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Acute type A aortic dissection (ATAAD) is a life-threatening condition that requires emergency surgery to avert fatal outcome. Conventional surgical procedures comprise excision of the entry tear and replacement of the proximal aorta with a synthetic vascular graft. In patients with DeBakey type I dissection, this approach leaves a chronically dissected distal aorta, putting them at risk for progressive dilatation, dissection propagation and aortic rupture. Therefore, ATAAD survivors should undergo serial imaging for evaluation of the aortic valve, proximal and distal anastomoses, and the aortic segments beyond the distal anastomosis. The current narrative review aims to describe potential complications in the early and late phases after ATAAD surgery, with focus on their specific imaging findings.

AimsTo assess the level of transesophageal echocardiography (TOE) knowledge and skills of young cardiologists.Methods and resultsA European Association of Cardiovascular Imaging (EACVI) online study using the first fully virtual simulation-based software was conducted in two periods (9–12 December 2021 and 10–13 April 2022). All young cardiologists eligible to participate (ConclusionOnline evaluation of young cardiologists around the world showed a relatively low level of TOE skills and knowledge. Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and the EACVI certification for TOE were independently associated with a higher global score.

The diagnosis of heart failure (HF) primarily relies on signs and symptoms that are neither sensitive nor specific. This impedes timely diagnosis and delays effective therapies or interventions, despite the availability of several evidence-based treatments for HF. Through monumental collaborative efforts from representatives of HF societies worldwide, the universal definition of HF was published in 2021, to provide the necessary standardized framework required for clinical management, clinical trials, and research. This review elaborates the key concepts of the new universal definition of HF, highlighting the key merits and potential avenues, which can be nuanced further in future iterations. We also discuss the key implications of the universal definition document from the perspectives of various stakeholders within the healthcare framework, including patients, care providers, system/payers and policymakers.

The diagnosis of heart failure (HF) primarily relies on signs and symptoms that are neither sensitive nor specific. This impedes timely diagnosis and delays effective therapies or interventions, despite the availability of several evidence‐based treatments for HF. Through monumental collaborative efforts from representatives of HF societies worldwide, the universal definition of HF was published in 2021, to provide the necessary standardized framework required for clinical management, clinical trials, and research. This review elaborates the key concepts of the new universal definition of HF, highlighting the key merits and potential avenues, which can be nuanced further in future iterations. We also discuss the key implications of the universal definition document from the perspectives of various stakeholders within the healthcare framework, including patients, care providers, system/payers and policymakers.

Tricuspid regurgitation (TR) is a highly prevalent condition and an independent risk factor for adverse outcomes. Multiple clinical guidelines exist for the diagnosis and management of TR, but the recommendations may sometimes vary. We systematically reviewed high-quality guidelines with a specific focus on areas of agreement, disagreement and gaps in evidence. We searched MEDLINE and EMBASE (01/01/2011 - 30/08/2021), the Guidelines International Network International, Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, Google Scholar and websites of relevant organizations for contemporary guidelines that were rigorously developed (as assessed by the Appraisal of Guidelines for Research and Evaluation II tool). Three guidelines were finally retained. There was consensus on a TR grading system, recognition of isolated functional TR associated with atrial fibrillation, and indications for valve surgery in symptomatic vs asymptomatic patients, primary vs secondary, and isolated TR forms. Discrepancies exist on the role of biomarkers, complementary multi-modality imaging, exercise echocardiography and cardiopulmonary exercise testing for risk stratification and clinical decision-making of progressive TR and asymptomatic severe TR, management of atrial functional TR and choice of transcatheter tricuspid valve intervention (TTVI). Risk-based thresholds for quantitative TR grading, robust risk score models for TR surgery, surveillance intervals, population-based screening programmes, TTVI indications and consensus on endpoint definitions are lacking.

Acute type A aortic dissection (ATAAD) is a life-threatening condition that requires emergency surgery to avert fatal outcome. Conventional surgical procedures comprise excision of the entry tear and replacement of the proximal aorta with a synthetic vascular graft. In patients with DeBakey type I dissection, this approach leaves a chronically dissected distal aorta, putting them at risk for progressive dilatation, dissection propagation and aortic rupture. Therefore, ATAAD survivors should undergo serial imaging for evaluation of the aortic valve, proximal and distal anastomoses, and the aortic segments beyond the distal anastomosis. The current narrative review aims to describe potential complications in the early and late phases after ATAAD surgery, with focus on their specific imaging findings.

Assessment of right ventricular (RV) function is crucial for the evaluation of the dyspnoeic patient and/or with systemic venous congestion and provides powerful prognostic insights. It can be performed using different imaging modalities including standard and advanced echocardiographic techniques, cardiac magnetic resonance imaging, computed tomography, and radionuclide techniques, which should be used in a complementary fashion. Each modality has strengths and weaknesses based on which the choice of their use and in which combination may vary according to the different clinical scenarios as will be detailed in this review. The conclusions from multiple studies using different imaging techniques are concordant: RV function can be reliably assessed and is a critical predictor of clinical outcomes. ispartof: EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING vol:23 issue:7 pages:885-897 ispartof: location:England status: published

IntroductionIn patients with mitral annular disjunction (MAD), it can be difficult to assess the severity of mitral regurgitation (MR), as they present with a prolapsing volume (i.e. volume resulting from mitral valve prolapse, blood volume shift) rather than a regurgitant jet. The influence of the mitral prolapsing volume (MPV) on cardiac dimensions is unknown. We hypothesised that the severity of MR is underestimated in these patients. Our aim was to measure MPV and to investigate its influence on cardiac dimensions in patients with MAD.MethodsWe retrospectively included 131 consecutive patients with MAD from our institution’s echocardiographic database. Transthoracic echocardiography was used to assess MPV. Additionally, we established a control group of 617 consecutive patients with degenerative mitral valve disease and performed propensity score matching.ResultsMedian MPV in the MAD group was 12 ml. MPV was an independent predictor for left ventricular end-diastolic (LVEDD) and end-systolic diameter (LVESD) and left atrial volume (allp 15 ml), LVEDD (56 ± 6 mm vs 51 ± 6 mm,p p p = 0.04] were significantly increased compared to matched patients with degenerative mitral valve disease and similarly assessed severity of MR.ConclusionDue to a volume shift based on the MPV rather than an actual regurgitant jet, MR severity cannot be assessed adequately in MAD patients. Increased MPV induces ventricular and atrial enlargement. These findings warrant future studies to focus on MPV as an additional parameter for assessment of the severity of MR in MAD patients.

Objectives Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE. Study design: In this cross-sectional study, women with a history of normotensive HELLP (n=32), PE without HELLP (n=59), and PE with HELLP (n=101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. Main outcome measures: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and “double product” (to approximate energy consumption), indexed to LVM. Results LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals. Conclusions Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population.

AimAn echocardiographic algorithm derived by machine learning (e ' VM) characterizes pre-clinical individuals with different cardiac structure and function, biomarkers, and long-term risk of heart failure (HF). Our aim was the external validation of the e ' VM algorithm and to explore whether it may identify subgroups who benefit from spironolactone. Methods and resultsThe HOMAGE (Heart OMics in AGEing) trial enrolled participants at high risk of developing HF randomly assigned to spironolactone or placebo over 9 months. The e ' VM algorithm was applied to 416 participants (mean age 74 +/- 7 years, 25% women) with available echocardiographic variables (i.e. e ' mean, left ventricular end-diastolic volume and mass indexed by body surface area [LVMi]). The effects of spironolactone on changes in echocardiographic and biomarker variables were assessed across e ' VM phenotypes. A majority (>80%) had either a 'diastolic changes' (D), or 'diastolic changes with structural remodelling' (D/S) phenotype. The D/S phenotype had the highest LVMi, left atrial volume, E/e', natriuretic peptide and troponin levels (all p < 0.05). Spironolactone significantly reduced E/e' and B-type natriuretic peptide (BNP) levels in the D/S phenotype (p < 0.01), but not in other phenotypes (p > 0.10; p(interaction)

Valvular heart disease is a leading cause of cardiovascular morbidity and mortality and a major contributor of symptoms and functional disability. Knowledge of valvular heart disease epidemiology and a deep comprehension of the geographical and temporal trends are crucial for clinical advances and the formulation of effective health policy for primary and secondary prevention. This review mainly focuses on the epidemiology of primary (organic, related to the valve itself) valvular disease and its management, especially emphasizing the importance of heart valve centers in ensuring the best care of patients through a multidisciplinary team.

Background: Echocardiography is the diagnostic modality for assessing cardiac systolic and diastolic function to diagnose and manage heart failure. However, manual interpretation of echocardiograms can be time consuming and subject to human error. Therefore, we developed a fully automated deep learning workflow to classify, segment, and annotate two-dimensional (2D) videos and Doppler modalities in echocardiograms. Methods: We developed the workflow using a training dataset of 1145 echocardiograms and an internal test set of 406 echocardiograms from the prospective heart failure research platform (Asian Network for Translational Research and Cardiovascular Trials; ATTRaCT) in Asia, with previous manual tracings by expert sonographers. We validated the workflow against manual measurements in a curated dataset from Canada (Alberta Heart Failure Etiology and Analysis Research Team; HEART; n=1029 echocardiograms), a real-world dataset from Taiwan (n=31 241), the US-based EchoNet-Dynamic dataset (n=10 030), and in an independent prospective assessment of the Asian (ATTRaCT) and Canadian (Alberta HEART) datasets (n=142) with repeated independent measurements by two expert sonographers. Findings: In the ATTRaCT test set, the automated workflow classified 2D videos and Doppler modalities with accuracies (number of correct predictions divided by the total number of predictions) ranging from 0·91 to 0·99. Segmentations of the left ventricle and left atrium were accurate, with a mean Dice similarity coefficient greater than 93% for all. In the external datasets (n=1029 to 10 030 echocardiograms used as input), automated measurements showed good agreement with locally measured values, with a mean absolute error range of 9–25 mL for left ventricular volumes, 6–10% for left ventricular ejection fraction (LVEF), and 1·8–2·2 for the ratio of the mitral inflow E wave to the tissue Doppler e' wave (E/e' ratio); and reliably classified systolic dysfunction (LVEF

Aims Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. Methods and results In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4–76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3–2.9) m/s vs. lower tertiles 2.7 (2.4–3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05–1.41) vs. lower tertiles 1.17 (1.06–1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (−0.1–0.2) m/s/year vs. lower tertiles 0.1 (0.0–0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. Conclusion Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration.

Contains fulltext : 292501.pdf (Publisher’s version ) (Closed access) BACKGROUND: Supra-physiologic doses of anabolic androgenic steroids (AAS) lead to multiple cardiovascular complications. The long-term clinical effect of AAS overuse on cardiac structure and function, which persists during off-cycle periods, remains unclear. METHODS: A total of 15 sedentary subjects and 79 bodybuilders (26 AAS non-users and 53 AAS-users), matched for age and male gender, were assessed in a cross-sectional design for echocardiography measures. AAS-users were included during an off-cycle phase, abstained from AAS for at least 1 month. 2D standard M-mode and speckle tracking echocardiography were used to measure cardiac dimensions and functions. RESULTS: Inter-ventricular septum and posterior wall thickness were significantly higher among chronic off-cycle AAS-users compared to AAS non-users and sedentary group. Off-cycle AAS-users showed lower E/A ratio of the diastolic function. Left ventricular systolic function was not affected in terms of ejection fraction, but significant subclinical systolic dysfunction, assessed by GLS, was observed for chronic off-cycle AAS-users compared to AAS non-users (GLS = -16.8% vs. -18.5%, respectively; p = 0.001). Diameter of left atrium and right ventricle were significantly enlarged among off-cycle AAS-user bodybuilders (p = 0.002 and 0.040). TAPSE and RV S', and cardiac vasculature of aorta were comparable in all groups. CONCLUSIONS: This study demonstrates that during off-cycle phase, AAS-users show long-term impaired GLS, even after considerable AAS abstain, despite normal LVEF. It highlights the importance of following GLS to predict hypertrophy and heart failure events, and not relying on LVEF alone. In addition, the hypertrophic effect of chronic AAS consumption is transitional during AAS washout periods.

Background: This study aimed to define the normal ranges of echocardiographic parameters that are used to evaluate right ven-tricular systolic functions. Methods: A total of 607 children within the age range of 0-18 years without any cardiac pathology or chronic disorders were in-cluded in the study. The study population was categorized into different age groups and underwent transthoracic echocardiog-raphy. In this study, tricuspid annular plane systolic excursion (TAPSE), tricuspid annular peak systolic velocity (TAPSV), and right ventricular myocardial performance index (RVMPI) values were measured. Results: There was no statistically significant difference between the mean TAPSE and TAPSV values of male and female subjects. The mean RVMPI was higher in females than in males. The study population was categorized into nine groups according to their age. The TAPSE, TAPSV, and RVMPI values were calculated for each group. Additionally, the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, and +/- 2 standard deviation (SD) and +/- 3 SD values of TAPSE measurements were calculated for each age group. The study population was divided into eight groups according to their body surface area (BSA). Moreover, the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of TAPSE measurements were calculated. There was a strong positive correlation between TAPSE and BSA. The TAPSE was also positively correlated with TAPSV but not with RVMPI. Conclusions: This study determined the normal values for TAPSV and RVMPI. It is important to have knowledge of the normal ranges of these parameters to recognize right ventricular dysfunction early in various cardiac disorders.

ObjectivesTo evaluate the potential of soluble cluster of differentiation 146 (sCD146) in the detection and grading of congestion in patients with acute dyspnoea.DesignSubanalysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort.SettingTwo Lithuanian university centres.ParticipantsAdult patients with acute dyspnoea admitted to the emergency department.MethodsCongestion was assessed using clinical and sonographic parameters. All patients underwent sCD146 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing.ResultsThe median value of sCD146 concentration in the study cohort (n=437) was 405 (IQR 315–509) ng/mL. sCD146 was higher in patients with peripheral oedema than in those without (median (IQR) 472 (373–535) vs 400 (304–501) ng/mL, p=0.009) and with pulmonary rales than in those without (439 (335–528) vs 394 (296–484) ng/mL, p=0.001). We found a parallel increase of estimated right atrial pressure (eRAP) and sCD146 concentration: sCD146 was 337 (300–425), 404 (290–489) and 477 (363–572) ng/mL in patients with normal, moderately elevated and high eRAP, respectively (p=0.001). In patients with low NT-proBNP, high sCD146 distinguished a subgroup with a higher prevalence of oedema as compared with patients with low levels of both biomarkers (76.0% vs 41.0%, p=0.010). Moreover, high sCD146 indicated a higher prevalence of elevated eRAP, irrespective of NT-proBNP concentration (pConclusionsCD146 concentration reflects the degree of intravascular and tissue congestion assessed by clinical and echocardiographic indices, with this association maintained in patients with low NT-proBNP. Our data support the notion that NT-proBNP might represent heart stretch while sCD146 rather represents peripheral venous congestion.

AIMS: Non-invasive myocardial work (MW) is a validated index of left ventricular (LV) systolic performance, incorporating afterload and myocardial metabolism. The role of MW in predicting the first hospitalization for de novo heart failure with preserved ejection fraction (HFpEF) is still unknown. We aim to investigate the diagnostic performance of MW to predict the first de novo HFpEF hospitalization in ambulatory individuals with preserved LV ejection fraction. METHODS AND RESULTS: Twenty-nine patients with transthoracic echocardiography performed at least 6 months before the first HFpEF hospitalization were compared with 29 matched controls. MW was derived as the area of pressure-strain loop using speckle-tracking and brachial artery blood pressure. Global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE) were collected. First HFpEF hospitalization and its combination with cardiovascular death [major adverse cardiovascular events (MACE)] and all-cause of death [major adverse events (MAE)] were assessed. At baseline, future HFpEF patients showed lower global work index, global constructive work, GWE, and higher GWW than controls (all P 170 mmHg% was associated with a 4-fold increase of MACE (HR = 4.5, 95% CI 1.59-13.12, P = 0.005) and a 3-fold higher risk of MAE (HR = 2.9, 95% CI 1.24-6.6, P = 0.014). CONCLUSIONS: In ambulatory patients with preserved LV ejection fraction and risk factors, GWW showed high accuracy to predict the first HFpEF hospitalization and its combination with mortality. The GWW routine assessment may be clinically helpful in patients with dyspnoea. ispartof: ESC HEART FAILURE vol:9 issue:1 pages:373-384 ispartof: location:England status: published

While chronic thromboembolic pulmonary hypertension (CTEPH) results from macroscopic and microscopic obstruction of the pulmonary vascular bed, the function of the right ventricle (RV) and increased RV afterload are the main determinants of its symptoms and prognosis. In this review, we assess RV function in patients diagnosed with CTEPH with a focus on the contributions of RV afterload and dysfunction to the pathogenesis of this disease. We will also discuss changes in RV function and geometry in response to treatment, including medical therapy, pulmonary endarterectomy, and balloon pulmonary angioplasty. ispartof: JOURNAL OF CLINICAL MEDICINE vol:12 issue:1 ispartof: location:Switzerland status: published

Contains fulltext : 235000.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cardiotoxicity is a well-known side effect after anthracyclines and chest radiotherapy in childhood cancer survivors (CCS). The DCCSS LATER 2 CARD (cardiology) study includes evaluation of echocardiographic measurements for early identification of CCS at highest risk of developing heart failure. This paper describes the design, feasibility, and reproducibility of the echocardiography protocol. METHODS: Echocardiograms from CCS and sibling controls were prospectively obtained at the participating centers and centrally analyzed. We describe the image acquisition, measurement protocol, and software-specific considerations for myocardial strain analyses. We report the feasibility of the primary outcomes of systolic and diastolic function, as well as reproducibility analyses in 30 subjects. RESULTS: We obtained 1,679 echocardiograms. Biplane ejection fraction (LVEF) measurement was feasible in 91% and 96% of CCS and siblings, respectively, global longitudinal strain (GLS) in 80% and 91%, global circumferential strain (GCS) in 86% and 89%, and ≥2 diastolic function parameters in 99% and 100%, right ventricle free wall strain (RVFWS) in 57% and 65%, and left atrial reservoir strain (LASr) in 72% and 79%. Intra-class correlation coefficients for inter-observer variability were 0.85 for LVEF, 0.76 for GLS, 0.70 for GCS, 0.89 for RVFWS and 0.89 for LASr. Intra-class correlation coefficients for intra-observer variability were 0.87 for LVEF, 0.82 for GLS, 0.82 for GCS, 0.85 for RVFWS and 0.79 for LASr. CONCLUSION: The DCCSS LATER 2 CARD study includes a protocolized echocardiogram, with feasible and reproducible primary outcome measurements. This ensures high-quality outcome data for prevalence estimates and for reliable comparison of cardiac function parameters.

Congestion, related to pressure and/or fluid overload, plays a central role in the pathophysiology, presentation and prognosis of heart failure and is an important therapeutic target. While symptoms and physical signs of fluid overload are required to make a clinical diagnosis of heart failure, they lack both sensitivity and specificity, which might lead to diagnostic delay and uncertainty. Over the last decades, new ultrasound methods for the detection of elevated intracardiac pressures and/or fluid overload have been developed that are more sensitive and specific, thereby enabling earlier and more accurate diagnosis and facilitating treatment strategies. Accordingly, we considered that a state-of-the-art review of ultrasound methods for the detection and quantification of congestion was timely, including imaging of the heart, lungs (B-lines), kidneys (intrarenal venous flow), and venous system (inferior vena cava and internal jugular vein diameter).

OBJECTIVES This study aimed to explore echocardiographic characteristics of phospholamban (PLN) p.Arg14del mutation carriers to investigate whether structural and/or functional abnormalities could be identified before onset of symptoms.BACKGROUND Carriers of the genetic PLN p.Arg14del mutation may develop arrhythmogenic and/or dilated cardiomyopathy. Overt disease is preceded by a pre-symptomatic phase of variable length in which disease expression seems to be absent.METHODS PLN p.Arg14del mutation carriers with an available echocardiogram were included. Mutation carriers were classified as pre-symptomatic if they had no history of ventricular arrhythmias (VAs), a premature ventricular complex count of = 45%. In addition, we included 70 control subjects with similar age and sex distribution as the pre-symptomatic mutation carriers. Comprehensive echocardiographic analysis (including deformation imaging) was performed.RESULTS The final study population consisted of 281 PLN p.Arg14del mutation carriers, 139 of whom were classified as pre-symptomatic. In comparison to control subjects, pre-symptomatic mutation carriers had lower global longitudinal strain and higher LV mechanical dispersion (both p < 0.001). In addition, post-systolic shortening (PSS) in the LV apex was observed in 43 pre-symptomatic mutation carriers (31%) and in none of the control subjects. During a median follow-up of 3.2 years (interquartile range: 2.1 to 5.6 years) in 104 pre-symptomatic mutation carriers, nonsustained VA occurred in 13 (13%). Presence of apical PSS was the strongest echocardiographic predictor of VA (multivariable hazards ratio: 5.11; 95% confidence interval [CI]: 1.37 to 19.08; p = 0.015), which resulted in a negative predictive value of 96% (95% CI: 89% to 98%) and a positive predictive value of 29% (95% CI: 21% to 40%).CONCLUSIONS Global and regional LV mechanical alterations in PLN p.Arg14del mutation carriers precede arrhythmic symptoms and overt structural disease. Pre-symptomatic mutation carriers with normal deformation patterns in the apex are at low risk of developing VA within 3 years, whereas mutation carriers with apical PSS appear to be at higher risk. (C) 2021 by the American College of Cardiology Foundation.

The article is focused on actual experience of using specific digital instruments to communicate with civil society in part of providing sustainable national security. We aggregated the data about efficiency of using digital communication tools in actual reality of a full-scale war of Russia against Ukraine, and compare experience of the EU countries in digital communication in context of Ukraine`s European association. One of the most important fields of usage of specific digital communication tools to provide national security is the transparency and the public information access with supplying effective feedback. The usage of digital communication tools is gaining great importance in case of Ukraine, including and considering sustainable cyber, civil, economic, military and national security in realities of a full-scale war and safety threats. Finally, the other challenge is the need to utilize mobile applications for providing administrative services, which also rising considerable security concerns due to involvement of an extensive number of civil users. As a result of these processes, there is a need to transform and rethink the current usage of digital communication tools to provide proper balance between security and efficiency and economy of public services delivered via digital tools., Стаття присвячена актуальному досвіду використання конкретних цифрових інструментів комунікації з громадянським суспільством у частині забезпечення сталої національної безпеки. Ми агрегували дані про ефективність використання засобів цифрової комунікації в реальних умовах повномасштабної війни РФ проти України та порівняли досвід країн ЄС у цифровій комунікації в контексті євроасоціації України. Однією з найважливіших сфер використання специфічних засобів цифрової комунікації для забезпечення національної безпеки є прозорість та доступ до публічної інформації із забезпеченням ефективного зворотного зв’язку. Використання цифрових комунікаційних інструментів набуває великого значення у випадку України, включаючи та враховуючи сталу кібернетичну, цивільну, економічну, військову та національну безпеку в умовах повномасштабної війни та загроз безпеці. Нарешті, іншою проблемою є необхідність використання мобільних додатків для надання адміністративних послуг, що також викликає значні проблеми безпеки через залучення великої кількості цивільних користувачів. У результаті цих процесів виникає необхідність трансформувати та переосмислити поточне використання цифрових засобів зв’язку, щоб забезпечити належний баланс між безпекою, ефективністю та економічністю державних послуг, що надаються за допомогою цифрових інструментів.

Background Three-quarters of bladder cancer patients present with early-stage disease (non-muscle-invasive bladder cancer, NMIBC, UICC TNM stages Ta, T1 and Tis); however, most next-generation sequencing studies to date have concentrated on later-stage disease (muscle-invasive BC, stages T2+). We used exome and transcriptome sequencing to comprehensively characterise NMIBCs of all grades and stages to identify prognostic genes and pathways that could facilitate treatment decisions. Tumour grading is based upon microscopy and cellular appearances (grade 1 BCs are less aggressive, and grade 3 BCs are most aggressive), and we chose to also focus on the most clinically complex NMIBC subgroup, those patients with grade 3 pathological stage T1 (G3 pT1) disease. Methods Whole-exome and RNA sequencing were performed in total on 96 primary NMIBCs including 22 G1 pTa, 14 G3 pTa and 53 G3 pT1s, with both exome and RNA sequencing data generated from 75 of these individual samples. Associations between genomic alterations, expression profiles and progression-free survival (PFS) were investigated. Results NMIBCs clustered into 3 expression subtypes with different somatic alteration characteristics. Amplifications of ARNT and ERBB2 were significant indicators of worse PFS across all NMIBCs. High APOBEC mutagenesis and high tumour mutation burden were both potential indicators of better PFS in G3pT1 NMIBCs. The expression of individual genes was not prognostic in BCG-treated G3pT1 NMIBCs; however, downregulated interferon-alpha and gamma response pathways were significantly associated with worse PFS (adjusted p-value < 0.005). Conclusions Multi-omic data may facilitate better prognostication and selection of therapeutic interventions in patients with G3pT1 NMIBC. These findings demonstrate the potential for improving the management of high-risk NMIBC patients and warrant further prospective validation.

AIMS: Timely detection of subclinical left ventricular diastolic dysfunction (LVDDF) is of importance for precise risk stratification of asymptomatic subjects. Here, we evaluated the prevalence of LVDDF and its prognostic significance in the general population using two grading approaches: the 2016 ASE/EACVI recommendations and population-derived, age-specific criteria. METHODS AND RESULTS: We randomly recruited 1407 community-dwelling participants (mean age, 51.2 years; 51.1% women; 53.5% with cardiovascular risk factors). We measured left heart dimensions, strain, tricuspid regurgitation, transmitral blood flow, and mitral annular tissue velocities using conventional echocardiography and Doppler imaging. We utilized these measurements to grade of LVDDF according to the 2016 recommendations and population-derived, age-specific approach. According to the 2016 recommendations, 26 subjects (1.85%) were classified as having the advanced stage (Grade 2), whereas in 109 participants (7.75%) diastolic function was indeterminate. When applying the population-derived criteria, the prevalence of advanced LVDDF was 17.9% (n = 252). During the follow-up period (8.4 years), 100 participants experienced adverse cardiac events. After full adjustment, we did not observe any significant differences in the risk of events between subjects with indeterminate or any grade of LVDDF and subjects with normal diastolic function when classified according to the 2016 recommendation (P ≥ 0.25). In contrast, the adjusted risks of adverse cardiac events (HR = 1.28; P = 0.0045) were significantly elevated in participants with LVDDF when classified according to the population-derived criteria. CONCLUSIONS: Our study underscored the importance of considering age- and population-derived thresholds in LVDDF grading in subjects at high cardiovascular risk which led to a better risk stratification and outcome prediction. ispartof: ESC HEART FAILURE vol:9 issue:3 pages:1775-1783 ispartof: location:England status: published

Background: A systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm. Methods: In 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure. Results: Comorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e′ ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%–35%), E/e′ ratio (18%–29%), tricuspid regurgitation velocity (27%–41%), and tricuspid annular plane systolic excursion (13%) ( P Conclusions: Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.

Aims Recent studies showed that exercise-based cardiac rehabilitation (ECR) programmes are often not personalized to individual patient characteristics according to latest recommendations. This study investigates whether a computerized decision support (CDS) system based on latest recommendations and guidelines can improve personalization of ECR prescriptions. Pseudo-randomized intervention study. Methods and results Among participating Dutch cardiac rehabilitation centres, ECR programme characteristics of consecutive patients were recorded during 1 year. CDS was used during a randomly assigned 4-month period within this year. Primary outcome was concordance to latest recommendations in three phases (before, during, and after CDS) for 12 ECR programme characteristics. Secondary outcome was variation in training characteristics. We recruited ten Dutch CR centres and enrolled 2258 patients to the study. Overall concordance of ECR prescriptions was 59.9% in Phase 1, 62.1% in Phase 2 (P = 0.82), and 59.9% in Phase 3 (P = 0.56). Concordance varied from 0.0% to 99.9% for the 12 ECR characteristics. There was significant between-centre variation for most training characteristics in Phases 1 and 2. In Phase 3, there was only a significant variation for aerobic and resistance training intensity (P = 0.01), aerobic training volume (P Conclusion CDS did not substantially improve concordance with ECR prescriptions. As aerobic training volume was often lower than recommended and reduced during the study, a lack of institutional resources might be an important barrier in personalizing ECR prescriptions.

Contains fulltext : 229273.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Pregnancy complicated by preeclampsia and fetal growth restriction (FGR) relates to increased risk of cardiovascular disease later in life, but to different extents. Subclinical cardiac alterations precede eminent cardiovascular disease. Speckle-tracking echocardiography is an elegant method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to evaluate the prevalence of subclinical myocardial dysfunction in former preeclampsia patients (with and without FGR) compared with normotensive women with FGR. METHODS: For this cross-sectional study, we retrospectively selected women with a history of normotensive FGR (n = 17), preeclampsia with FGR (n = 26) and preeclampsia without FGR (n = 134) who underwent conventional echocardiography as part of the clinical cardiovascular work-up after complicated pregnancies between 6 months and 4 years postpartum in Maastricht, The Netherlands. We excluded women with chronic hypertension, hypercholesterolemia and obesity. RESULTS: Women with normotensive FGR showed subclinical left ventricular (LV) impairment in systodiastolic function with concentric remodeling, slight alteration in right ventricular systolic function and left atrial strain, similarly to the preeclampsia group independently from the fetal growth. LV hypertrophy was only present in about 10% of cases who experienced preeclampsia (independently from the fetal growth) but not in those with normotensive FGR. CONCLUSION: Similar to women with a history preeclampsia, women with a history of normotensive pregnancy but with FGR have abnormal myocardial function, shown with speckle-tracking echocardiography. Therefore, both preeclampsia and normotensive FGR should be viewed upon as risk indicator for subclinical myocardial impairment that may benefit from cardiovascular risk management.

Right ventricular (RV) function is important for clinical status and outcomes in children and adults with congenital heart disease (CHD). In the normal RV, longitudinal systolic function is the major contributor to global RV systolic function. A variety of factors contribute to RV failure including increased pressure- or volume-loading, electromechanical dyssynchrony, increased myocardial fibrosis, abnormal coronary perfusion, restricted filling capacity and adverse interactions between left ventricle (LV) and RV. We discuss the different imaging techniques both at rest and during exercise to define and detect RV failure. We identify the most important biomarkers for risk stratification in RV dysfunction, including abnormal NYHA class, decreased exercise capacity, low blood pressure, and increased levels of NTproBNP, troponin T, galectin-3 and growth differentiation factor 15. In adults with CHD (ACHD), fragmented QRS is independently associated with heart failure (HF) symptoms and impaired ventricular function. Furthermore, we discuss the different HF therapies in CHD but given the broad clinical spectrum of CHD, it is important to treat RV failure in a disease-specific manner and based on the specific alterations in hemodynamics. Here, we discuss how to detect and treat RV dysfunction in CHD in order to prevent or postpone RV failure. ispartof: CARDIOVASCULAR DIAGNOSIS AND THERAPY vol:10 issue:5 pages:1625-1645 ispartof: location:China status: published

The treatment aims for type 2 diabetes are to prevent complications and premature mortality, and improve quality of life. Glycaemic control is central to these aims; clinical guidelines have sought to achieve this with a stepwise approach starting with lifestyle measures and metformin, adding further medications once glycated haemoglobin (HbA1c) levels rise above a predefined threshold. However, treatment intensification can be delayed when HbA1c levels increase, and HbA1c levels become inadequately controlled in many patients. Clinical inertia can result in sustained elevated levels of HbA1c; when combined with a late diagnosis, this negatively impacts patients’ prognosis. Early combination therapy using medications with complementary modes of action could achieve optimal glycaemic targets and alter the course of the disease more than metformin alone. The multinational VERIFY study (clinicaltrials.gov NCT01528254) provided evidence accrued over 5 years, demonstrating the potential of early combination therapy: time to loss of glycaemic control was nearly doubled, and more than twice the number of patients experienced extended glycaemic control, with a vildagliptin–metformin combination therapy versus metformin alone. The study also showed a delay in secondary treatment failure in patients receiving the combination. Early combination therapy therefore offers a different trajectory to the stepwise approach. Translating these findings into clinical practice will require early detection and diagnosis of type 2 diabetes plus a shift in disease management. Nonetheless, the potential benefits of sustained and continuous disease control that early combination therapy offers represent the start of a new era in early diagnosis and intensive management, to achieve the treatment aims of type 2 diabetes., Plain Language Summary Blood glucose progressively increases over time in type 2 diabetes and is currently treated in a stepwise fashion, with more medications added when a single treatment fails. The VERIFY trial studied people with newly or recently diagnosed type 2 diabetes. Treating people early with two glucose-lowering drugs given together could slow the worsening of blood glucose levels, compared with starting with metformin first and then adding a second treatment later. Taking the two treatments together was as well tolerated as taking the single treatment alone. Starting treatment with two glucose-lowering drugs given together lengthened the time before insulin was needed, compared with starting with metformin and then adding a second treatment later. This is important to people with diabetes, as early treatment is straightforward but becomes increasingly complicated in later stages. The long-term benefits of this early combination treatment are awaited. In the meantime, the VERIFY trial has shown that combination therapy given at the start of treatment with medication can improve blood glucose levels and delay the need for insulin.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological As- sociation [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the re- sponses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identi- fied where no guidelines are available. Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male in- fertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical prac- tice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Purpose Results from large scale cardiovascular outcome trials in patients with type 2 diabetes mellitus (DM2) have found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular death and hospitalization for heart failure, but the mechanisms behind the beneficial cardiovascular effects are not fully understood. We tested the hypothesis that the SGLT2i, empagliflozin, improves non-endothelial dependent coronary microvascular function, thereby leading to better cardiac function. Methods Patients with DM2 followed at the endocrinology outpatient clinic at Bispebjerg University Hospital were included in a double blinded, placebo-controlled cross-over study. Participants were allocated equally to each treatment sequence using simple randomization and treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Echocardiographic parameters of cardiac function were measured, and blood samples were analyzed for a broad panel of cardiovascular biomarkers. Results Thirteen patients were randomized to each sequence and 10 and 9 completed the study according to protocol, respectively, and were included in the analysis of outcome parameters. We found no improvement in CFVR (change in the empagliflozin period was -0.16 (SD 0.58)). There were no effects on cardiac systolic function or indicators of cardiac filling pressure. Well-known effects of empagliflozin were obtained, such as weight loss and reduction in Hba1c level. Creatinine level increased but remained within normal range. We observed a clear trend of reduction in cardiovascular biomarkers after empagliflozin treatment and increased levels after the placebo period. No serious adverse reactions were reported. Conclusions Despite effect on weight-loss, Hba1c and biomarkers, treatment with empagliflozin for 12 weeks did not improve CFVR in patients with DM2.

Aim: The aim of this study is to compare the diameter of the inferior vena cava with tricuspid annular plane systolic excursion (TAPSE) measurement in order to determine the volume loss before and after blood donation in healthy volunteers. Methods: This Institutional Review Board-approved single center, prospective, cross-sectional study included 60 healthy blood donors donating in a tertiary care hospital's blood bank. After obtaining written consent, systolic, diastolic, and mean arterial blood pressures along with pulse rate of the donors were measured in sitting and supine positions by the attending physician, then, inferior vena cava (IVC) and TAPSE measurements were made before and after blood donation. Results: Statistically significant differences was found between standing systolic blood pressure and pulse rate, lying systolic blood pressure and pulse rate, IVC and TAPSE values before and after blood donation (p < 0.05). There was no difference between the other variables before and after blood donation. Conclusion: Our study revealed that, low IVC and TAPSE values correlated in determining blood loss after blood donation. TAPSE may be useful to predict blood loss in early stages of hypovolemic shock. (c) 2021 Published by Elsevier Inc.

Simple Summary The involvement of patients in decision making about their healthcare plans is being emphasized, but little is known how the decision making on palliative sedation is conducted and who are involved in. The aim of this study is to understand how decisions about palliative sedation are taken. The results may help to understand the reality of this decision-making considering when and by whom the decision-making process is initiated, patient involvement, family involvement and healthcare involvement. This may contribute to identifying aspects that should be improved. Abstract Background. The involvement of patients in decision making about their healthcare plans is being emphasized. In the context of palliative sedation, it is unclear how these decisions are made and who are involved in. The aim of the study is to understand how this decision-making is taken. Method. Information from a systematic review on clinical aspects of palliative sedation prospective studies were included. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014–December 2019). Data extraction and analysis regarded: (a) When and by whom the decision-making process is initiated; (b) patient involvement; (c) family involvement and (d) healthcare involvement. Results. Data about decision making were reported in 8/10 included articles. Palliative sedation was reported in 1137 patients (only 16 of them were non-cancer). Palliative sedation was introduced by the palliative care team during the disease process, at admission, or when patients experienced refractory symptoms. Only two studies explicitly mentioned the involvement of patients in decision making. Co-decision between families and the regular health care professionals was usual, and the health care professionals involved had been working in palliative care services. Conclusion. Patient participation in decision making appeared to be compromised by limited physical or cognitive capacity and family participation is described. The possibility of palliative sedation should be discussed earlier in the disease process.

Doppler echocardiography plays a central role in the assessment of pulmonary hypertension (PAH). We aim to improve quality assessment of systolic pulmonary arterial pressure (SPAP) by applying a cubic polynomial interpolation to digitized tricuspid regurgitation (TR) waveforms. Patients with PAH and advanced lung disease were divided into three cohorts: a derivation cohort (n = 44), a validation cohort (n = 71), an outlier cohort (n = 26), and a non-PAH cohort (n = 44). We digitized TR waveforms and analyzed normalized duration, skewness, kurtosis, and first and second derivatives of pressure. Cubic polynomial interpolation was applied to three physiology-driven phases: the isovolumic phase, ejection phase, and "shoulder" point phase. Coefficients of determination and a Bland-Altman analysis was used to assess bias between methods. The cubic polynomial interpolation of the TR waveform correlated strongly with expert read right ventricular systolic pressure (RVSP) with R 2 > 0.910 in the validation cohort. The biases when compared to invasive SPAP measured within 24 h were 6.03 [4.33; 7.73], -2.94 [1.47; 4.41], and -3.11 [-4.52; -1.71] mmHg, for isovolumic, ejection, and shoulder point interpolations, respectively. In the outlier cohort with more than 30% difference between echocardiographic estimates and invasive SPAP, cubic polynomial interpolation significantly reduced underestimation of RVSP. Cubic polynomial interpolation of the TR waveform based on isovolumic or early ejection phase may improve RVSP estimates. ispartof: PULMONARY CIRCULATION vol:12 issue:3 ispartof: location:United States status: published

Objective: Cardiac dysfunction has been reported in both cirrhotic and alcoholic patients. Our aim was to determine the relation of serum N-terminal pro-B-type natriuretic peptide (Nt-proBNP) levels to myocardial performance index (MPI) and disease severity in nonalcoholic cirrhotic patients. Patients and Methods: In this prospective study including 25 cirrhotic patients and 27 healthy controls, MPI was assessed by pulsed-wave tissue Doppler imaging (PW-TDI). The disease severity was determined by Child–Turcotte–Pugh (CTP ) and model for end-stage liver disease (MELD) scores. Results: There were no statistically significant differences in MPI levels between patients and controls (p< 0.246). Nt-proBNP levels (p< 0.0003), cardiac output (CO) (p< 0.0002), left ventricular end-systolic (LVES) volume (p< 0.031) and QT interval (p< 0.0001) increased. Left ventricular systolic function was normal in all cirrhotic patients when compared to controls. Nt-proBNP levels were positively correlated with MELD scores (p< 0.0001, r= 0.59), QT duration (p< 0.0001, r= 0.59), CO (p= 0,001, r= 0.44), right atrial (RA) area (p= 0.026, r= 0.31) and negatively correlated with diastolic BP (p= 0.015, r= -0.34). Conclusion: We conclude that in nonalcoholic cirrhotic patients, left ventricular MPI and systolic function were normal. Nt-proBNP levels were correlated with the disease severity and hyperdynamic circulation.

Background Dementia is widely considered a progressive condition associated with changes in cognitive capacities, which promotes the idea that people with dementia need to anticipate end-of-life care preferences. There is a growing body of interventions meant to support advance care planning (ACP) for people with dementia and their families. However, a deeper understanding of their experiences and expectations regarding planning the end of life is needed to inform ethically sound and person-centered ACP. This study explores how end-of-life care planning for people with dementia is experienced and perceived in practice. Methods We conducted a secondary analysis of qualitative data from in-depth interviews and ethnographic fieldwork. Participants included people with dementia living in the community or in nursing homes, family caregivers, and professional caregivers. During reflective sessions, the researchers moved back and forth between their original data and overarching topics related to ACP. Both performed deductive coding to filter relevant information from their data. Ongoing discussions allowed for the fine-tuning of themes. Results End-of-life care planning for people with dementia can encompass a paradox of control. While it may foster a sense of being in control, it may also feel like relinquishing control over future situations. It raises concerns regarding responsibility, as present, former and future wishes may not align. Family caregivers are often responsible for concrete end-of-life decision-making, prompting them to weigh previous wishes against present situations. Further, people with dementia may wish to focus on the present and distance themselves from the future. Discussion Advance decisions about end-of-life care are often decontextualized and people may find it difficult to oversee their future conditions and preferences. The widely recognized purpose of ACP to exert control over end-of-life care may need revision to match the needs of people with dementia while they are coping with their condition and an uncertain future.

Objective: The aim of the study was to describe the acute cardiotoxic effects of anthracycline chemotherapy in echocardiographic strain and electrocardiographic repolarization parameters in patients with breast cancer. Methods: A total of 35 consecutive patients (all females, mean age: 48.9 +/- 11.8 years) who received chemotherapy due to breast cancer were prospectively included. Pre-treatment (T0) and third month (T2) 2-dimensional strain echocardiography and electrocardiography were performed. Additionally, within 3 hours of the first dose of chemotherapy (T1), additional electrocardiographic images were obtained. All mechanical and electrical parameters from different time intervals (T0, T1, and T2) were compared with each other. Results: In the acute period after treatment, electrocardiographic repolarization parameters were prolonged and this prolongation continued to the third month (QT corrected with Bazett formula [440.10 +/- 27.63 (T0), 468.00 +/- 38.98 (T1), 467.86 +/- 35.09 (T2)], QT dispersion [49.85 +/- 19.52 (T0), 69.54 +/- 16.06 (T1), 57.63 +/- 14.42 (T2)], and T-wave peak-to-end interval [94.00 +/- 45.46 (T0), 131.20 +/- 17.79 (T1), 120.00 +/- 18.32 (T2)]; P

IntroductionCOVID-19 is associated with a marked systemic inflammatory response with concomitant cardiac injury and remodelling, but it is currently unknown whether the latter is reversible. Given that high-intensity interval training (HIIT) is a powerful stimulus to improve cardiorespiratory fitness while also eliciting marked anti-inflammatory effects, it may be an important countermeasure of reducing cardiopulmonary morbidity following COVID-19.Methods and analysis40 COVID-19 survivors who have been discharged from hospital will be included in this investigator-blinded randomised study with a 12-week HIIT intervention. Patients will be 1:1 block-randomised by sex to either a supervised HIIT exercise group or standard care (control group). The main hypothesis is that a 12-week HIIT scheme is a safe way to improve loss of cardiac mass and associated cardiorespiratory fitness, despite hypothesised limited HIIT-induced changes in conventional lung function indices per se. Ultimately, we hypothesise that the HIIT scheme will reduce post-COVID-19 symptoms and improve quality of life.Ethics and disseminationThis study is approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-20033733, including amendments 75068 and 75799) and registered at ClinicalTrials.gov (NCT04647734, pre-results). The findings will be published in a peer-reviewed journal, including cases of positive, negative and inconclusive results.Trial registration numberNCT04549337.

Background Vitamin K is associated with reduced cardiovascular disease risk such as heart failure, possibly by carboxylation of matrix-gla protein (MGP), a potent inhibitor of vascular calcification. The relationship of vitamin K intake or status with cardiac structure and function is largely unknown. Therefore this study aims to investigate the prospective association of vitamin K status and intake with echocardiographic measures. Methods This study included 427 participants from the Hoorn Study, a population-based cohort. Vitamin K status was assessed at baseline by plasma desphospho-uncarboxylated MGP (dp-ucMGP) with higher concentrations reflecting lower vitamin K status. Vitamin K intake was assessed at baseline with a validated food-frequency questionnaire. Echocardiography was performed at baseline and after a mean follow-up time of 7.6, SD=±0.7 years. We used linear regression for the association of vitamin K status and intake with left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI), adjusted for potential confounders. Results The mean age was 66.8, SD=±6.1 years (51% were male). A high vitamin K status was prospectively associated with decreased LVMI (change from baseline to follow-up: -5.0, 95% CI: -10.5;0.4 g/m2.7) for the highest quartile compared to the lowest in women (P-interaction sex=0.07). No association was found in men. Vitamin K status was not associated with LVEF or LAVI. Vitamin K intake was not associated with any of the echocardiographic measures. Conclusions This study showed a high vitamin K status being associated with decreased LVMI only in women, while intakes of vitamin K were not associated with any cardiac structure or function measures. These results extend previous findings for a role of vitamin K status to decrease heart failure risk.