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Mitral annular disjunction (MAD), a separation between the left atrium/mitral valve annulus and the left ventricular myocardium, is frequently seen in patients with arrhythmic mitral valve prolapse. Although an association exists between MAD and ventricular arrhythmias, little is known regarding the identification of individuals at high risk. Multimodality imaging including echocardiography, computed tomography, cardiac magnetic resonance, and positron emission tomography can play an important role in both the diagnosis and risk stratification of MAD. Due to a paucity of data, clinical decision making in a patient with MAD is challenging and remains largely empirical. Although MAD itself can be corrected surgically, the prevention and treatment of associated arrhythmias may require medical therapy, catheter ablation, and an implantable cardioverter-defibrillator. Prospective data are required to define the role of implantable cardioverter-defibrillators, targeted catheter ablation, and surgical correction in selected, at-risk patients., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology of Leiden University Medical Center has received research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Dr Stassen has received grants from the European Society of Cardiology (Training Grant App000064741). Dr Haugaa has received grants from the Norwegian Research Council (ProCardio #309762, #288438, #298736). Dr Faletra has received speaker fees from Philips Healthcare. Dr Enriquez-Sarano has received consulting fees from Artivion, ChemImage, Edwards Lifesciences, and HighLife. Dr Marsan has received speaker fees from Abbott Vascular and GE Healthcare. Dr Bax has received speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Lifestyle interventions are recommended as the first-line treatment to control metabolic syndrome components and improve cardiometabolic risk factors. However, studies directly comparing the cardiometabolic effects of the Dietary Approaches to Stop Hypertension (DASH) vs. the Mediterranean diet (MedDiet) accompanied by salt restriction are currently lacking. Thus, with the present secondary analyses of a randomized trial, we aimed to assess the cardiometabolic effects of a 3-month intensive dietary intervention implementing salt restriction alone or on top of the DASH and MedDiet compared to no/minimal intervention in never drug-treated adults with high normal blood pressure (BP) or grade 1 hypertension., Methods: We randomly assigned individuals to the control group (CG, n = 60), salt restriction group (SRG, n = 60), DASH diet with salt restriction group (DDG, n = 60), or MedDiet with salt restriction group (MDG, n = 60)., Results: According to the intention-to-treat analysis, the DDG and the MDG had lower odds ratio (OR) (95% CI) of metabolic syndrome [0.29 (0.12, 0.72), and 0.15 (0.06, 0.41), respectively] compared to the CG. Moreover, the MDG had lower odds of metabolic syndrome compared to the SRG and lower odds of elevated BP levels than the DDG and the SRG. Moreover, total and LDL-cholesterol, fasting glucose, HbA1c, and systolic/diastolic BP were reduced in all three intervention groups compared to the CG., Conclusion: On a background of salt restriction, the MedDiet was superior in BP reduction, but the DASH and MedDiet reduced the prevalence of metabolic syndrome to the same extent., Competing Interests: Conflicts of interest None related to the present work for all authors., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Aims: Left ventricular ejection fraction (LVEF) calculation by echocardiography is pivotal in evaluating cancer patients' cardiac function. Artificial intelligence (AI) can facilitate the acquisition of optimal images and automated LVEF (autoEF) calculation. We sought to evaluate the feasibility and accuracy of LVEF calculation by oncology staff using an AI-enabled handheld ultrasound device (HUD)., Methods and Results: We studied 115 patients referred for echocardiographic LVEF estimation. All patients were scanned by a cardiologist using standard echocardiography (SE), and biplane Simpson's LVEF was the reference standard. Hands-on training using the Kosmos HUD was provided to the oncology staff before the study. Each patient was scanned by a cardiologist, a senior oncologist, an oncology resident, and a nurse using the TRIO AI and KOSMOS EF deep learning algorithms to obtain autoEF. The correlation between autoEF and SE-ejection fraction (EF) was excellent for the cardiologist ( r = 0.90), the junior oncologist ( r = 0.82), and the nurse ( r = 0.84), and good for the senior oncologist ( r = 0.79). The Bland-Altman analysis showed a small underestimation by autoEF compared with SE-EF. Detection of impaired LVEF < 50% was feasible with a sensitivity of 95% and specificity of 94% for the cardiologist; sensitivity of 86% and specificity of 93% for the senior oncologist; sensitivity of 95% and specificity of 91% for the junior oncologist; and sensitivity of 94% and specificity of 87% for the nurse., Conclusion: Automated LVEF calculation by oncology staff was feasible using AI-enabled HUD in a selected patient population. Detection of LVEF < 50% was possible with good accuracy. These findings show the potential to expedite the clinical workflow of cancer patients and speed up a referral when necessary., Competing Interests: Conflict of interest: This study was performed with a loan of handheld ultrasound devices and technical support by Echonous Inc., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies., Competing Interests: The authors declare no conflict of interest.

Background: The aim of this study was to evaluate the ability of a novel handheld echocardiography (HHE) device with continuous-wave Doppler (CWD) capability to measure aortic valve peak jet velocity (Vmax) and facilitate aortic stenosis (AS) severity grading., Methods: One hundred twenty-one consecutive patients with known or suspected AS were prospectively included. All patients were scanned with the HHE device and a high-end echocardiography system (the reference standard) to obtain CWD signal across the aortic valve. Aortic Vmax measurements were acquired from the apical five-chamber view using both methods and were compared to assess method agreement using the intraclass correlation coefficient, linear regression analysis, and Bland-Altman analysis. Diagnostic accuracy for the detection of at least moderate AS (Vmax ≥ 3 m/sec) was calculated. Also, the utility of HHE with CWD to reclassify patients compared with the visual estimation of AS severity was assessed., Results: The acquisition of CWD signal using HHE was feasible in 118 of 121 patients (mean age, 68 ± 17 years; 57% men). There was excellent agreement between the HHE CWD and the cart-based measurements (intraclass correlation coefficient = 0.97 [95% CI: 0.83-0.99] and r = 0.98 [95% CI: 0.91-0.99], P < .001 for both). The Bland-Altman plot showed a small underestimation bias of -0.2 m/sec (P < .001), with limits of agreement ±0.44 m/sec for Vmax. Detection of at least moderate AS using HHE with CWD was feasible with sensitivity of 93% (95% CI: 83%-98%), specificity of 98% (95% CI: 91%-100%), positive predictive value of 98% (95% CI: 88%-100%), negative predictive value of 94% (95% CI: 85%-97%), and total diagnostic accuracy of 96%. Patients visually assessed as having mild AS were reclassified as having no stenosis (17%), mild AS (72%), or moderate AS (11%) with the addition of CWD imaging., Conclusions: Use of a novel HHE device with CWD spectral analysis by experienced operators can reliably detect clinically significant AS and facilitate AS grading. This technology may improve screening and diagnostic workup of AS compared with current practice., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The present CEUS Cardiac Exam Protocols represent the first effort to promulgate a standard set of protocols for optimal administration of ultrasound enhancing agents (UEAs) in echocardiography, based on more than two decades of experience in the use of UEAs for cardiac imaging. The protocols reflect current clinical CEUS practice in many modern echocardiography laboratories throughout the world. Specific attention is given to preparation and dosing of three UEAs that have been approved by the United States Food and Drug Administration (FDA) and additional regulatory bodies in Europe, the Americas and Asia-Pacific. Consistent with professional society guidelines (J Am Soc Echocardiogr 31:241-274, 2018; J Am Soc Echocardiogr 27:797-810, 2014; Eur Heart J Cardiovasc Imaging 18:1205, 2017), these protocols cover unapproved "off-label" uses of UEAs-including stress echocardiography and myocardial perfusion imaging-in addition to approved uses. Accordingly, these protocols may differ from information provided in product labels, which are generally based on studies performed prior to product approval and may not always reflect state of the art clinical practice or guidelines., (© 2022. The Author(s).)

The 35th Annual Advances in Contrast Ultrasound International Bubble Conference convened in Chicago, IL, USA, on September 30th to October 1st, 2021. It featured a range of novel research from animal studies to clinical applications in multiple organ systems, demonstrating the utility of contrast enhanced ultrasound (CEUS). A multidisciplinary group of experts on the use of CEUS, including physicians, basic scientists, engineers, and industry partners, convened to discuss cutting edge research and new applications for CEUS. The conference demonstrated the wide range of CEUS uses and potential uses, including cardiac risk stratification, sonothrombolysis, peripheral vascular reperfusion, liver and renal mass evaluation, lymphatic evaluation, sentinel node identification, and CEUS use in pediatrics. The International Contrast Ultrasound Society uses this information to continue advocating for the safe and appropriate use of CEUS., (© 2022. The Author(s).)

We compared speckle tracking echocardiography (STE) and feature tracking cardiovascular magnetic resonance (FT-CMR) in patients with hypertrophic cardiomyopathy (HC) with a varying extent of fibrosis as defined by late gadolinium enhancement to look at the level of agreement between methods and their ability to relate those to myocardial fibrosis. At 2 reference centers, 79 patients with HC and 16 volunteers (the control group) underwent STE and CMR with late gadolinium enhancement and FT-CMR. Patients were classified into 3 categories: no detectable, limited, and extensive fibrosis. Global longitudinal strain (GLS) and global radial strain (GRS) were derived using FT-CMR and STE. STE-derived GRS was decreased in all HC categories compared with the control group (p <0.001), whereas FT-CMR GRS was reduced only in patients with HC with fibrosis (p <0.05). Reduced STE-derived GLS was associated with extensive fibrosis (p <0.05) and a value less than -15.2% identified those with extensive fibrosis (sensitivity 79%, specificity 92%, area under the curve 0.863, 95% confidence interval [CI] 0.76 to 0.97, p <0.001). Inter-modality agreement was moderate for STE versus CMR-GLS (overall population intra-class correlation coefficient = 0.615, 95% CI 0.42 to 0.75, p <0.001; patients with HC 0.63, 0.42 to 0.76, p <0.001) and GRS (overall population intra-class correlation coefficient = 0.601, 95% CI 0.397 to 0.735, p <0.001). A low level of agreement for GRS was seen between methods in patients with HC. In conclusion, strain indexes measured using echocardiography and CMR are reduced in patients with HC compared with the control group and correlate well with the burden of myocardial fibrosis. Reduced STE-GLS can identify patients with extensive fibrosis, but whether there is an added value for risk stratification for sudden cardiac death remains to be determined., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To evaluate the association between baseline global longitudinal strain (GLS) and ΔGLS (difference of baseline GLS and follow-up) and cardiac resynchronization therapy (CRT) response defined either with clinical or with echocardiographic characteristics. This meta-analysis was performed in accordance to both the Meta-Analysis of Observational Studies in Epidemiology and Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Two independent investigators performed a comprehensive systematic search in MedLine, EMBASE and Cochrane databases through September 2019 without limitations. Data analysis was performed by using the Review Manager software (RevMan), version 5.3, and Stata 13 software. A p value of less than 0.05 (two-tailed) was considered statistically significant. Twelve studies (1004 patients, mean age 63.8 years old, males 69.4%) provided data on the association of baseline GLS with the response to CRT therapy. We found that CRT responders had significantly better resting GLS values compared with non-responders [GLS mean difference -2.13 (-3.03, -1.23), p < 0.001, I 2 78%]. Furthermore, CRT responders had significantly greater improvement of GLS at follow-up compared with non-responders [ΔGLS mean difference -3.20 (-4.95, -1.45), p < 0.001, I 2 66%]. These associations remained significant in a subgroup analysis including only studies with similar CRT response definition. In this meta-analysis, we found that CRT responders had a baseline and ΔGLS significantly higher than the non-responders strengthening the central role of GLS as a tool for selecting candidates for CRT. Furthermore, improved GLS values after CRT may be used to better define CRT responders., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stress echocardiography (SE) is a well established and valid technique, widely used for the diagnostic evaluation of patients with ischemic and nonischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of present medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training-which focus on the preparation, the protocols used, the analysis of the SE images, and updated, evidence-based knowledge about SE applications on ischemic and nonischemic heart diseases, such as in cardiomyopathies, heart failure, and valvular heart disease., (Copyright © 2021 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Aims: Currently there are scarce epidemiological data regarding prevalence, clinical phenotype, and therapy of hypertensive urgencies (HU) and emergencies (HE). The aim of this article was to record the prevalence, clinical characteristics, and management of patients with HU and HE assessed in an emergency department (ED) of a tertiary hospital., Methods and Results: The population consisted of patients presenting with HE and HU in the ED (acute increase in systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥120 mmHg with and without acute target organ damage, respectively). Of the 38 589 patients assessed in the ED during a 12-month period, 353 (0.91%) had HU and HE. There were 256 (72.5%) cases presented as HU and 97 (27.5%) as HE. Primary causes for both HU and HE were stress/anxiety (44.9%), increased salt intake (33.9%), and non-adherence to medication (16.2%). Patients with HU reported mainly dizziness/headache (46.8%) and chest pain (27.4%), whereas those with HE presented dyspnoea (67%), chest pain (30.2%), dizziness/headache (10.3%), and neurological disorders (8.2%). In HE, the underlying associated conditions were pulmonary oedema (58%), acute coronary syndrome (22.6%), and neurological disorders/stroke (7.2%). All HE cases were hospitalized and received intensive healthcare, including dialysis., Conclusion: This 1-year single-centre registry demonstrates a reasonable prevalence of HU and HE contributing to the high volume of visits to the ED. Stress, increased salt intake and non-adherence were main triggers of HE and HU. Dizziness and headache were the prevalent symptoms of HU patients while heart failure was the most common underlying disease in patients with HE., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: We sought to evaluate the reliability and diagnostic accuracy of a novel handheld ultrasound device (HUD) with artificial intelligence (AI) assisted algorithm to automatically calculate ejection fraction (autoEF) in a real-world patient population., Methods and Results: We studied 100 consecutive patients (57 ± 15 years old, 61% male), including 38 with abnormal left ventricular (LV) function [LV ejection fraction (LVEF) < 50%]. The autoEF results acquired using the HUD were independently compared with manually traced biplane Simpson's rule measurements on cart-based systems to assess method agreement using intra-class correlation coefficient (ICC), linear regression analysis, and Bland-Altman analysis. The diagnostic accuracy for the detection of LVEF <50% was also calculated. Test-retest reliability of measured EF by the HUD was assessed by calculating the ICC and the minimal detectable change (MDC). The ICC, linear regression analysis, and Bland-Altman analysis revealed good agreement between autoEF and reference manual EF (ICC = 0.85; r  = 0.87, P  < 0.001; mean bias -1.42% with limits of agreement 14.5%, respectively). Detection of abnormal LV function (EF < 50%) by autoEF algorithm was feasible with sensitivity 90% (95% CI 75-97%), specificity 87% (95% CI 76-94%), PPV 81% (95% CI 66-91%), NPV 93% (95% CI 83-98%), and a total diagnostic accuracy of 88%. Test-retest reliability was excellent (ICC = 0.91, P  < 0.001; r  = 0.91, P  < 0.001; mean difference ± SD: 0.54% ± 5.27%, P  = 0.308) and MDC for LVEF measurement by autoEF was calculated at 4.38%., Conclusion: Use of a novel HUD with AI-enabled capabilities provided similar LVEF results with those derived by manual biplane Simpson's method on cart-based systems and shows clinical potential., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Despite considerable advances in pharmacological treatments, hypertension remains a major cause of premature morbidity and mortality worldwide since elevated blood pressure (BP) adversely influences cardiovascular and renal outcomes. Accordingly, the current hypertension guidelines recommend the adoption of dietary modifications in all subjects with suboptimal BP levels. These modifications include salt intake reduction and a healthy diet, such as the Dietary Approaches to Stop Hypertension (DASH) diet or the Mediterranean diet (MedDiet), independently of the underlying antihypertensive drug treatment. However, dietary modifications for BP reduction in adults with prehypertension or hypertension are usually examined as stand-alone interventions and, to a lesser extent, in combination with other dietary changes. The purpose of the present review was to summarize the evidence regarding the BP effect of salt restriction in the context of the DASH diet and the MedDiet. We also summarize the literature regarding the effects of these dietary modifications when they are applied as the only intervention for BP reduction in adults with and without hypertension and the potent physiological mechanisms underlying their beneficial effects on BP levels. Available data of randomized controlled trials (RCTs) provided evidence about the significant BP-lowering effect of each one of these dietary strategies, especially among subjects with hypertension since they modulate various physiological mechanisms controlling BP. Salt reduction by 2.3 g per day in the DASH diet produces less than half of the effect on systolic blood pressure (SBP)/diastolic blood pressure (DBP) (-3.0/-1.6 mmHg) as it does without the DASH diet (-6.7/-3.5 mmHg). Although their combined effect is not fully additive, low sodium intake and the DASH diet produce higher SBP/DBP reduction (-8.9/-4.5 mmHg) than each of these dietary regimens alone. It is yet unsettled whether this finding is also true for salt reduction in the MedDiet., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Objectives: The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM)., Background: Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD)., Methods: A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death., Results: MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk)., Conclusions: Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM., Competing Interests: Funding Support and Author Disclosures This program was funded by Barts Charity grant 1107/2356/MRC0140 to Dr Captur. Dr Captur is supported by British Heart Foundation Special Programme Grant MyoFit46 (SP/20/2/34841), the National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration, and the NIHR UCL Hospitals Biomedical Research Center. Dr Petersen has received support from the Barts Biomedical Research Centre, funded by the NIHR. Dr Moon is directly and indirectly supported by the UCL Hospitals NIHR BRC and Biomedical Research Unit at Barts Hospital, respectively. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) is a highly prevalent clinical syndrome characterized by considerable phenotypic heterogeneity. The traditional classification based on left ventricular ejection fraction (LVEF) is widely accepted by the guidelines and represents the grounds for patient enrollment in clinical trials, even though it shows several limitations. Ejection fraction (EF) is affected by preload, afterload, and contractility, it being problematic to express LV function in several conditions, such as HF with preserved EF (HFpEF), valvular heart disease, and subclinical HF, and in athletes. Over the last two decades, developments in diagnostic techniques have provided useful tools to overcome EF limitations. Strain imaging analysis (particularly global longitudinal strain (GLS)) has emerged as a useful echocardiographic technique in patients with HF, as it is able to simultaneously supply information on both systolic and diastolic functions, depending on cardiac anatomy and physiology/pathophysiology. The use of GLS has proved helpful in terms of diagnostic performance and prognostic value in several HF studies. Universally accepted cutoff values and variability across vendors remain an area to be fully explored, hence limiting routine application of this technique in clinical practice. In the present review, the current role of GLS in the diagnosis and management of patients with HF will be discussed. We describe, by critical analysis of the pros and cons, various clinical settings in HF, and how the appropriate use and interpretation of GLS can provide important clues., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

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., Competing Interests: Conflict of interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

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<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., Competing Interests: Competing interests: GWM is director of annual Imperial Valve and Cardiovascular Course (IVCC) which receives support from industry companies. She is also a director of an international fellowship supported by Abbott Vascular between Imperial Healthcare NHS trust, Villa Maria Cecilia Hospital GVM and Columbus Hospital Italy. RA-L has received speaker honorarium from Phillips Volcano., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the incidence, predictors and outcomes of female patients with patient-prosthesis mismatch (PPM) following transcatheter aortic valve intervention (TAVI) for severe aortic stenosis (AS)., Background: Female AS TAVI recipients have a significantly lower mortality than surgical aortic valve replacement (SAVR) recipients, which could be attributed to the potentially lower PPM rates. TAVI has been associated with lower rates of PPM compared to SAVR. PPM in females post TAVI has not been investigated to date., Methods: The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry is a multicenter registry of women undergoing TAVR for severe symptomatic AS. Two hundred and fifty patients with detailed periprocedural and follow-up echocardiographic investigations were included in the WIN-TAVI echocardiographic sub-study. PPM was defined as per European guidelines stratified by the presence of obesity., Results: The incidence of PPM in our population was 32.8%. Patients with PPM had significantly higher BMI (27.4 ± 6.1 vs. 25.2 ± 5.0, p = .002), smaller sized valves implanted (percentage of TAVI ≤23 mm 61% vs. 29.2%, PPM vs. no PPM, p < .001) and were more often treated with balloon expandable valves (48.3 vs. 32.5%, p < .001) rather than self expanding ones (26.3 vs. 52.8%, <.001). BMI (OR = 1.08; 95%CI 1.02-1.14, p = .011) and valve size ≤23 mm (OR = 3.00 95%CI 1.14-7.94, p = .027) were the only independent predictors of PPM. There was no significant interaction between valve size and valve type (p = .203). No significant differences were observed in 1-year mortality or major adverse cardiovascular events., Conclusions: PPM in females undergoing TAVI occurs in one third of patients. BMI and valve size ≤23 mm are independent predictors. Larger registries are required to determine the impact of PPM on future clinical outcomes., (© 2020 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Objective: Pregnancy in women with aortic coarctation (CoA) has an estimated moderately increased risk (mWHO II-III) of adverse cardiovascular, obstetric or fetal events, but prospective data to validate this risk classification are scarce. We examined pregnancy outcomes and identified associations with adverse outcomes., Methods: Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=303 out of 5739), part of the European Society of Cardiology EURObservational Research Programme. The frequency of and associations with major adverse cardiac events (MACE) and hypertensive disorders (pregnancy-induced hypertension, (pre-)eclampsia or haemolysis, elevated liver enzymes and low platelets syndrome) were analysed., Results: Of 303 pregnancies (mean age 30 years, pregnancy duration 39 weeks), 9.6% involved unrepaired CoA and 27.1% were in women with pre-existing hypertension. No maternal deaths or aortic dissections occurred. MACE occurred in 13 pregnancies (4.3%), of which 10 cases were of heart failure (3.3%). Univariable associations with MACE included prepregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8 to 147.7), left ventricular ejection fraction <40% (OR 10.4, 95% CI 1.8 to 59.5), New York Heart Association class >1 (OR 11.4, 95% CI 3.6 to 36.3) and cardiac medication use (OR 4.9, 95% CI 1.3 to 18.3). Hypertensive disorders of pregnancy occurred in 16 (5.3%), cardiac medication use being their only predictor (OR 3.2, 95% CI 1.1 to 9.6). Premature births were 9.1%, caesarean section was performed in 49.7% of pregnancies. Of 4 neonatal deaths, 3 were after spontaneous extreme preterm birth., Conclusions: The ROPAC data show low MACE and hypertensive disorder rates during pregnancy in women with CoA, suggesting pregnancy to be more safe and better tolerated than previously appreciated., Competing Interests: Competing interests: KPR, DT, MG, MS, LB, AY, PN, PM, EB, MRJ, RH and JWR-H have nothing to disclose. APM reports personal fees from Bayer, Fresenius, Novartis outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2020 European Society of Cardiology.)

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., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Aims: To assess left ventricular (LV) function before and after transcatheter aortic valve implantation (TAVI) using conventional echocardiographic parameters and global longitudinal LV strain (GLS) and compare outcomes between Edwards S3 and Evolut R valves., Methods and Results: Data were collected for consecutive patients undergoing TAVI at Hammersmith hospital between 2015 and 2018. Of the 303 patients, those with coronary artery disease and atrial fibrillation were excluded leading to a total of 85 patients, which constituted our study group. The mean follow-up was 49 ± 39 days. In total, 60% of patients were treated with Edwards S3 and 40% Evolut R. TAVI resulted in an early improvement of GLS (-13.96 to -15.25%, P = 0.01) but not ejection fraction (EF) (47.6 to 50.1%, P = 0.09). LV mass also improved, especially in patients with marked baseline LV hypertrophy (P < 0.001). There were no appreciable differences of LV function improvement and overall LV remodelling after TAVI between the two types of valves used (P = 0.14)., Conclusions: TAVI results in reverse remodelling and improvement of GLS, especially in patients with impaired baseline LV function. There were no differences in the extent of LV function improvement between Edwards S3 and Evolut R valves but there was a greater incidence of aortic regurgitation with Evolut R., (© 2020. The authors.)

Preeclampsia at term accounts for half of maternal deaths from hypertensive disorders. We aimed to assess differences in maternal cardiac indices at 35 +0 to 36 +6 weeks' gestation between women who subsequently developed preeclampsia at term compared with those with uncomplicated pregnancy and to evaluate whether cardiac indices offer incremental prognostic value to the available screening algorithm for preeclampsia. We recruited 1602 women with singleton pregnancies who attended for a routine hospital visit at 35 +0 to 36 +6 weeks' gestation between April and November 2018. We recorded maternal characteristics and preeclampsia-risk-score derived from a competing risks model and measured cardiac indices. Preeclampsia developed in 3.12% (50/1602) of participants. Women with preeclampsia, compared with those without, had increased mean arterial pressure (97.6, SD, 5.53 versus 87.9, SD, 6.82 mm Hg), systemic vascular resistance (1500, interquartile range, 1393-1831 versus 1400, interquartile range, 1202-1630 PRU) and preeclampsia-risk-score (23.4, interquartile range, 9.13-40 versus 0.9, interquartile range, 0.32-3.25). Multivariable analysis demonstrated independent association between the incidence of preeclampsia and E/e' (hazard ratio, 1.19/unit [95% CI, 1.03-1.37]; P =0.018) as well as left ventricular mass indexed for body surface area (hazard ratio, 1.03/[g·m 2 ] [95% CI, 1.003-1.051]; P =0.029). Women with E/e' ≥7.3 and left ventricular mass indexed for body surface area ≥63.2 g/m 2 had an increased risk for developing preeclampsia, despite low preeclampsia-risk-score <5% (hazard ratio, 20.1 [95% CI, 10.5-38.7], P <0.001). Increased left ventricular mass and E/e' offer incremental information to available scoring systems and better stratify women at risk of developing preeclampsia at term.

Background: Compensatory remodelling i.e. increased right ventricular (RV) mass frequently occurs as an adaptive response to the chronic pressure overload to maintain contractile function. The prognostic value of the serial change in RV mass is unclear., Aim: The aim of our study was to examine the longitudinal changes in RV mass and survival in patients with idiopathic pulmonary arterial hypertension (IPAH)., Methods: Consecutive newly diagnosed IPAH patients >18 years old were prospectively recruited from a tertiary referral center. All recruited patients were maintained on guideline-based therapy and were followed up with echocardiography and cardiac magnetic resonance for 2 years., Results: Serial measures of RV mass revealed that survivors appeared to have had a compensatory increase in RV mass, which constituted adaptive RV remodelling early in the disease process, which was not seen in those who died. (Hazard ratio of 0.932, 95% confidence interval 0.893-0.973, p = 0.001)., Conclusion: This study shows that serial measurement of RV mass in IPAH patients provides prognostic information. RV mass regression is an ominous prognostic sign, which may predict early mortality in these patients., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: It is unknown whether ethnic differences occur with regard to right heart echocardiographic parameters. The aim of this study therefore was to establish normative values of left and right heart parameters in a black African population and to evaluate the effect of age and body mass index (BMI) on specific right ventricle (RV) parameters., Methods: Two hundred fifty-three normal subjects were prospectively studied. A standardized echocardiographic examination was conducted with the RV focused view used to derive RV measurements. All left and right heart measurements were made in accordance with the American Society of Echocardiography 2015 chamber guideline recommendations. Right ventricle free wall strain was assessed using an RV focused apical four-chamber view., Results: The average age was 36.3 ± 12.2 years, and 59% of patients were female. The mean left ventricular ejection fraction was 62.3% ± 5.7%. The RV linear measurements (RV base, 31.0 ± 4.5 mm; midcavity, 26.3 ± 5.8 mm) were not associated with sex, age, or BMI except for the RV length (64.6 ± 8.9 mm), which was greater in male patients. Tricuspid annular plane systolic excursion (TAPSE) was 21.7 ± 2.8 mm, fractional area change was 42.1% ± 5.5%, tricuspid annular peak systolic velocity RV S' was 12.1 ± 1.9 m/sec, and RV free wall strain was -31.5% ± 8.6%. Age and BMI were not associated with right atrial (RA) volumetric measurements, RV linear measurements, or any RV functional parameters except TAPSE and RV A', which increased with BMI., Conclusions: This study establishes normal left and right heart parameters in a black African population. Aging was not associated with RA or RV parameters except for RV E' and A'. BMI does not affect RA/RV measurements but may cause variability in TAPSE and RV A'., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

The 34th annual Advances in Contrast Ultrasound (ACU) International Bubble Conference convened in Chicago, IL, USA, on September 5-6, 2019 to feature new directions of research, preclinical and first-in-man clinical trials, and novel clinical applications highlighting the diversity and utility of contrast enhanced ultrasound (CEUS). An expert group comprising clinicians, engineers, basic scientists, government officials, attorneys, and industry partners convened to collaborate on cutting-edge ultrasound enhancement technology. Utilizing this information, the International Contrast Ultrasound Society (ICUS) continues to have cause to advocate for the safe and appropriate use of CEUS with expanding indications and applications., (© 2020 The authors.)

Although hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy worldwide, the criteria for its definition and most of the literature concern the left ventricle, thus confirming the theory that the right ventricle is the neglected one. Right ventricular (RV) involvement includes structural and functional changes with significant impact on clinical presentation and prognosis. The pattern of RV hypertrophy can be variable with possible dynamic obstruction. Histological findings suggest similar pathogenetic changes in both ventricles supporting the common myopathic process with sarcomeric mutations. Systolic dysfunction of the RV is subtle, and the classical echocardiographic indices are usually within normal limits, while global longitudinal strain is significantly impaired. Diastolic dysfunction of the RV is also evident in patients with HCM possibly due to fibrosis of the RV free wall and/or the obstruction of the RV filling with significant prognostic implications. RV involvement in HCM is associated with increased incidence of supraventricular and ventricular arrhythmias, severe dyspnea, pulmonary thromboembolism, progressive heart failure, and increased risk of sudden cardiac death. Therefore, the RV should be routinely included in the detailed assessment of patients with HCM., (Copyright © 2018 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Stress echocardiography is an established technique for assessing coronary artery disease. It has primarily been used for the diagnosis and assessment of patients presenting with chest pain in whom there is an intermediate probability of coronary artery disease. In addition, it is used for risk stratification and to guide revascularisation in patients with known ischaemic heart disease. Although cardiac computed tomography has recently been recommended in the United Kingdom as the first-line investigation in patients presenting for the first time with atypical or typical angina, stress echocardiography continues to have an important role in the assessment of patients with lesions of uncertain functional significance and patients with known ischaemic heart disease who represent with chest pain. In this guideline from the British Society of Echocardiography, the indications and recommended protocols are outlined for the assessment of ischaemic heart disease by stress echocardiography.

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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

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 > 10 percentage units to a value < 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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Tricuspid regurgitation natural history and treatment remains poorly understood. Right ventricular function is a key factor in determining prognosis, timing for intervention and longer-term outcome. The right ventricle is a thin walled chamber with a predominance of longitudinal fibres and a shared ventricular septum. In health, the low-pressure pulmonary circulation results in a highly compliant RV well equipped to respond to changes in preload but sensitive to even small alterations in afterload. In Part 1 of this article, discussion focuses on key principles of ventricular function assessment and the importance of right ventricular chamber size, volumes and ejection fraction, particularly in risk stratification in tricuspid regurgitation. Part 2 of this article provides an understanding of the causes of tricuspid regurgitation in the contemporary era, with emphasis on key patient groups and their management.

Aims: Heart failure (HF) with mid-range ejection fraction (HFmrEF) shares similar diagnostic criteria to HF with preserved ejection fraction (HFpEF). Whether left atrial (LA) function differs between HFmrEF and HFpEF is unknown. We, therefore, used 2D-speckle-tracking echocardiography (2D-STE) to assess LA phasic function in patients with HFpEF and HFmrEF., Methods and Results: Consecutive outpatients diagnosed with HF according to current European recommendations were prospectively enrolled. There were 110 HFpEF and 61 HFmrEF patients with sinus rhythm, and 37 controls matched by age. LA phasic function was analysed using 2D-STE. Peak-atrial longitudinal strain (PALS), peak-atrial contraction strain (PACS), and PALS-PACS were measured reflecting LA reservoir, pump, and conduit function, respectively. Among HF groups, most of left ventricular (LV) diastolic function measures, and LA volume were similar. Both HF groups had abnormal LA phasic function compared with controls. HFmrEF patients had worse LA phasic function than HFpEF patients even among patients with LA enlargement. Among patients with normal LA size, LA reservoir, and pump function remained worse in HFmrEF. Differences in LA phasic function between HF groups remained significant after adjustment for confounders. Global PALS and PACS were inversely correlated with brain natriuretic peptide, LA volume, E/A, E/e', pulmonary artery systolic pressure, and diastolic dysfunction grade in both HF groups., Conclusion: LA phasic function was worse in HFmrEF patients compared with those with HFpEF regardless of LA size, and independent of potential confounders. These differences could be attributed to intrinsic LA myocardial dysfunction perhaps in relation to altered LV function., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: To review medical literature for evidence of association between hypertension and mitral regurgitation (MR) and summarize potential favorable effects of antihypertensive drugs on MR natural history and treatment., Recent Findings: Hypertension and MR are common diseases affecting a large proportion of the general population. Contemporary evidence suggests that hypertension may worsen the progression and prognosis of MR through augmented mechanical stress and increased regurgitation volume. Renin-angiotensin axis inhibitors, beta-blockers, and vasodilators have been tested in order to prevent or decrease primary or secondary MR. Although antihypertensive agents may improve hemodynamic parameters and left ventricular remodeling in primary MR, there is no strong evidence of benefit on clinical outcomes. On the other hand, a beneficial effect of these drugs on secondary MR is better established. Moreover, there are no studies evaluating a possible benefit of lower blood pressure targets in MR. Randomized controlled trials are warranted to elucidate the precise role of antihypertensive therapy on treatment of MR.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

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., (© 2018 The British Society of Echocardiography.)

Normal values provide the background for interpretation of quantitative imaging data and thus are essential information for daily routine. Nevertheless, the ways how normal values are obtained, presented and interpreted, often do not receive the attention they deserve. We review the concepts of normalcy, the implications of typical normal ranges including the types of distribution of normal data, the possibilities to index for confounding biological factors like body surface area and the limitations of the very concept of normal values, demonstrating that there are no easy statistical solutions for difficult clinical problems.

Cardiac arrhythmias refer to any abnormality or disturbance in the normal activation sequence of the myocardium and may be indicative of structural heart disease and the cause of significant cardiovascular complications and sudden cardiac death. The following review summarizes the current state-of-the-art knowledge on the role of echocardiography in the management of cardiac arrhythmias and focuses on atrial fibrillation and ventricular arrhythmias where echocardiography presents a particular diagnostic and prognostic interest. Moreover, a brief reference is made to the effect of cardiac arrhythmias and conduction abnormalities on echocardiographic examination., (Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Right ventricular function is the major determinant of morbidity and mortality in pulmonary arterial hypertension (PAH). The ESC risk assessment strategy for PAH is based on clinical status, exercise testing, NTproBNP, imaging and haemodynamics but does not include right ventricular function. Our aims were to test the power of resting echocardiographic measurements to classify PAH patients according to ESC exercise testing risk stratification cut-offs and to determine if the classification power of echocardiographic parameters varied in chronic thrombo-embolic pulmonary hypertension (CTEPH)., Methods: We prospectively and consecutively recruited 46 PAH patients and 42 CTEPH patients referred for cardio-pulmonary exercise testing and comprehensive transthoracic echocardiography. Exercise testing parameters analyzed were peak oxygen consumption, percentage of predicted maximal oxygen consumption and the slope of ventilation against carbon dioxide production. Receiver operator characteristic curves were used to determine the optimal diagnostic cut-off values of echocardiographic parameters for classifying the patients in intermediate or high risk category according to exercise testing., Results: Measurements of right ventricular systolic function were the best for classifying in PAH (area under the curve 0.815 to 0.935). Measurements of right ventricular pressure overload (0.810 to 0.909) were optimal for classifying according to exercise testing in CTEPH. Measurements of left ventricular function were of no use in either group., Conclusions: Measurements of right ventricular systolic function can classify according to exercise testing risk stratification cut-offs in PAH. However, this is not the case in CTEPH where pressure overload, rather than right ventricular function seems to be linked to exercise performance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: The association between fractional flow reserve (FFR) and dobutamine stress echocardiography (DSE) in real-world stable angina patients is scant and controversial whereas no such comparison exists with instantaneous wave-free ratio (iFR). The current retrospective study aimed to investigate the associations among these modalities in patients with stable coronary artery disease (CAD) and intermediate coronary lesions., Methods and Results: We studied 62 consecutive stable angina patients who underwent DSE and subsequently coronary angiography with FFR (in all 62) and iFR (in 46/62 patients) assessment of intermediate single-vessel lesions between 2014 and 2015. Using receiver operating characteristic (ROC) curves we sought to identify the optimal FFR and iFR cut-off points with the highest discriminative power to predict the DSE result. The kappa coefficient was used to assess the agreement between FFR, iFR and DSE. The mean age of the study cohort was 63.5±12 years and 35 (56.5%) were males. Thirteen (21%) lesions were adjudicated as causing reversible ischaemia on DSE. Using ROC (FFR predicting DSE result), the area under the curve was 0.952 (95% CI: 0.902 to 1), whereas for iFR it was 0.743 (95% CI: 0.560 to 0.927), pAUC comparison=0.03. The optimal FFR cut-off point predicting positive DSE was 0.80. There was strong agreement between DSE and FFR (kappa 0.682, p<0.001). There was only modest agreement between iFR and DSE (kappa 0.258, p=0.068) using a cut-off value of 0.9., Conclusions: In patients referred for evaluation of stable CAD, there was good agreement between DSE and FFR (87%) but less so with iFR (71.7%).

Aims: To assess whether resting right ventricular (RV) function assessed by Global RV longitudinal strain (RVLS) and RV fractional area change (FAC) is associated with exercise performance in pulmonary arterial hypertension (PAH) and in chronic thromboembolic pulmonary hypertension (CTEPH)., Methods and Results: We prospectively recruited 46 consecutive patients with PAH and 42 patients with CTEPH who were referred for cardio-pulmonary exercise testing (CPET) and transthoracic echocardiography. Resting RV systolic function was assessed with RVLS and FAC. CPET parameters analyzed were percentage of predicted maximal oxygen consumption (VO2max) and the slope of ventilation against carbon dioxide production (VE/VCO2). Spearman correlation was performed between echocardiographic measurements and CPET measurements. In PAH, spearman correlation found an association between RVLS and VE/VCO2 (coefficient = 0.556, P < 0.001) and percentage predicted VO2max (coefficient = -0.393, P = 0.007), while FAC was associated with VE/VCO2 (coefficient = -0.481, P = 0.001) and percentage of predicted VO2max (coefficient = 0.356, P = 0.015). Conversely, in CTEPH, resting RV function was neither associated with percentage of predicted VO2max nor with VE/VCO2, whether assessed by RVLS or FAC., Conclusion: In PAH, resting RV function as assessed by FAC or RVLS is associated with exercise performance and could therefore make a significant contribution to non-invasive assessment in PAH patients. This association is not found in CTEPH, suggesting a disconnection between resting RV function and exercise performance, with implications for the use of exercise measurements as a prognostic marker and clinical/research endpoint in CTEPH., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) is the first area of interventional cardiology where women are treated as often as men. In this analysis of the gender specific results of randomised controlled trials (RCTs) comparing TAVI with surgical aortic valve replacement (SAVR) we aimed to determine whether gender affects the survival comparison between TAVI and SAVR. We identified all RCTs comparing TAVI versus SAVR for severe AS and reporting 1 and/or 2year survival. Summary odds ratios (ORs) were obtained using a random-effects model. Heterogeneity was assessed using the Q statistic and I 2 . Four RCTs met the criteria, totalling 3758 patients, 1706 women and 2052 men. Amongst females, TAVI recipients had a significantly lower mortality than SAVR recipients, at 1year (OR 0.68; 95%CI 0.50 to 0.94) and at 2years (OR 0.74; 95%CI 0.58 to 0.95). Amongst males there was no difference in mortality between TAVI and SAVR, at 1year (OR 1.09; 95%CI 0.86 to 1.39) or 2years (OR 1.05; 95%CI 0.85 to 1.3). The difference in treatment effect between genders was significant at both 1year (p interaction =0.02) and 2years (p interaction =0.04). In women TAVI has a 26 to 31% lower mortality odds than SAVR. In men, there is no difference in mortality between TAVI and SAVR., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To investigate the effect of awareness of arterial hypertension on quality of life in hypertensive patients in Greece., Materials and Methods: This was a prospective observational study that included 189 aware hypertensive patients on treatment with antihypertensive therapy. Patients were ambulatory men or women ≥18 years old, with diagnosed essential hypertension. The administration and fulfillment of the questionnaires was given at the outpatient hypertensive clinic starting with the SF-36 and continuing with the BDI-I test., Results: The mean BDI score was 9.9 ± 6.9, and 58, 25, 8.9, and 7.3% were identified as without, with minimal, moderate, and 0.8% with severe depression, respectively. The mean score for physical component summary (PCS-36) was 48.9 ± 7.6, and the mean score for mental component summary (MCS-36) was 46.0 ± 10.6. The stage of hypertension was not an independent predictor for any of the SF-36 dimensions. Dippers had not different levels of health-related quality of life (HRQOL) as compared with non-dippers. LV hypertrophy was associated with lower scores on bodily pain ( p  < 0.05) and kidney failure was associated with lower scores on general health perception ( p  < 0.05). Female gender, increased age, and the presence of COPD were independently associated with lower physical and mental health scores ( p  < 0.05). Score on BDI independently correlated with all dimensions of SF-36, indicating that greater depression levels are associated with lower levels of HRQOL., Conclusion: The stage as well as awareness of arterial hypertension does not affect physical and mental health. The fact that arterial hypertension per se is not a symptomatic disease may explain these results at least in patients with uncomplicated hypertension.

Background: We sought to assess the long-term evolution of left ventricular (LV) function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy, in asymptomatic type 1 diabetic patients, over a 6-year follow-up., Design and Methods: Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular risk factors were compared to 26 matched healthy controls. Conventional, 2D and 3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year follow-up evaluation., Results: At baseline, diabetic patients had similar LV ejection fraction (60 vs 61%; P  = NS), but impaired longitudinal function, as assessed by 2D-global longitudinal strain (GLS) (-18.9 ± 2 vs -20.5 ± 2; P  = 0.0002) and 3D-GLS (-17.5 ± 2 vs -19 ± 2; P  = 0.003). At follow-up, diabetic patients had worsened longitudinal function compared to baseline (2D-GLS: -18.4 ± 1 vs -19.2 ± 1; P  = 0.03). Global circumferential (GCS) and radial (GRS) strains were unchanged at baseline and during follow-up. Metabolic status did not correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of a compensatory increase of circumferential and radial functions in advanced stages of the disease - long-term diabetes (GCS: -26 ± 3 vs -23.3 ± 3; P  = 0.008) and in the presence of microvascular complications (GRS: 38.8 ± 9 vs 34.3 ± 8; P  = 0.04)., Conclusions: Subclinical myocardial dysfunction can be detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by a mild decrease in longitudinal function at the follow-up, but did not extend to a clinical expression of the disease, as no death or over heart failure was reported., (© 2017 The authors.)