAVI. The AA diameters and area were evaluated by the manual 3D-TOE method and by the automatic software. We showed an excellent correlation between the measurements obtained by both methods: intra-class correlation coefficient (ICC): 0.731 (0.508-0.862), r: 0.742 for AA diameter and ICC: 0.723 (0.662-0.923), r: 0.723 for the AA area, with no significant differences regardless of the method used. The interobserver variability was superior for the automatic measurements than for the manual ones. In a subgroup of 10 patients, we also found an excellent correlation between the automatic measurements and those obtained by MDCT, ICC: 0.941 (0.761-0.985), r: 0.901 for AA diameter and ICC: 0.853 (0.409-0.964), r: 0.744 for the AA area. CONCLUSION: The new automatic 3D-TOE software allows modelling and quantifying the aortic root from 3D-TOE data with high reproducibility. There is good correlation between the automated measurements and other 3D validated techniques. Our results support its use in clinical practice as an alternative to MDCT previous to TAVI.

Cost-effectiveness Analysis Comparing Apixaban and Acenocoumarol in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation in Spain.

INTRODUCTION AND OBJECTIVES: Cost-effectiveness analysis of apixaban (5 mg twice daily) vs acenocoumarol (5mg/day) in the prevention of stroke in patients with nonvalvular atrial fibrillation in Spain. METHODS: Markov model covering the patient's entire lifespan with 10 health states. Data on the efficacy and safety of the drugs were provided by the ARISTOTLE trial. Warfarin and acenocoumarol were assumed to have therapeutic equivalence. PERSPECTIVES: The Spanish National Health System and society. Information on the cost of the drugs, complications, and the management of the disease was obtained from Spanish sources. RESULTS: In a cohort of 1000 patients with nonvalvular atrial fibrillation, administration of apixaban rather than acenocoumarol would avoid 18 strokes, 71 hemorrhages (28 intracranial or major), 2 myocardial infarctions, 1 systemic embolism, and 23 related deaths. Apixaban would prolong life (by 0.187 years) and result in more quality-adjusted life years (by 0.194 years) per patient. With apixaban, the incremental costs for the Spanish National Health System and for society would be € 2,488 and € 1,826 per patient, respectively. Consequently, the costs per life year gained would be € 13,305 and € 9,765 and the costs per quality-adjusted life year gained would be € 12,825 and € 9,412 for the Spanish National Health System and for society, respectively. The stability of the baseline case was confirmed by sensitivity analyses. CONCLUSIONS: According to this analysis, apixaban may be cost-effective in the prevention of stroke in patients with nonvalvular atrial fibrillation compared with acenocoumarol.

Efficiency of naproxen/esomeprazole in association for osteoarthrosis treatment in Spain.

OBJECTIVE: To assess, from the perspective of the National Healthcare System, the efficiency of a fixed-dose combination of naproxen and esomeprazole (naproxen/esomeprazole) in the treatment of osteoarthritis (OA) compared to other NSAID, alone or in combination with a proton pump inhibitor (PPI). METHODS: A Markov model was used; it included different health states defined by gastrointestinal (GI) events: dyspepsia, symptomatic or complicated ulcer; or cardiovascular (CV) events: myocardial infarction, stroke or heart failure. The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008. The total costs (€, 2012), including drug and event-related costs, and the health outcomes expressed in quality-adjusted life years (QALY) were estimated in patients with increased GI risk, aged 65 or over, for a 1-year time horizon and a 6-month treatment with celecoxib (200mg/day), celecoxib+PPI, diclofenac (150mg/day)+PPI, etoricoxib (60mg/day), etoricoxib+PPI, ibuprofen (1,800mg/day)+PPI, naproxen (1,000mg/day)+PPI or naproxen/esomeprazole (naproxen 1,000mg/esomeprazole 40mg/day). The selected PPI was omeprazole (20mg/day). RESULTS: Naproxen/esomeprazole was a dominant strategy (more effective and less costly) compared to celecoxib, etoricoxib and diclofenac+PPI. Celecoxib+PPI and etoricoxib+PPI were more effective. Considering a cost-effectiveness threshold of €30,000 per additional QALY, naproxen/esomeprazole was cost-effective compared to ibuprofen+PPI and naproxen+PPI with incremental cost-effectiveness ratios (ICER) of €15,154 and €5,202 per additional QALY, respectively. CONCLUSIONS: A fixed-dose combination of naproxen and esomeprazole is a cost-effective, and even dominant, alternative compared to other options in OA patients with increased GI risk.

Effectiveness of three sleep apnea management alternatives.

RATIONALE: Home respiratory polygraphy (HRP) may be a cost-effective alternative to polysomnography (PSG) for diagnosis and treatment election in patients with high clinical probability of obstructive sleep apnea (OSA), but there is conflicting evidence on its use for a wider spectrum of patients. OBJECTIVES: To determine the efficacy and cost of OSA management (diagnosis and therapeutic decision making) using (1) PSG for all patients (PSG arm); (2) HRP for all patients (HRP arm); and (3) HRP for a subsample of patients with high clinical probability of being treated with continuous positive airway pressure (CPAP) and PSG for the remainder (elective HRP arm). METHODS: Multicentric study of 366 patients with intermediate-high clinical probability of OSA, randomly subjected to HRP and PSG. We explored the diagnostic and therapeutic decision agreements between the PSG and both HRP arms for several HRP cutoff points and calculated costs for equal diagnostic and/or therapeutic decision efficacy. RESULTS: For equal diagnostic and therapeutic decision efficacy, PSG arm costs were 18% higher than HRP arm costs and 20% higher than elective HRP arm costs. HRP arm costs tended to be lower than elective HRP arm costs, and both tended to be lower than PSG arm costs if patient costs were omitted. CONCLUSION: Home respiratory polygraphy is a less costly alternative than polysomnography for the diagnosis and therapeutic decision making for patients with suspected obstructive sleep apnea. We found no advantage in cost terms, however, in using home respiratory polygraphy for all patients or home respiratory polygraphy for the most symptomatic patients and polysomnography for the rest.

Patient perspective on the management of atrial fibrillation in five European countries.

BACKGROUND: Long-term management of chronic conditions, such as atrial fibrillation (AF), require frequent interactions with the healthcare systems. The multinational EUropean Patient Survey in Atrial Fibrillation (EUPS-AF) was conducted to investigate patient satisfaction with AF management in different of five European healthcare systems at a time of changing treatment paradigms for stroke prophylaxis, prior to the advent of newer oral anticoagulants. METHODS: Adults (>18 years) were recruited at random from the total populations of France, Germany, Italy, Spain and the UK using a randomized telephone dialling system. At least 300 respondents per country reporting to have a diagnosis of AF or receiving oral anticoagulation therapy for suspected AF or to have a heart rhythm disturbance completed a structured telephone interview. RESULTS: Most respondents were satisfied with their treatment for AF over the previous 12 months, with 85.5% (n = 1289) rating their care as good or better. Suboptimal clinical practices, however, were identified in several key areas. Coordination of primary and secondary care and a lack of patient engagement and support were particular issues, especially for those patients likely to have extensive contact with their healthcare system. CONCLUSIONS: In the context of Europe-wide guidelines for management of AF, most patients with AF were satisfied with their care, but for a greater proportion of patients, some aspects are unsatisfactory. Patient-centred surveys, such as the EUPS-AF, are crucial for understanding the factors that contribute to patient satisfaction and compliance with long-term treatment for chronic conditions.

Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging.

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Echocardiography has become the primary non-invasive imaging method for the evaluation of valvular regurgitation. The echocardiographic assessment of valvular regurgitation should integrate the quantification of the regurgitation, assessment of the valve anatomy and function, as well as the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation thus largely integrates the results of echocardiography. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing regurgitation.

3D color-Doppler echocardiography and chronic aortic regurgitation: a novel approach for severity assessment.

BACKGROUND: 3D echocardiography provides a complete evaluation of the aortic valve and adjacent structures and it improves the assessment of this cardiac region. Three-dimensional color-Doppler echocardiography (3DCDE) evaluation might improve the measurements of the functional regurgitant orifice in patients with Chronic Aortic Regurgitation (CAR). OBJECTIVES: Our aim was to compare the accuracy of current echo-Doppler methods and 3DCDE for the assessment of CAR severity. The reference method used in this work was the CAR severity determined by means of cardiac magnetic resonance (CMR) METHODS: Thirty-two consecutive patients with an established diagnosis of CAR recruited in our institution comprised our study group. CAR severity was determined by conventional Echo-Doppler methods and by 3DCDE and their results were compared with those obtained by means of CMR. RESULTS: Mean age was 63.0 ± 13.5 years. Twenty-two patients (68.8%) were men. Compared with the traditional echo-Doppler methods, 3DCDE evaluation had the best linear association with CMR results (3D vena contracta cross sectional area method: r = 0.88; r square = 0.77; p < 0.001. 3D vena contracta cross sectional area/left ventricular outflow tract cross sectional area method: r = 0.87; r square = 0.75; p < 0.001). The ROC analysis showed an excellent area under curve for detection of severe CAR (3D vena contracta cross sectional area method = 0.97; 3D vena contracta cross sectional area/left ventricular outflow tract cross sectional area method = 0.98). Inter- and intra-observer variability for the 3DCDE evaluation was good (ICC = 0.89 and ICC = 0.91 for inter and intra observer variability respectively). CONCLUSIONS: 3DCDE is an accurate and highly reproducible diagnostic tool for estimating CAR severity. Compared with the traditional echo-Doppler methods, 3DCDE has the best agreement with the CMR determined CAR severity. Thus, 3DCDE is a diagnostic method that may improve the therapeutic management of patients with CAR.