<div><h4>Uptitrating Treatment After Heart Failure Hospitalization Across the Spectrum of Left Ventricular Ejection Fraction.</h4><i>Pagnesi M, Metra M, Cohen-Solal A, Edwards C, ... Mebazaa A, Davison B</i><br /><b>Background</b><br />Acute heart failure (AHF) is associated with a poor prognosis regardless of left ventricular ejection fraction (LVEF). STRONG-HF showed the efficacy and safety of a strategy of rapid uptitration of oral treatment for heart failure (HF) and close follow-up (high-intensity care), compared with usual care, in patients recently hospitalized for AHF and enrolled independently from their LVEF.<br /><b>Objectives</b><br />In this study, we sought to assess the impact of baseline LVEF on the effects of high-intensity care vs usual care in STRONG-HF.<br /><b>Methods</b><br />The STRONG-HF trial enrolled patients hospitalized for AHF with any LVEF and not treated with full doses of renin-angiotensin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. High-intensity care with uptitration of oral medications was performed independently from LVEF. The primary endpoint was the composite of HF rehospitalization or all-cause death at day 180.<br /><b>Results</b><br />Among the 1,078 patients randomized, 731 (68%) had LVEF ≤40% and 347 (32%) had LVEF >40%. The treatment benefit of high-intensity care vs usual care on the primary endpoint was consistent across the whole LVEF spectrum (interaction P with LVEF as a continuous variable = 0.372). Mean difference in the EQ-5D visual analog scale change from baseline to day 90 between treatment arms was slightly greater at higher LVEF values, but with no interaction between LVEF as a continuous variable and the treatment strategy (interaction P = 0.358). Serious adverse events were also independent from LVEF.<br /><b>Conclusions</b><br />Rapid uptitration of oral medications for HF and close follow-up reduce 180-day death and HF rehospitalization after AHF hospitalization independently from LVEF. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-ProBNP Testing, of Heart Failure Therapies [STRONG-HF]; NCT03412201).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 06 Jun 2023; 81:2131-2144</small></div>

<div><h4>Association of left ventricular strain-volume loop characteristics with adverse events in patients with heart failure with preserved ejection fraction.</h4><i>Kerstens TP, Weerts J, van Dijk APJ, Weijers G, ... van Empel VPM, Thijssen DHJ</i><br /><b>Aims</b><br />Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by impaired diastolic function. Left ventricular (LV) strain-volume loops (SVL) represent the relation between strain and volume during the cardiac cycle and provide insight into systolic and diastolic function characteristics. In this study, we examined the association of SVL parameters and adverse events in HFpEF.<br /><b>Methods and results</b><br />In 235 patients diagnosed with HFpEF, LV-SVL were constructed based on echocardiography images. The endpoint was a composite of all-cause mortality and Heart Failure (HF)-related hospitalization, which was extracted from electronic medical records. Cox-regression analysis was used to assess the association of SVL parameters and the composite endpoint, while adjusting for age, sex, and NYHA class. HFpEF patients (72.3% female) were 75.8 ± 6.9 years old, had a BMI of 29.9 ± 5.4 kg/m2, and a left ventricular ejection fraction of 60.3 ± 7.0%. Across 2.9 years (1.8-4.1) of follow-up, 73 Patients (31%) experienced an event. Early diastolic slope was significantly associated with adverse events [second quartile vs. first quartile: adjusted hazards ratio (HR) 0.42 (95%CI 0.20-0.88)] after adjusting for age, sex, and NYHA class. The association between LV peak strain and adverse events disappeared upon correction for potential confounders [adjusted HR 1.02 (95% CI 0.96-1.08)].<br /><b>Conclusion</b><br />Early diastolic slope, representing the relationship between changes in LV volume and strain during early diastole, but not other SVL-parameters, was associated with adverse events in patients with HFpEF during 2.9 years of follow-up.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Sodium-glucose cotransporter 2 inhibitors vs. sitagliptin in heart failure and type 2 diabetes: an observational cohort study.</h4><i>Fu EL, Patorno E, Everett BM, Vaduganathan M, ... Schneeweiss S, Desai RJ</i><br /><b>Aims</b><br />The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction.<br /><b>Methods and results</b><br />Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged ≥65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding.<br /><b>Conclusion</b><br />In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Effect of phosphodiesterase-5 inhibition on SystEmic Right VEntricular size and function - a multi-center, double-blind, randomized, placebo-controlled trial - SERVE.</h4><i>Greutmann M, Tobler D, Engel R, Heg D, ... Schwerzmann M, SERVE Investigators</i><br /><b>Background:</b><br/>and aims</b><br />In adults with congenital heart disease and systemic right ventricles, progressive right ventricular systolic dysfunction is common and is associated with adverse outcomes. Our aim was to assess the impact of the phosphodiesterase-5-inhibitor tadalafil on right ventricular systolic function.<br /><b>Methods and results</b><br />This was a double-blind, randomized, placebo-controlled, multi-center superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 years, SD 10.7), comparing tadalafil 20mg once daily versus placebo (1:1-ratio). Primary endpoint was the change in right ventricular endsystolic volume after three years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and NT-proBNP-concentration. Primary endpoint assessment by intention to treat analysis at three years of follow up was possible in 83 patients (42 patients in the tadalafil group and 41 patients in the placebo group). No significant changes over time in right ventricular endsystolic volumes were observed in the tadalafil and the placebo-group, and no significant differences between treatment groups (3.4ml, 95% CI, -4.3 to 11.0, p=0.39). No significant changes over time were observed for the pre-specified secondary endpoints for the entire study population, without differences between the tadalafil and the placebo-group.<br /><b>Conlcusions</b><br />In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro-hormonal activation remained stable over a three-year follow-up period. No significant treatment effect of tadalafil was observed. Further research is needed to find effective treatment for improvement of ventricular function in adults with systemic right ventricles. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Heart Failure Impairs Bone Marrow Hematopoietic Stem Cell Function and Responses to Injury.</h4><i>Marvasti TB, Alibhai FJ, Yang GJ, Li SH, ... Yau T, Li RK</i><br /><AbstractText><br /><b>Background:</b><br/>Heart failure (HF) is a clinical syndrome associated with a progressive decline in myocardial function and low-grade systemic inflammation. Chronic inflammation can have lasting effects on the bone marrow (BM) stem cell pool by impacting cell renewal and lineage differentiation. However, how HF affects BM stem/progenitor cells remains largely unexplored. Methods and Results EGFP<sup>+</sup> (Enchanced green fluorescent protein) mice were subjected to coronary artery ligation, and BM was collected 8 weeks after myocardial infarction. Transplantation of EGFP<sup>+</sup> BM into wild-type mice revealed reduced reconstitution potential of BM from mice subjected to myocardial infarction versus BM from sham mice. To study the effects HF has on human BM function, 71 patients, HF (n=20) and controls (n=51), who were scheduled for elective cardiac surgery were consented and enrolled in this study. Patients with HF exhibited more circulating blood myeloid cells, and analysis of patient BM revealed significant differences in cell composition and colony formation potential. Human CD34<sup>+</sup> cell reconstitution potential was also assessed using the NOD-SCID-IL2rγ<sup>null</sup> mouse xenotransplant model. NOD-SCID-IL2rγ<sup>null</sup> mice reconstituted with BM from patients with HF had significantly fewer engrafted human CD34<sup>+</sup> cells as well as reduced lymphoid cell production. Analysis of tissue repair responses using permanent left anteriordescending coronary artery ligation demonstrated reduced survival of HF-BM reconstituted mice as well as significant differences in human (donor) and mouse (host) cellular responses after MI. <br /><b>Conclusions:</b><br/>HF alters the BM composition, adversely affects cell reconstitution potential, and alters cellular responses to injury. Further studies are needed to determine whether restoring BM function can impact disease progression or improve cellular responses to injury.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e027727; epub ahead of print</small></div>

<div><h4>A narrative review of heart failure with preserved ejection fraction in breast cancer survivors.</h4><i>Yogeswaran V, Wadden E, Szewczyk W, Barac A, ... Cheng RK, Reding KW</i><br /><AbstractText>Advances in breast cancer (BC) treatment have contributed to improved survival, but BC survivors experience significant short-term and long-term cardiovascular mortality and morbidity, including an elevated risk of heart failure with preserved ejection fraction (HFpEF). Most research has focused on HF with reduced ejection fraction (HFrEF) after BC; however, recent studies suggest HFpEF is the more prevalent subtype after BC and is associated with substantial health burden. The increased HFpEF risk observed in BC survivors may be explained by treatment-related toxicity and by shared risk factors that heighten risk for both BC and HFpEF. Beyond risk factors with physiological impacts that drive HFpEF risk, such as hypertension and obesity, social determinants of health (SDOH) likely contribute to HFpEF risk after BC, impacting diagnosis, management and prognosis.Increasing clinical awareness of HFpEF after BC and screening for cardiovascular (CV) risk factors, in particular hypertension, may be beneficial in this high-risk population. When BC survivors develop HFpEF, treatment focuses on initiating guideline-directed medical therapy and addressing underlying comorbidities with pharmacotherapy or behavioural intervention. HFpEF in BC survivors is understudied. Future directions should focus on improving HFpEF prevention and treatment by building a deeper understanding of HFpEF aetiology and elucidating contributing risk factors and their pathogenesis in HFpEF in BC survivors, in particular the association with different BC treatment modalities, including radiation therapy, chemotherapy, biological therapy and endocrine therapy, for example, aromatase inhibitors. In addition, characterising how SDOH intersect with these therapies is of paramount importance to develop future prevention and management strategies.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 31 May 2023; epub ahead of print</small></div>

<div><h4>Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure in elderly patients: a sub-analysis of the STRONG-HF randomized clinical trial.</h4><i>Arrigo M, Biegus J, Asakage A, Mebazaa A, ... Cotter G, Cohen-Solal A</i><br /><b>Aims</b><br />STRONG-HF examined a high-intensity care (HIC) strategy of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up after acute heart failure (AHF) admission. We assess the role of age on efficacy and safety of HIC.<br /><b>Methods and results</b><br />Hospitalised AHF patients, not treated with optimal GDMT were randomized to HIC or usual care. The primary endpoint of 180-day death or HF-readmission occurred equally in older (>65 years, n=493, 74±5 years) and younger patients (53±11 years, adjusted hazard ratio [aHR] 1.02, 95% confidence interval [CI] 0.73-1.43, p=0.89). Older patients received slightly lower GDMT to day 21, but same doses at day 90 and 180. The effect of HIC on the primary endpoint was numerically higher in younger (aHR 0.51, 95% CI 0.32-0.82) than older patients (aHR 0.73, 95% CI 0.46-1.15, adjusted interaction-p=0.30), partially related to COVID-19 deaths. After exclusion of COVID-19 deaths, the effect of HIC was similar in younger (aHR 0.51, 95% CI 0.32-0.82) and older patients (aHR 0.63, 95% CI 0.32-1.02), adjusted interaction-p=0.56, with no treatment-by-age interaction (interaction-p=0.57). HIC induced larger improvements in quality of life to day 90 in younger (EQ-VAS adjusted-mean-difference 5.51, 95% CI 3.20-7.82) than in older patients (1.77, 95% CI -0.75-4.29, interaction-p=0.032). HIC was associated with similar rates of adverse events in older and younger patients.<br /><b>Conclusion</b><br />HIC after AHF was safe and resulted in a significant reduction of all-cause death or HF-readmission at 180 days across the study age spectrum. Older patients have smaller benefits in terms of quality of life. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 29 May 2023; epub ahead of print</small></div>

<div><h4>WATCH-DM risk score predicts the prognosis of diabetic phenotype patients with heart failure and preserved ejection fraction.</h4><i>Zhang X, Lv X, Wang N, Yu S, ... Cai M, Liu Y</i><br /><b>Background</b><br />Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Diabetes may identify an essential phenotype that significantly affects the prognosis of these patients. The WATCH-DM risk score has been validated for predicting the risk of heart failure in outpatients with type 2 diabetes mellitus (T2DM), but its ability to predict clinical outcomes in HFpEF patients with T2DM is unknown. We aimed to assess whether this risk score could predict the prognosis of diabetic phenotype patients with heart failure and preserved ejection fraction.<br /><b>Methods</b><br />We enrolled retrospectively 414 patients with HFpEF (70.03 ± 8.654 years, 58.70% female), including 203 (49.03%) type 2 diabetics. Diabetic HFpEF patients were stratified by baseline WATCH-DM risk score.<br /><b>Results</b><br />Diabetic HFpEF patients exhibited a trend toward more concentric remodeling/hypertrophy than nondiabetic HFpEF patients. When analyzed as a continuous variable, per 1-point increase in the WATCH-DM risk score was associated with increased risks of all-cause death (HR 1.181), cardiovascular death (HR 1.239), any hospitalization (HR 1.082), and HF hospitalization (HR 1.097). The AUC for the WATCH-DM risk score in predicting incident cardiovascular death (0.7061, 95% CI 0.6329-0.7792) was higher than that of all-cause death, any hospitalization, or HF hospitalization.<br /><b>Conclusions</b><br />As a high-risk phenotype for heart failure, diabetic HFpEF necessitates early risk stratification and specific treatment. To the best of our knowledge, the current study is the first to demonstrate that the WATCH-DM score predicts poor outcomes in diabetic HFpEF patients. Its convenience may allow for quick risk assessments in busy clinical settings.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 May 2023; epub ahead of print</small></div>

<div><h4>Lung Transplantation for Lung Cancer: a Systematic Review of the Literature.</h4><i>Elsolh B, Bayat Z, Lyu D, Lin J, Wakeam E</i><br /><b>Objective</b><br />Lung transplant (LTx) is an accepted treatment for end-stage pulmonary failure. A small proportion of explanted lungs harbor incidentally identified non-small cell lung cancers (NSCLC). We review the literature on studies assessing LTx patients found to have NSCLC lung cancer in their explanted lungs, and perform a pooled analysis of outcomes.<br /><b>Methods</b><br />MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. We included studies assessing outcomes of patients with incidentally identified NSCLC following LTx, or following LTx for diffuse lepidic adenocarcinoma as a primary indication.<br /><b>Results</b><br />A total of 1,404 articles were reviewed. 17 eligible studies were identified: 14 studies on incidental NSCLC (N=169), 4 on diffuse lepidic adenocarcinoma (N=70). Overall survival for patients with incidentally identified lung cancer at 1-year, 3-years, and 5-years was 60.8% (95%CI 43.7 - 77.9%, I<sup>2</sup> = 81.8%), 25.5% (95%CI 1.6 - 49.5%, I<sup>2</sup> = 93.6%), and 23.0% (95%CI 2.0 - 44.0%, I<sup>2</sup> = 92.0%) respectively. When restricted to those with earlier stage disease, those with stage I or II NSCLC had better 1-year, 3-year, and 5-year OS at 72.7% (95%CI 57.2 - 88.2%, I<sup>2</sup> = 67.3%), 41.6% (95%CI 14.0 - 69.1%, I<sup>2</sup> = 89.1%), and 34.5% (95%CI 8.1 - 61.0%, I<sup>2</sup> = 89.8%) respectively. A sensitivity analysis limited to stage I showed 1-year, 3-year, and 5-year survival of 73.0% (95%CI 56.3 - 89.7%), 40.4% (95%CI 110.3 - 70.6%), and 35.4% (95%CI 6.2 - 64.5%) respectively. The 4 studies on diffuse lepidic adenocarcinoma were too heterogeneous for pooled analysis.<br /><b>Conclusions</b><br />We present a review and pooled analysis examining survival following LTx with incidentally identified NSCLC. Patients with earlier stage incidentally explanted NSCLC had better survival outcomes. Overall survival in the Stage I population approximates that of LTx without incidental NSCLC.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 28 May 2023; epub ahead of print</small></div>

<div><h4>Sex-Associated Differences in the Clinical Outcomes of Left Ventricular Assist Device Recipients: Insights From Interagency Registry for Mechanically Assisted Circulatory Support.</h4><i>Shetty NS, Parcha V, Abdelmessih P, Patel N, ... Arora G, Arora P</i><br /><b>Background</b><br />Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking.<br /><b>Methods</b><br />Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21-30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups.<br /><b>Results</b><br />Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HR<sub>adj</sub>], 1.75 [1.23-2.47]) females had the highest risk of death followed by non-Hispanic White females (HR<sub>adj</sub>, 1.15 [1.07-1.25]; <i>P</i><sub>interaction</sub>=0.02). Hispanic (HR<sub>adj</sub>, 0.60 [0.40-0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HR<sub>adj</sub>, 0.76 [0.67-0.86]), and non-Hispanic White females (HR<sub>adj</sub>, 0.88 [0.80-0.96]) compared with their male counterparts (<i>P</i><sub>interaction</sub><0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HR<sub>adj</sub>, 1.32 [1.18-1.48]) had the highest risk of death (<i>P</i><sub>interaction</sub>=0.01). The risk of death (<i>P</i><sub>interaction</sub>=0.44) and cumulative incidence of heart transplantation (<i>P</i><sub>interaction</sub>=0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups.<br /><b>Conclusions</b><br />Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups.<br /><br /><br /><br /><small>Circ Heart Fail: 26 May 2023:e010189; epub ahead of print</small></div>

<div><h4>Sex-Specific Outcomes of Candidates Listed as the Highest Priority Status for Heart Transplantation.</h4><i>DeFilippis EM, Masotti M, Blumer V, Maharaj V, Cogswell R</i><br /><b>Background</b><br />While sex differences in heart transplantation (HT) waitlist mortality have been previously described, waitlist and HT outcomes by sex of patients in the highest urgency strata (Status 1) since implementation of the 2018 allocation system change in the United States are unknown. We hypothesized that women listed as Status 1 may have worse outcomes due to adverse events on temporary mechanical circulatory support.<br /><b>Methods</b><br />The analysis included adult, single-organ HT waitlist candidates listed as Status 1 at any time while listed, after the HT allocation system change (from October 18, 2018 through March 31, 2022). The primary outcome was the rate of HT by sex, assessed using multivariable competing risk analysis where waitlist removal for death or clinical deterioration was the competing event. Post-HT survival by sex of waitlist candidates transplanted as a Status 1 was also compared.<br /><b>Results</b><br />Of 1120 Status 1 waitlist candidates (23.8% women), women had a lower rate of HT compared to men (adjusted hazard ratio, 0.74 [95% CI, 0.62-0.88]; <i>P</i><0.001) and a higher rate of delisting for death or medical unsuitability (adjusted hazard ratio, 1.48 [95% CI, 1.05-2.09]; <i>P</i>=0.026). Calculated panel reactive antibody did not account for all the harm observed. Post-HT survival of Status 1 candidates by sex was similar (adjusted hazard ratio, 1.13 [95% CI, 0.62-2.06]; <i>P</i>=0.70).<br /><b>Conclusions</b><br />Women have a lower rate of HT and higher rate of delisting for death or clinical deterioration at the highest urgent status, which appears to be mediated but not fully explained by calculated panel reactive antibody levels. Further investigation into the safety profile of temporary mechanical circulatory support devices in women is needed.<br /><br /><br /><br /><small>Circ Heart Fail: 26 May 2023:e009946; epub ahead of print</small></div>

<div><h4>Prognostic Value of 6-Minute Walk Test in Advanced Heart Failure With Reduced Ejection Fraction.</h4><i>Scrutinio D, Guida P, Passantino A</i><br /><AbstractText>There is limited evidence regarding the prognostic value of the 6-minute walk test for patients with advanced heart failure (HF). Accordingly, we studied 260 patients presenting to inpatient cardiac rehabilitation (CR) with advanced HF. The primary outcome was 3-year all-cause mortality after discharge from CR. The association between 6-minute walk distance (6MWD) and the primary outcome was determined using the multivariable Cox regression analysis. To avoid collinearity, 6MWD at admission (6MWD<sub>adm</sub>) to CR and 6MWD at discharge (6MWD<sub>disch</sub>) from CR were analyzed separately. At multivariable analysis, 4 baseline characteristics (age, ejection fraction, systolic blood pressure, and blood urea nitrogen) were identified as prognostic of the primary outcome (baseline risk model). After adjusting for the baseline risk model, the hazard ratios of 6MWD<sub>adm</sub> and 6MWD<sub>disch</sub> modeled as per 50-m increase for the primary outcome were 0.92 (95% confidence interval [CI] 0.85 to 0.99, p = 0.035) and 0.93 (95% CI 0.88 to 0.99, p = -017), respectively. After adjusting for the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score, the corresponding hazard ratios were 0.91 (95% CI 0.84 to 0.98, p = 0.017) and 0.93 (95% CI 0.88 to 0.99, p = 0.016). The addition of either 6MWD<sub>adm</sub> or 6MWD<sub>disch</sub> to the baseline risk model or the MAGGIC score yielded a statistically significant increase in global chi-square and in the net proportion of survivors reclassified downward. In conclusion, our data suggest that the distance covered during a 6-minute walk test predicts survival and provides incremental prognostic information on the top of well-established prognostic factors and the MAGGIC risk score in advanced HF.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 26 May 2023; 199:37-43</small></div>

<div><h4>Dynamics of bacterial pathogens at the driveline exit site in patients with ventricular assist devices: a prospective, observational, single-centre cohort study.</h4><i>Pitton M, Valente LG, Oberhaensli S, Casanova C, ... Que YA, Fürholz M</i><br /><b>Background</b><br />Driveline infections (DLIs) at the exit site are frequent in patients with left ventricular assist devices (LVADs). The dynamics from colonization to infection are yet to be investigated. We combined systematic swabbing at the driveline exit site and genomic analyses to study the dynamics of bacterial pathogens and get insights into DLIs pathogenesis.<br /><b>Methods</b><br />A prospective, observational, single-centre cohort study at the University Hospital of Bern, Switzerland was performed. Patients with LVAD were systematically swabbed at the driveline exit site between June 2019 and December 2021, irrespective of signs and symptoms of DLI. Bacterial isolates were identified and a subset was whole-genome sequenced.<br /><b>Results</b><br />Fifty-three patients were screened, of which 45 (84.9%) were included in the final population. Bacterial colonization at the driveline exit site without manifestation of DLI was frequent and observed in 17 patients (37.8%). Twenty-two patients (48.9%) developed at least one DLI episode over the study period. Incidence of DLIs reached 2.3 cases per 1,000 LVAD days. The majority of the organisms cultivated from exit sites were Staphylococcus species. Genome analysis revealed that bacteria persisted at the driveline exit site over time. In four patients, transition from colonization to clinical DLI was observed.<br /><b>Conclusion</b><br />Our study is the first to address bacterial colonization in the LVAD-DLI setting. We observed that bacterial colonization at the driveline exit site was a frequent phenomenon, and in a few cases it preceded clinically relevant infections. We also provided acquisition of hospital-acquired multidrug-resistant bacteria and the transmission of pathogens between patients.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 26 May 2023; epub ahead of print</small></div>

<div><h4>Comparison of 30-day Readmission Rates and Inpatient Cardiac Procedures for Weekday versus Weekend Hospital Admissions for Heart Failure.</h4><i>Aliyev N, Almani MU, Qudrat-Ullah M, Butler J, Khan MS, Greene SJ</i><br /><b>Background</b><br />Whether timing of hospital presentation impacts care delivery and clinical outcomes for patients hospitalized for heart failure (HF) remains a matter of debate. In this study, we examined all-cause and HF-specific 30-day readmission rates for patients who were admitted for HF on a weekend versus admitted for HF on a weekday.<br /><b>Methods</b><br />We conducted a retrospective analysis using the 2010 - 2019 Nationwide Readmission Database to compare 30-day readmission rates among patients who were admitted for HF on a weekday (Monday-Friday) versus patients who were admitted for HF on a weekend (Saturday-Sunday). We also compared in-hospital cardiac procedures and temporal trends in 30-day readmission by day of index hospital admission.<br /><b>Results</b><br />Among 8,270,717 index HF hospitalizations, 6,302,775 were admitted on weekday and 1,967,942 admitted on a weekend. For weekday and weekend admissions, the 30-day all-cause readmission rates were 19.8% versus 20.3%, and HF-specific readmission rates were 8.1% versus 8.4%, respectively. Weekend admissions were independently associated with higher risk of all-cause (aOR 1.04, 95% CI 1.03 - 1.05, p<0.001) and HF-specific readmission (aOR 1.04, 95% CI 1.03 - 1.05, p<0.001). Weekend HF admissions were less likely to undergo echocardiography (aOR 0.95, 95% CI 0.94 - 0.96, p<0.001), right heart catheterization (aOR 0.80, 95% CI 0.79 - 0.81, p<0.001), electrical cardioversion (aOR 0.90, 95% CI 0.88 - 0.93, p<0.001) and temporary mechanical support devices (aOR 0.84, 95% CI 0.79 - 0.89, p<0.001). Mean length of stay was shorter for weekend HF admissions (5.1 versus 5.4 days, p<0.001). Between 2010 and 2019, 30-day all-cause (18.5% to 18.2%, trend p<0.001) and HF-specific (8.4% to 8.3%, trend p <0.001) readmission rates decreased among weekday HF admissions. Among weekend HF admissions, the HF-specific 30-day readmission rate decreased (8.8% to 8.7%, trend p<0.001), but all-cause 30-day readmission rate remained stable (trend p=0.280).<br /><b>Conclusions</b><br />Among patients hospitalized for HF, weekend admissions were independently associated with excess risk of 30-day all-cause and HF-specific readmission and lower likelihood of undergoing in-hospital cardiovascular testing and procedures. The 30-day all-cause readmission rate has decreased modestly over time among patients admitted on weekdays, but has remained stable among patients admitted on weekends.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 25 May 2023; epub ahead of print</small></div>

<div><h4>Contribution of skin cancer to overall healthcare costs of lung transplantation in Queensland, Australia.</h4><i>Gordon LG, Hopkins P, Chambers D, Green AC</i><br /><b>Background</b><br />Skin cancers are a major source of morbidity in lung transplant recipients but relative costs associated with their treatment are unknown.<br /><b>Methods</b><br />We prospectively followed 90 lung transplant recipients from enrolment in the Skin Tumours in Allograft Recipients study in 2013 to 2015, until mid-2016. We undertook a cost-analysis to quantify the health system costs relating to the index transplant episode, and ongoing costs for four years. Linked data from surveys, Australian Medicare claims and hospital accounting systems were used and generalized linear models were employed.<br /><b>Results</b><br />Median initial hospitalisation costs of lung transplantation were AU$115,831 (interquartile range (IQR) $87,428 - $177,395). In total, 57/90 (63%) participants were treated for skin cancers during follow-up at a total cost of AU$44,038. Among these 57, total government costs per person (mostly of pharmaceuticals) over four years, were median AU$68,489 (IQR $44,682 - $113,055) vs AU$59,088 (IQR $38,190 - $94,906) among those without skin cancer, with the difference predominantly driven by more doctors\' visits, and higher pathology and procedural costs. Healthcare costs overall were also significantly higher in those treated for skin cancers (cost ratio 1.50, 95%CI: 1.09, 2.06) after adjusting for underlying lung disease, age on enrolment, years of immunosuppression and number of treated comorbidities.<br /><b>Conclusion</b><br />Skin cancer care is a small component of overall costs. While all lung transplant recipients with comorbidities have substantial healthcare costs, those affected by skin cancer incur even greater healthcare costs than those without, highlighting the importance of skin cancer control.<br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 25 May 2023; epub ahead of print</small></div>

<div><h4>Safety and Efficacy of Empagliflozin and Diuretic Use in Patients with Heart Failure and Preserved Ejection Fraction: A Post Hoc Analysis of the EMPEROR-Preserved Trial.</h4><i>Butler J, Usman MS, Filippatos G, Ferreira JP, ... Packer M, Anker S</i><br /><b>Importance</b><br />The diuretic effect of sodium-glucose cotransporter 2 inhibitors may result in interaction with background diuretic therapy in patients with heart failure and preserved ejection fraction (HFpEF).<br /><b>Objective</b><br />To assess the safety and efficacy of empagliflozin in combination with background diuretic therapy and the association of empagliflozin with the need for conventional diuretics.<br /><b>Design, setting, and participants</b><br />This was a post hoc analysis of the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved). EMPEROR-Preserved was a phase 3, randomized, placebo-controlled, double-blind clinical trial conducted from March 2017 to April 2021. Patients with class II to IV heart failure and left ventricular ejection fraction greater than 40% were included. Of 5988 patients enrolled, 5815 (97.1%) had baseline data on diuretic use and were included in this analysis, which was conducted from November 2021 to August 2022.<br /><b>Interventions</b><br />Participants in EMPEROR-Preserved were randomized to empagliflozin or placebo. In this analysis, participants were divided into 4 subgroups: no diuretics and furosemide-equivalent diuretic dose of less than 40 mg, 40 mg, and greater than 40 mg at baseline.<br /><b>Main outcomes and measures</b><br />The main outcomes of interest were first hospitalization for heart failure (HHF) or cardiovascular death (CV death) and its components. Association of empagliflozin vs placebo with outcomes by baseline diuretic status (no diuretic vs any dose) and dose (no diuretic, <40 mg, 40 mg, and > 40mg) was assessed. Association of empagliflozin use with changes in diuretic therapy was also studied.<br /><b>Results</b><br />Among 5815 patients (mean [SD] age, 71.9 [9.4] years; 2594 [44.6%] female) with known baseline diuretic use, 1179 (20.3%) were not taking diuretics, 1725 (29.7%) were taking less than 40 mg, 1772 (30.5%) were taking 40 mg, and 1139 (19.6%) were taking greater than 40 mg. In the placebo arm, patients with higher diuretic doses had worse outcomes. Empagliflozin decreased the risk of HHF or CV death, regardless of background diuretic status (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93] for the diuretic group vs HR, 0.72; 95% CI, 0.48-1.06 for the nondiuretic group; P for interaction = .58). Similarly, diuretic status was not associated with changes in improvements in first HHF, total HHF, rate of decline in estimated glomerular filtration rate, and Kansas City Cardiomyopathy Questionnaire 23 clinical summary score with empagliflozin. Findings were consistent when patients were categorized by diuretic dose. Empagliflozin was associated with a decreased likelihood of diuretic dose escalation (HR, 0.74; 95% CI, 0.65-0.84) and an increased likelihood of de-escalation (HR, 1.15; 95% CI, 1.02-1.30). Empagliflozin was associated with an increased risk of volume depletion in patients taking diuretics (HR, 1.34; 95% CI, 1.13-1.59).<br /><b>Conclusion</b><br />In this study, treatment with empagliflozin was similar regardless of diuretic use or dose. Empagliflozin use was associated with decreased conventional diuretic dosing.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03057951.<br /><br /><br /><br /><small>JAMA Cardiol: 24 May 2023; epub ahead of print</small></div>

<div><h4>Sodium-glucose cotransporter 2 inhibitor may not prevent atrial fibrillation in patients with heart failure: a systematic review.</h4><i>Ouyang X, Wang J, Chen Q, Peng L, Li S, Tang X</i><br /><b>Background</b><br />Atrial fibrillation (AF) and heart failure (HF) frequently coexist because of their similar pathological basis. However, whether sodium-glucose cotransporter 2 inhibitor (SGLT2i), a novel class of anti-HF medication, decreases the risk of AF in HF patients remains unclear.<br /><b>Objectives</b><br />The aim of this study was to assess the relationship between SGLT2i and AF in HF patients.<br /><b>Methods</b><br />A meta-analysis of randomized controlled trails evaluating the effects of SGLT2i on AF in HF patients was performed. PubMed and ClinicalTrails.gov were searched for eligible studies until 27 November 2022. The risk of bias and quality of evidence were assessed through the Cochrane tool. Pooled risk ratio of AF for SGLT2i versus placebo in eligible studies was calculated.<br /><b>Results</b><br />A total of 10 eligible RCTs examining 16,579 patients were included in the analysis. AF events occurred in 4.20% (348/8292) patients treated with SGLT2i, and in 4.57% (379/8287) patients treated with placebo. Meta-analysis showed that SGLT2i did not significantly reduce the risk of AF (RR 0.92; 95% CI 0.80-1.06; p = 0.23) in HF patients when compared to placebo. Similar results remained in the subgroup analyses, regardless of the type of SGLT2i, the type of HF, and the duration of follow-up.<br /><b>Conclusions</b><br />Current evidences showed that SGLT2i may have no preventive effects on the risk of AF in patients with HF.<br /><b>Translational perspective</b><br />Despite HF being one of the most common heart diseases and conferring increased risk for AF, affective prevention of AF in HF patients is still unresolved. The present meta-analysis demonstrated that SGLT2i may have no preventive effects on reducing AF in patients with HF. How to effectively prevent and early detect the occurrence of AF is worth discussing.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 May 2023; 22:124</small></div>

<div><h4>Heart failure and obesity: The latest pandemic.</h4><i>Aryee E, Ozkan B, Ndumele CE</i><br /><AbstractText>The marked rise in rates of obesity, which is most prominent among individuals from socio-economically disadvantaged circumstances, has been a powerful contributor to the rising prevalence of heart failure (HF). Obesity has indirect effects on HF through the development of several metabolic risk factors, but also direct adverse effects on the myocardium. Obesity contributes to myocardial dysfunction and HF risk through multiple mechanisms, including hemodynamic changes, neurohormonal activation, endocrine and paracrine effects of adipose tissue, ectopic fat deposition and lipotoxicity. These processes principally result in concentric left ventricular (LV) remodeling and predominant increase in the risk for HF with preserved LV ejection fraction (HFpEF). Despite the excess risk for HF associated with obesity, there is a well described obesity paradox in which individuals with overweight and grade I obesity have better survival than those with normal weight and overweight. Despite the obesity paradox among individuals with prevalent HF, intentional weight loss is associated with improvements in metabolic risk factors, myocardial dysfunction and quality of life, in a dose-response fashion. In matched observational studies of bariatric surgery patients, marked weight loss is associated with decreased risk for developing HF, as well as improved cardiovascular disease (CVD) outcomes in those with existing HF. Ongoing clinical trials using powerful new obesity pharmacotherapies in individuals in with obesity and CVD may provide definitive information regarding the cardiovascular impact of weight loss. Given the powerful contribution of rising obesity prevalence to rates of HF, addressing these intertwined epidemics is a clinical and public health priority.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Prog Cardiovasc Dis: 24 May 2023; epub ahead of print</small></div>

<div><h4>Natriuretic Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload.</h4><i>Verbrugge FH, Martens P, Dauw J, Nijst P, ... Dupont M, Mullens W</i><br /><b>Background</b><br />Acetazolamide facilitates decongestion in acute decompensated heart failure (ADHF).<br /><b>Objectives</b><br />This study sought to investigate the effect of acetazolamide on natriuresis in ADHF and its relationship with outcomes.<br /><b>Methods</b><br />Patients from the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial with complete data on urine output and urine sodium concentration (UNa) were analyzed. Predictors of natriuresis and its relationship with the main trial endpoints were evaluated.<br /><b>Results</b><br />This analysis included 462 of 519 patients (89%) from the ADVOR trial. During 2 days after randomization, UNa was 92 ± 25 mmol/L on average, and total natriuresis was 425 ± 234 mmol. Allocation to acetazolamide strongly and independently predicted natriuresis with a 16 mmol/L (19%) increase in UNa and 115 mmol (32%) greater total natriuresis. Higher systolic blood pressure, better renal function, higher serum sodium levels, and male sex also independently predicted both a higher UNa and greater total natriuresis. A stronger natriuretic response was associated with faster and more complete relief of signs of volume overload, and this effect was already significant on the first morning of assessment (P = 0.022). A significant interaction was observed between the effect of allocation to acetazolamide and UNa on decongestion (P = 0.007). Stronger natriuresis with better decongestion translated into a shorter hospital stay (P < 0.001). After multivariable adjustments, every 10 mmol/L UNa increase was independently associated with a lower risk of all-cause death or heart failure readmission (HR: 0.92; 95% CI: 0.85-0.99).<br /><b>Conclusions</b><br />Increased natriuresis is strongly related to successful decongestion with acetazolamide in ADHF. UNa may be an attractive measure of effective decongestion for future trials. (Acetazolamide in Decompensated Heart Failure with Volume Overload [ADVOR]; NCT03505788).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 23 May 2023; 81:2013-2024</small></div>

<div><h4>Financial Toxicity of Medical Management of Heart Failure: JACC Review Topic of the Week.</h4><i>Sukumar S, Wasfy JH, Januzzi JL, Peppercorn J, Chino F, Warraich HJ</i><br /><AbstractText>Optimal medical management of heart failure (HF) improves quality of life, decreases mortality, and decreases hospitalizations. Cost may contribute to suboptimal adherence to HF medications, especially angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors. Patients\' experiences with HF medication cost include financial burden, financial strain, and financial toxicity. Although there has been research studying financial toxicity in patients with some chronic diseases, there are no validated tools for measuring financial toxicity of HF, and very few data on the subjective experiences of patients with HF and financial toxicity. Strategies to decrease HF-associated financial toxicity include making systemic changes to minimize cost sharing, optimizing shared decision-making, implementing policies to lower drug costs, broadening insurance coverage, and using financial navigation services and discount programs. Clinicians may also improve patient financial wellness through various strategies in routine clinical care. Future research is needed to study financial toxicity and associated patient experiences for HF.</AbstractText><br /><br />Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 23 May 2023; 81:2043-2055</small></div>

<div><h4>Dapagliflozin and diuretic utilization in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial.</h4><i>Chatur S, Vaduganathan M, Claggett B, Vardeny O, ... McMurray JJV, Solomon SD</i><br /><b>Aims</b><br />Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure with mildly reduced or preserved ejection fraction. In this study, the safety and efficacy of dapagliflozin according to background diuretic therapy and the influence of dapagliflozin on longitudinal diuretic use were evaluated.<br /><b>Methods and results</b><br />In this pre-specified analysis of the Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, the effects of dapagliflozin vs. placebo were assessed in the following subgroups: no diuretic, non-loop diuretic, and loop diuretic furosemide equivalent doses of <40, 40, and >40 mg, respectively. Of the 6263 randomized patients, 683 (10.9%) were on no diuretic, 769 (12.3%) were on a non-loop diuretic, and 4811 (76.8%) were on a loop diuretic at baseline. Treatment benefits of dapagliflozin on the primary composite outcome were consistent by diuretic use categories (Pinteraction = 0.64) or loop diuretic dose (Pinteraction = 0.57). Serious adverse events were similar between dapagliflozin and placebo arms, irrespective of diuretic use or dosing. Dapagliflozin reduced new initiation of loop diuretics by 32% [hazard ratio (HR) 0.68; 95% confidence interval (CI): 0.55-0.84, P < 0.001] but did not influence discontinuations/disruptions (HR 0.98; 95% CI: 0.86-1.13, P = 0.83) in follow-up. First sustained loop diuretic dose increases were less frequent, and sustained dose decreases were more frequent in patients treated with dapagliflozin: net difference of -6.5% (95% CI: -9.4 to -3.6; P < 0.001). The mean dose of loop diuretic increased over time in the placebo arm, a longitudinal increase that was significantly attenuated with treatment with dapagliflozin (placebo-corrected treatment effect of -2.5 mg/year; 95% CI: -1.5, -3.7, P < 0.001).<br /><b>Conclusion</b><br />In patients with heart failure with mildly reduced or preserved ejection fraction, the clinical benefits of dapagliflozin relative to placebo were consistent across a wide range of diuretic categories and doses with a similar safety profile. Treatment with dapagliflozin significantly reduced new loop diuretic requirement over time.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 23 May 2023; epub ahead of print</small></div>

<div><h4>Heart failure, peripheral artery disease, and dapagliflozin: a patient-level meta-analysis of DAPA-HF and DELIVER.</h4><i>Butt JH, Kondo T, Yang M, Jhund PS, ... Solomon SD, McMurray JJV</i><br /><b>Aims</b><br />Because an increased risk of amputation with canagliflozin was reported in the CANVAS trials, there has been a concern about the safety of sodium-glucose cotransporter 2 inhibitors in patients with peripheral artery disease (PAD) who are at higher risk of amputation.<br /><b>Methods and results</b><br />A patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the efficacy and safety of dapagliflozin in patients with heart failure (HF) with reduced, mildly reduced/preserved ejection fraction, respectively, was conducted. In both trials, the primary outcome was the composite of worsening HF or cardiovascular death, and amputation was a prespecified safety outcome. Peripheral artery disease history was available for 11 005 of the total 11 007 patients. Peripheral artery disease was reported in 809 of the 11 005 patients (7.4%). Median follow-up was 22 months (interquartile range 17-30). The rate of the primary outcome (per 100 person-years) was higher in PAD patients than that in non-PAD patients: 15.1 [95% confidence interval (CI) 13.1-17.3) vs. 10.6 (10.2-11.1]; adjusted hazard ratio 1.23 (95% CI 1.06-1.43). The benefit of dapagliflozin on the primary outcome was consistent in patients with [hazard ratio 0.71 (95% CI 0.54-0.94)] and without PAD [0.80 (95% CI 0.73-0.88)] (Pinteraction = 0.39). Amputations, while more frequent in PAD patients, were not more common with dapagliflozin, compared with placebo, irrespective of PAD status (PAD, placebo 4.2% vs. dapagliflozin 3.7%; no PAD, placebo 0.4% vs. dapagliflozin 0.4%) (Pinteraction = 1.00). Infection rather than ischaemia was the main trigger for amputation, even in patients with PAD.<br /><b>Conclusion</b><br />The risk of worsening HF or cardiovascular death was higher in patients with PAD, as was the risk of amputation. The benefits of dapagliflozin were consistent in patients with and without PAD, and dapagliflozin did not increase the risk of amputation.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 23 May 2023; epub ahead of print</small></div>

<div><h4>Comparison of Pulmonary Congestion severity using AI-assisted scoring vs. clinical experts: A Secondary Analysis of BLUSHED-AHF.</h4><i>Goldsmith AJ, Jin M, Lucassen R, Duggan NM, ... Pang P, Russell FM</i><br /><b>Background</b><br />Acute decompensated heart failure (ADHF) is the leading cause of cardiovascular hospitalizations in the United States. Detecting B-lines through lung ultrasound (LUS) can enhance clinicians\' prognostic and diagnostic capabilities. Artificial Intelligence/Machine Learning (AI/ML)-based automated guidance systems may allow novice users to apply LUS to clinical care.<br /><b>Aim</b><br />We investigated whether an AI/ML automated LUS congestion score correlates with expert\'s interpretations of B-line quantification from an external patient dataset.<br /><b>Methods</b><br />This was a secondary analysis from the BLUSHED-AHF study which investigated the effect of LUS-guided therapy on patients with ADHF. In BLUSHED-AHF, LUS was performed and B-lines were quantified by ultrasound operators. Two experts then separately quantified the number of B-lines per ultrasound video clip recorded. Here, an AI/ML-based lung congestion score (LCS) was calculated for all LUS clips from BLUSHED-AHF. Spearman correlation was computed between LCS and counts from each of the original three raters.<br /><b>Results</b><br />A total of 3,858 LUS clips were analyzed on 130 patients. The LCS demonstrated good agreement with the two experts\' B-line quantification score (r=0.894, 0.882). Both experts\' B-line quantification scores had significantly better agreement with the LCS than they did with the ultrasound operator\'s score (p<0.005, p<0.001).<br /><b>Conclusion</b><br />AI/ML-based LCS correlated with expert-level B-line quantification. Future studies are needed to determine whether automated tools may assist novice users in LUS interpretation. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 23 May 2023; epub ahead of print</small></div>

<div><h4>Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.</h4><i>Fu S, Inampudi C, Ramu B, Gregoski MJ, ... Cogswell RJ, Tedford RJ</i><br /><b>Background</b><br />While heart transplantation is the gold standard therapy for end-stage heart failure, rates of donor heart utilization remain low due to various factors that are often not evidence-based. The impact of donor hemodynamics obtained via right heart catheterization on recipient survival remains unclear.<br /><b>Methods</b><br />The United Network for Organ Sharing (UNOS) registry was used to identify donors and recipients from September 1999 to December 2019. Donor hemodynamic data were obtained and analyzed using univariate and multivariable logistical regression with the primary endpoints being 1- and 5-year post-transplant survival.<br /><b>Results</b><br />Among the 85,333 donors consented for heart transplantation during the study period, 6,573 (7.7%) underwent right heart catheterization, of which 5,531 eventually underwent procurement and transplantation. Donors were more likely to undergo right heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had similar 1- and 5-year survival to those without donor hemodynamic assessment (87% vs 86%, 1-year).<br /><b>Conclusions</b><br />Abnormal hemodynamics were common in donor hearts but did not impact recipient survival, even when risk-adjusted in multivariable analysis. Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 23 May 2023; epub ahead of print</small></div>

<div><h4>Association Between Change in Ambulatory Pulmonary Artery Pressures and Natriuretic Peptides in Patients with Heart Failure: Results from the EMBRACE-HF Trial.</h4><i>Nassif ME, Nguyen D, Spertus JA, Gosch KL, ... Sauer AJ, Kosiborod MN</i><br /><b>Background</b><br />Remote monitoring of pulmonary artery (PA) pressures and serial NT-proBNP measurements guide heart failure (HF) treatment, but their association has yet to be described.<br /><b>Methods</b><br />In the Empagliflozin Evaluation by Measuring the Impact on Hemodynamics in Patients with Heart Failure (EMBRACE-HF) trial, patients with HF and a remote PA pressure monitoring device were randomized to empagliflozin versus placebo. PA diastolic pressures (PADP) and NT-proBNP levels were obtained at baseline, 6 and 12 weeks. We used linear mixed models to examine the association between change in PADP and change in NT-proBNP, adjusting for baseline covariates.<br /><b>Results</b><br />Of 62 patients, the mean age was 66.2 years, and 63% were male. The mean baseline PADP was 21.8 ± 6.4 mmHg, and the mean NT-proBNP was 1844.6 ± 2767.7 ρg/mL. The mean change between baseline and averaged 6- and 12-week PADP was -0.4 ± 3.1 mmHg, and the mean change between baseline and averaged 6- and 12-week NT-proBNP was -81.5 ± 878.6 ρg/mL. In adjusted analyses, every two mmHg decrease in PADP was associated with an NT-proBNP reduction of 108.9 ρg/mL (95% CI -4.3-222.0, p = 0.06).<br /><b>Conclusion</b><br />We observed that short-term reductions in ambulatory PADP appear to be associated with decreases in NT-proBNP. This finding may provide additional clinical context when tailoring treatment for patients with heart failure.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 23 May 2023; epub ahead of print</small></div>

<div><h4>Increased arterial stiffness elevates the risk of heart failure in diabetic patients.</h4><i>Wu L, Wu M, Zhang X, Chen S, ... Zhuang J, Hong J</i><br /><b>Background</b><br />Previous studies have shown that arterial stiffness (AS) was a risk factor for heart failure (HF) in nondiabetic patients. We aimed to analyze this impact in a community-based diabetic population.<br /><b>Methods</b><br />Our study excluded those who had HF before brachial-ankle pulse wave velocity (baPWV) measurement and included 9041 participants finally. Subjects were divided into the normal (<14 m/s), intermediate (14-18 m/s), and elevated baPWV groups (>18 m/s) based on baPWV values. Multivariate Cox proportional hazard model was used to analyze the effect of AS on HF risk.<br /><b>Results</b><br />During the median follow-up of 4.19 years, 213 patients had HF. The results of Cox model showed that HF risk in the elevated baPWV group was 2.25 times higher than that in the normal baPWV group (95% confidence interval [CI]: 1.24-4.11). HF risk increased by 18% (95% CI:1.03-1.35) for every 1 additional standard deviation(SD)of baPWV. Restricted cubic spline results showed statistically significant overall and non-linear associations between AS and HF risk (P < 0.05). The subgroup analysis and sensitivity analysis were consistent with that of total population.<br /><b>Conclusions</b><br />AS is an independent risk factor for developing HF in the diabetic population, and AS exhibits a dose-response relationship with HF risk.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 23 May 2023; epub ahead of print</small></div>

<div><h4>Coronary revascularization for heart failure with coronary artery disease: a systematic review and meta-analysis of randomized trials.</h4><i>Iaconelli A, Pellicori P, Dolce P, Busti M, ... Crea F, Cleland JG</i><br /><b>Background:</b><br/>and aims</b><br />Coronary artery disease (CAD) is a common cause of heart failure (HF). Whether coronary revascularisation improves outcomes in patients with HF receiving guideline-recommended pharmacological therapy (GRPT) remains uncertain; therefore, we conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs).<br /><b>Methods</b><br />We searched in public databases for RCTs published between 1<sup>st</sup> January 2001 and 22<sup>nd</sup> November 2022, investigating the effects of coronary revascularisation on morbidity and mortality in patients with chronic HF due to CAD. All-cause mortality was the primary outcome.<br /><b>Results</b><br />We included five RCTs that enrolled, altogether, 2,842 patients (most aged <65 years; 85% men; 67% with left ventricular ejection fraction ≤35%). Overall, compared to medical therapy alone, coronary revascularisation was associated with a lower risk of all-cause mortality (HR 0.88 [95% CI, 0.79-0.99]; p=0.0278) and cardiovascular mortality (HR 0.80 [95% CI, 0.70-0.93]; p=0.0024) but not the composite of hospitalisation for HF or all-cause mortality (HR 0.87 [95% CI, 0.74-1.01]; p=0.0728). There were insufficient data to show whether the effect of CABG or PCI were similar or differed.<br /><b>Conclusions</b><br />For patients with chronic HF and CAD enrolled in RCTs, the effect of coronary revascularization on all-cause mortality was statistically significant but neither substantial (HR 0.88) nor robust (upper 95% CI close to 1.0). RCTs were not blinded, which may bias reporting of the cause-specific reasons for hospitalization and mortality. Further trials are required to determine which patients with HF and CAD obtain a substantial benefit from coronary revascularization by either CABG or PCI. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 22 May 2023; epub ahead of print</small></div>

<div><h4>Long-Term Outcomes of Early Coronary Artery Disease Testing After New-Onset Heart Failure.</h4><i>Zheng J, Heidenreich PA, Kohsaka S, Fearon WF, Sandhu AT</i><br /><b>Background</b><br />Coronary artery disease (CAD) testing remains underutilized in patients with newly diagnosed heart failure (HF). The longitudinal clinical impact of early CAD testing has not been well-characterized. We investigated changes in clinical management and long-term outcomes after early CAD evaluation in patients with incident HF.<br /><b>Methods</b><br />We identified Medicare patients with incident HF from 2006 to 2018. The exposure variable was early CAD testing within 1 month of initial HF diagnosis. Covariate-adjusted rates of cardiovascular interventions after testing, including CAD-related management, were modeled using mixed-effects regression with clinician as a random intercept. We assessed mortality and hospitalization outcomes using landmark analyses with inverse probability-weighted Cox proportional hazards models. Falsification end points and mediation analysis were employed for bias assessment.<br /><b>Results</b><br />Among 309 559 patients with new-onset HF without prior CAD, 15.7% underwent early CAD testing. Patients who underwent prompt CAD evaluation had higher adjusted rates of subsequent antiplatelet/statin prescriptions and revascularization, guideline-directed therapy for HF, and stroke prophylaxis for atrial fibrillation/flutter than controls. In weighted Cox models, 1-month CAD testing was associated with significantly reduced all-cause mortality (hazard ratio, 0.93 [95% CI, 0.91-0.96]). Mediation analyses indicated that ≈70% of this association was explained by CAD management, largely from new statin prescriptions. Falsification end points (outpatient diagnoses of urinary tract infection and hospitalizations for hip/vertebral fracture) were nonsignificant.<br /><b>Conclusions</b><br />Early CAD testing after incident HF was associated with a modest mortality benefit, driven mostly by subsequent statin therapy. Further investigation on clinician barriers to testing and treating high-risk patients may improve adherence to guideline-recommended cardiovascular interventions.<br /><br /><br /><br /><small>Circ Heart Fail: 22 May 2023:e010426; epub ahead of print</small></div>

<div><h4>Renal and Blood Pressure Effects of Dapagliflozin in Recently Hospitalized Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction: Insights from the DELIVER Trial.</h4><i>Chatur S, Cunningham JW, Vaduganathan M, Mc Causland FR, ... McMurray JJV, Solomon SD</i><br /><b>Background</b><br />Patients recently hospitalized for heart failure (HF) often have unstable hemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF events. In DELIVER, dapagliflozin reduced HF events or cardiovascular death including among patients who were hospitalized or recently hospitalized.<br /><b>Methods</b><br />We examined the effects of dapagliflozin vs. placebo on eGFR slope (acute and chronic), 1 month change in systolic blood pressure (SBP), and the occurrence of serious hypovolemic or renal adverse events in patients with and without HF hospitalization within 30 days of randomization.<br /><b>Results</b><br />The 654 (90 randomized during hospitalization, 147 1-7 days post-discharge and 417 8-30 days post-discharge) recently hospitalized patients had lower baseline eGFR compared with those without recent HF hospitalization median[IQR] of 55 [43,71] vs 60 [47,75] ml/min/1.73m<sup>2</sup> ). Dapagliflozin consistently reduced the risk of all-cause (P<sub>interaction</sub> =0.20), cardiac-related (P<sub>interaction</sub> =0.75), and HF-specific (P<sub>interaction</sub> =0.90) hospitalizations, irrespective of recent HF hospitalization. In those recently hospitalized, acute placebo-corrected eGFR reductions with dapagliflozin were modest and similar to patients without recent hospitalization (-2.0 [-4.1,+0.1] vs. -3.4 [-3.9,-2.9] ml/min/1.73m<sup>2</sup> , P<sub>interaction</sub> =0.12). Dapagliflozin\'s effect to slow chronic eGFR decline was similar regardless of recent hospitalization (P<sub>interaction</sub> =0.57). Dapagliflozin had a minimal effect on 1-month SBP and to a similar degree in patients with and without recent hospitalization (-1.3 vs.-1.8 mmHg, P<sub>interaction</sub> =0.64). There was no treatment-related excess in renal or hypovolemic serious AE, irrespective of recent HF hospitalization.<br /><b>Conclusion</b><br />In patients recently hospitalized with HF, initiation of dapagliflozin had minimal effects on BP and did not increase renal or hypovolemic serious AEs, yet afforded long-term cardiovascular and kidney protective effects. These data suggest that the benefit to risk ratio favours initiation of dapagliflozin among stabilized patients hospitalized or recently hospitalized for HF. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 22 May 2023; epub ahead of print</small></div>

<div><h4>Contemporary Use of Sodium-Glucose Cotransporter-2 Inhibitor Therapy Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in the US: The Get With The Guidelines-Heart Failure Registry.</h4><i>Pierce JB, Vaduganathan M, Fonarow GC, Ikeaba U, ... Yancy CW, Greene SJ</i><br /><b>Importance</b><br />Clinical guidelines for patients with heart failure with reduced ejection fraction (HFrEF) strongly recommend treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) to reduce cardiovascular mortality or HF hospitalization. Nationwide adoption of SGLT2i for HFrEF in the US is unknown.<br /><b>Objective</b><br />To characterize patterns of SGLT2i use among eligible US patients hospitalized for HFrEF.<br /><b>Design, setting, and participants</b><br />This retrospective cohort study analyzed 49 399 patients hospitalized for HFrEF across 489 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry between July 1, 2021, and June 30, 2022. Patients with an estimated glomerular filtration rate less than 20 mL/min/1.73 m2, type 1 diabetes, and previous intolerance to SGLT2i were excluded.<br /><b>Main outcomes and measures</b><br />Patient-level and hospital-level prescription of SGLT2i at hospital discharge.<br /><b>Results</b><br />Of 49 399 included patients, 16 548 (33.5%) were female, and the median (IQR) age was 67 (56-78) years. Overall, 9988 patients (20.2%) were prescribed an SGLT2i. SGLT2i prescription was less likely among patients with chronic kidney disease (CKD; 4550 of 24 437 [18.6%] vs 5438 of 24 962 [21.8%]; P < .001) but more likely among patients with type 2 diabetes (T2D; 5721 of 21 830 [26.2%] vs 4262 of 27 545 [15.5%]; P < .001) and those with both T2D and CKD (2905 of 12 236 [23.7%] vs 7078 vs 37 139 [19.1%]; P < .001). Patients prescribed SGLT2i therapy were more likely to be prescribed background triple therapy with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, β-blocker, and mineralocorticoid receptor antagonist (4624 of 9988 [46.3%] vs 10 880 of 39 411 [27.6%]; P < .001), and 4624 of 49 399 total study patients (9.4%) were discharged with prescriptions for quadruple medical therapy including SGLT2i. Among 461 hospitals with 10 or more eligible discharges, 19 hospitals (4.1%) discharged 50% or more of patients with prescriptions for SGLT2i, whereas 344 hospitals (74.6%) discharged less than 25% of patients with prescriptions for SGLT2i (including 29 [6.3%] that discharged zero patients with SGLT2i prescriptions). There was high between-hospital variance in the rate of SGLT2i prescription in unadjusted models (median odds ratio, 2.53; 95% CI, 2.36-2.74) and after adjustment for patient and hospital characteristics (median odds ratio, 2.51; 95% CI, 2.34-2.71).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, prescription of SGLT2i at hospital discharge among eligible patients with HFrEF was low, including among patients with comorbid CKD and T2D who have multiple indications for therapy, with substantial variation among US hospitals. Further efforts are needed to overcome implementation barriers and improve use of SGLT2i among patients with HFrEF.<br /><br /><br /><br /><small>JAMA Cardiol: 22 May 2023; epub ahead of print</small></div>

<div><h4>Effect of Torsemide vs Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.</h4><i>Greene SJ, Velazquez EJ, Anstrom KJ, Clare RM, ... Mentz RJ, TRANSFORM-HF Investigators</i><br /><AbstractText><b>Background:</b> Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As pre-specified secondary endpoints, the TRANSFORM-HF trial compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. <br /><b>Methods:</b><br/>TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2,859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomized in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on pre-specified secondary endpoints, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (PHQ-2) (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months. <br /><b>Results:</b><br/>Baseline data were available for 2,787 (97.5%) patients for KCCQ-CSS and 2,624 (91.8%) patients for PHQ-2. Median baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12-months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference 0.06 [95% CI, -2.26 to 2.37]; <i>P</i>=0.96) or the proportion of patients with PHQ-2 score ≥3 (15.1% vs 13.2%: <i>P</i>=0.34). Results for KCCQ-CSS were similar at 1-month (adjusted mean difference 1.36 [95% CI, -0.64 to 3.36]; <i>P</i>=0.18) and 6-month follow-up (adjusted mean difference -0.37 [95% CI, -2.52 to 1.78]; <i>P</i>=0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent prior to hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. <b>Conclusions:</b> Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, prior loop diuretic use, and baseline health status.</AbstractText><br /><br /><br /><br /><small>Circulation: 22 May 2023; epub ahead of print</small></div>

<div><h4>Telemonitoring for heart failure: a meta-analysis.</h4><i>Scholte NTB, Gürgöze MT, Aydin D, Theuns DAMJ, ... van der Boon RMA, Brugts JJ</i><br /><b>Aims</b><br />Telemonitoring modalities in heart failure (HF) have been proposed as being essential for future organization and transition of HF care, however, efficacy has not been proven. A comprehensive meta-analysis of studies on home telemonitoring systems (hTMS) in HF and the effect on clinical outcomes are provided.<br /><b>Methods and results</b><br />A systematic literature search was performed in four bibliographic databases, including randomized trials and observational studies that were published during January 1996-July 2022. A random-effects meta-analysis was carried out comparing hTMS with standard of care. All-cause mortality, first HF hospitalization, and total HF hospitalizations were evaluated as study endpoints. Sixty-five non-invasive hTMS studies and 27 invasive hTMS studies enrolled 36 549 HF patients, with a mean follow-up of 11.5 months. In patients using hTMS compared with standard of care, a significant 16% reduction in all-cause mortality was observed [pooled odds ratio (OR): 0.84, 95% confidence interval (CI): 0.77-0.93, I2: 24%], as well as a significant 19% reduction in first HF hospitalization (OR: 0.81, 95% CI 0.74-0.88, I2: 22%) and a 15% reduction in total HF hospitalizations (pooled incidence rate ratio: 0.85, 95% CI 0.76-0.96, I2: 70%).<br /><b>Conclusion</b><br />These results are an advocacy for the use of hTMS in HF patients to reduce all-cause mortality and HF-related hospitalizations. Still, the methods of hTMS remain diverse, so future research should strive to standardize modes of effective hTMS.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 22 May 2023; epub ahead of print</small></div>

<div><h4>Conventional heart failure therapy in cardiac ATTR amyloidosis.</h4><i>Ioannou A, Massa P, Patel RK, Razvi Y, ... Gillmore JD, Fontana M</i><br /><b>Background:</b><br/>and aims</b><br />The aims of this study were to assess prescription patterns, dosages, discontinuation rates and association with prognosis of conventional heart failure (HF) medications in patients with transthyretin cardiac amyloidosis (ATTR-CA).<br /><b>Methods</b><br />A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000-2022 identified 2371 patients with ATTR-CA.<br /><b>Results</b><br />Prescription of HF medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin-II receptor blockers (ARB) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (IQR 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARB discontinued. In contrast, only 7.5% had MRAs discontinued. Propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population (HR 0.77 [95% CI 0.66-0.89], P<0.001) and in a pre-specified subgroup of patients with a left ventricular ejection fraction (LVEF) >40% (HR 0.75 [95% CI 0.63-0.90], P=0.002); and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% (HR 0.61 [95% CI 0.45-0.83], P=0.002). No convincing differences were found for treatment with ACEi/ARBs.<br /><b>Conclusions</b><br />Conventional HF medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 22 May 2023; epub ahead of print</small></div>

<div><h4>NT-proBNP and high-intensity care for acute heart failure: the STRONG-HF trial.</h4><i>Adamo M, Pagnesi M, Mebazaa A, Davison B, ... Cotter G, Metra M</i><br /><b>Background:</b><br/>and aims</b><br />STRONG-HF showed that rapid up-titration of guideline-recommended medical therapy (GRMT), in a high intensity care (HIC) strategy, was associated with better outcomes compared to usual care (UC). The aim of this study was to assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and its changes early during up-titration.<br /><b>Methods</b><br />A total of 1077 patients hospitalized for acute heart failure (HF) and with a >10% NT-proBNP decrease from screening (i.e. admission) to randomization (i.e. pre-discharge), were included. Patients in HIC were stratified by further NT-proBNP changes from randomization to 1 week later as decreased (≥30% decrease), stable (<30% decrease to ≤10% increase) or increased (>10% increase). The primary endpoint was 180-day HF readmission or death.<br /><b>Results</b><br />The effect of HIC vs. UC was independent of baseline NT-proBNP. Patients in the HIC group with stable or increased NT-proBNP were older, with more severe acute HF and worse renal and liver function. Per protocol, patients with increased NT-proBNP received more diuretics and were up-titrated more slowly during the first weeks after discharge. However, by 6 months they reached 70.4% optimal GRMT doses, compared with 80.3% for those with NT-proBNP decrease. As a result, the primary endpoint at 60 and 90 days occurred in 8.3% and 11.1% of patients with increased NT-proBNP vs 2.2% and 4.0% in those with decreased NT-proBNP (p=0.039 and p=0.045, respectively). However, no difference in outcome was found at 180 days (13.5% vs. 13.2%; p=0.93).<br /><b>Conclusions</b><br />Among patients with acute HF enrolled in STRONG-HF, HIC reduced 180-day HF readmission or death regardless of baseline NT-proBNP. GRMT up-titration early post-discharge utilizing increased NT-proBNP as guidance to increase diuretic therapy and reduce the GRMT up-titration rate resulted in the same 180-day outcomes regardless of early post-discharge NT-proBNP change.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 22 May 2023; epub ahead of print</small></div>

<div><h4>Association of High-Priority Exceptions with Waitlist Mortality Among Heart Transplant Candidates.</h4><i>Johnson DY, Ahn D, Lazenby K, Zeng S, ... Khush K, Parker WF</i><br /><b>Background</b><br />The US heart allocation system ranks candidates using six categorical status levels. Transplant programs can request exceptions to increase a candidate\'s status level if they believe their candidate has the same medical urgency as candidates who meet the standard criteria for that level. We aimed to determine if exception candidates have the same medical urgency as standard candidates.<br /><b>Methods</b><br />Using the Scientific Registry of Transplant Recipients, we constructed a longitudinal waitlist history dataset of adult heart-only transplant candidates listed between October 18, 2018 and December 1, 2021. We estimated the association between exceptions and waitlist mortality with a mixed-effects Cox proportional hazards model that treated status and exceptions as time-dependent covariates.<br /><b>Results</b><br />Out of 12,458 candidates listed during the study period, 2,273 (18.2%) received an exception at listing and 1,957 (15.7%) received an exception after listing. After controlling for status, exception candidates had approximately half the risk of waitlist mortality as standard candidates (HR 0.55, 95% CI [0.41, 0.73], p < 0.001). Exceptions were associated with a 51% lower risk of waitlist mortality among Status 1 candidates (HR 0.49, 95% CI [0.27, 0.91], p = 0.023) and a 61% lower risk among Status 2 candidates (HR 0.39, 95% CI [0.24, 0.62], p < 0.001).<br /><b>Conclusions</b><br />Under the new heart allocation policy, exception candidates had significantly lower waitlist mortality than standard candidates, including exceptions for the highest priority statuses. These results suggest that candidates with exceptions, on average, have a lower level of medical urgency than candidates who meet standard criteria.<br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 22 May 2023; epub ahead of print</small></div>

<div><h4>Ventricular Remodeling and Outcomes After Mitral Transcatheter Edge-to-Edge Repair in Heart Failure: The COAPT Trial.</h4><i>Lindman BR, Asch FM, Grayburn PA, Mack MJ, ... Lindenfeld J, Stone GW</i><br /><b>Background</b><br />The relationship between left ventricular (LV) remodeling and clinical outcomes after treatment of severe mitral regurgitation (MR) in heart failure (HF) has not been examined.<br /><b>Objectives</b><br />The aim of this study was to evaluate the association between LV reverse remodeling and subsequent outcomes and assess whether transcatheter edge-to-edge repair (TEER) and residual MR are associated with LV remodeling in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.<br /><b>Methods</b><br />Patients with HF and severe MR who remained symptomatic on guideline-directed medical therapy (GDMT) were randomized to TEER plus GDMT or GDMT alone. Baseline and 6-month core laboratory measurements of LV end-diastolic volume index and LV end-systolic volume index were examined. Change in LV volumes from baseline to 6 months and clinical outcomes from 6 months to 2 years were evaluated using multivariable regression.<br /><b>Results</b><br />The analytical cohort comprised 348 patients (190 treated with TEER, 158 treated with GDMT alone). A decrease in LV end-diastolic volume index at 6 months was associated with reduced cardiovascular death between 6 months and 2 years (adjusted HR: 0.90 per 10 mL/m<sup>2</sup> decrease; 95% CI: 0.81-1.00; P = 0.04), with consistent results in both treatment groups (P<sub>interaction</sub> = 0.26). Directionally similar but nonsignificant relationships were present for all-cause death and HF hospitalization and between reduced LV end-systolic volume index and all outcomes. Neither treatment group nor MR severity at 30 days was associated with LV remodeling at 6 or 12 months. The treatment benefits of TEER were not significant regardless of the degree of LV remodeling at 6 months.<br /><b>Conclusions</b><br />In patients with HF and severe MR, LV reverse remodeling at 6 months was associated with subsequently improved 2-year outcomes but was not affected by TEER or the extent of residual MR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Interv: 22 May 2023; 16:1160-1172</small></div>

<div><h4>Cardio-Renal-Metabolic Overlap, Outcomes, and Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.</h4><i>Ostrominski JW, Thierer J, Claggett BL, Miao ZM, ... Solomon SD, Vaduganathan M</i><br /><b>Background</b><br />Cardio-renal-metabolic (CRM) conditions are individually common among patients with HF, but the prevalence and influence of overlapping CRM conditions in this population have not been well-studied.<br /><b>Objectives</b><br />To evaluate the impact of overlapping CRM conditions on clinical outcomes and treatment effects of dapagliflozin in HF.<br /><b>Methods</b><br />In this post-hoc analysis of DELIVER, we evaluated the prevalence of comorbid CRM conditions (atherosclerotic cardiovascular disease, chronic kidney disease, and type 2 diabetes), their impact on the primary outcome (cardiovascular death or worsening HF), and treatment effects of dapagliflozin by CRM status.<br /><b>Results</b><br />Among 6,263 participants, 1,952 (31%), 2,245 (36%), and 1,236 (20%) had 1, 2, and 3 additional CRM conditions, respectively. HF alone was uncommon (13%). Greater CRM multimorbidity was associated with older age, higher BMI, longer-duration HF, worse health status, and lower LVEF. Risk of the primary outcome increased with higher CRM overlap, with 3 CRM conditions independently associated with highest risk of primary events (adjusted HR, 2.16 [95% CI, 1.72-2.72]; P<0.001) compared with HF alone. Relative benefits of dapagliflozin on the primary outcome were consistent irrespective of the type of CRM overlap (P<sub>interaction</sub>=0.773) and by the number of CRM conditions (P<sub>interaction</sub>=0.734), with greatest absolute benefits among those with highest CRM multimorbidity. Estimated two-year numbers needed to treat with dapagliflozin to prevent one primary event were approximately 52, 39, 33, and 24 for participants with 0, 1, 2, and 3 additional CRM conditions at baseline, respectively. Adverse events between treatment arms were similar across the CRM spectrum.<br /><b>Conclusions</b><br />Cardio-renal-metabolic multimorbidity was common and associated with adverse outcomes among patients with HF and LVEF>40% in DELIVER. Dapagliflozin was safe and effective across the CRM spectrum, with greater absolute benefits among those with highest CRM overlap.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 22 May 2023; epub ahead of print</small></div>

<div><h4>Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE-ICM International Registry.</h4><i>Pontone G, Guaricci AI, Fusini L, Baggiano A, ... Masci PG, Schwitter J</i><br /><b>Background</b><br />Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation.<br /><b>Objectives</b><br />The DERIVATE (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy)-ICM registry (NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM.<br /><b>Methods</b><br />A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints.<br /><b>Results</b><br />During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007).<br /><b>Conclusions</b><br />The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 22 May 2023; epub ahead of print</small></div>

<div><h4>Patient profiles in heart failure with reduced ejection fraction: prevalence, characteristics, treatments and outcomes in a real-world heart failure population.</h4><i>Musella F, Rosano GMC, Hage C, Benson L, ... Lund LH, Savarese G</i><br /><b>Background</b><br />The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guidelines-directed medical treatments according to patient\'s profiles. Aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles.<br /><b>Methods and results</b><br />Patients with heart failure with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013-2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate, eGFR), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The 9 most frequent profiles accounting for 70.5% of the population had eGFR 30-60 or ≥60 mL/min/1.73m<sup>2</sup> , sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30-60 mL/min/1.73m<sup>2</sup> and AF. We also identified 9 profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR <30mL/min/1.73m<sup>2</sup> and AF. The 3 profiles with eGFR 30-60mL/min/1.73m<sup>2</sup> also showed sBP <90mmHg.<br /><b>Conclusions</b><br />In a real-world cohort most patients fit in a few easily identifiable profiles; the 9 profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drugs´ implementation and follow-ups. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Effects of Dapagliflozin on Heart Failure Hospitalizations According to Severity of Inpatient Course: Insights from DELIVER and DAPA-HF.</h4><i>Chatur S, Kondo T, Claggett BL, Docherty K, ... Solomon SD, Vaduganathan M</i><br /><b>Aims</b><br />Dapagliflozin resulted in significant and sustained reductions in first and recurrent HF hospitalizations among patients with HF across the spectrum of ejection fraction. How treatment with dapagliflozin differentially impacts hospitalization for HF of varying complexity is not well studied.<br /><b>Methods and results</b><br />In the DELIVER and DAPA-HF trials, we examined the effects of dapagliflozin on adjudicated HF hospitalizations of varying complexity and hospital length of stay (LOS). HF hospitalizations requiring ICU stay, IV vasoactive therapies, invasive/non-invasive ventilation, mechanical fluid removal or MCS were categorized as complicated. The balance were classified as uncomplicated. Of the total 1209 HF hospitalizations reported in DELIVER, 71% (854) were uncomplicated and 29% (355) were complicated. Of the total 799 HF hospitalizations reported in DAPA-HF, 57% (453) were uncomplicated and 43% (346) were complicated. Relative to patients experiencing a first uncomplicated HF hospitalization, those with complicated HF hospitalizations had a significantly higher in-hospital mortality both in DELIVER (16.8% vs. 2.3%, p < 0.001) and DAPA-HF (15.1% vs. 3.8%, p < 0.001). Dapagliflozin similarly reduced total \'uncomplicated\' (DELIVER: RR 0.67, 95% CI: 0.55-0.82 and DAPA-HF: RR 0.69, 95% CI: 0.54-0.87) and \'complicated\' HF hospitalizations (DELIVER: 0.82, 95% CI: 0.63-1.06 and DAPA-HF: 0.75, 95% CI: 0.58-0.97). Dapagliflozin consistently reduced hospitalizations irrespective of their LOS: <5 days (DELIVER: RR 0.76; 95% CI: 0.58-0.99 and DAPA-HF: 0.58; 95%: 0.42-0.80) or ≥5 days (DELIVER: RR 0.71; 95% CI: 0.58-0.86 and DAPA-HF: 0.77; 95% CI: 0.62-0.94).<br /><b>Conclusion</b><br />A substantial proportion of hospitalizations (~30%-40%) among patients with HF irrespective of ejection fraction required intensification of treatment beyond standard intravenous diuretics. Such patients experienced significantly higher in-hospital mortality. Treatment with dapagliflozin consistently reduced HF hospitalizations regardless of severity of inpatient treatment course or LOS. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Exercise-induced B-lines for the diagnosis of heart failure with preserved ejection fraction: a two-centre study.</h4><i>Coiro S, Echivard M, Simonovic D, Duarte K, ... Ambrosio G, Girerd N</i><br /><b>Background</b><br />Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging despite the use of scores/algorithms. This study intended to assess the diagnostic value of exercise lung ultrasound (LUS) for HFpEF diagnosis.<br /><b>Methods</b><br />We studied two independent case-control studies of HFpEF patients and control subjects undergoing different exercise protocols: (i) submaximal exercise stress echocardiography (ESE) with LUS performed by expert cardiologists (N = 116, HFpEF = 65.5%), and (ii) maximal cycle ergometer test (CET) (N = 54, HFpEF = 50%) with LUS performed by unexperienced physicians shortly trained for the study. B-line kinetics (i.e. peak values and their changes from rest) were assessed.<br /><b>Results</b><br />In the ESE cohort, the C-index (95% CI) of peak B-lines for HFpEF diagnosis was 0.985 (0.968-1.000), whereas the C-index of rest and exercise HFA-PEFF scores (i.e. including stress echo findings) were < 0.90 (CI 0.823-0.949), and that of H2FPEF score was < 0.70 (CI 0.558-0.764). The C-index increase of peak B-lines on top of the above-mentioned scores was significant (C-index increase > 0.090 and P-value < 0.001 for all). Similar results were observed for change B-lines. Peak B-lines > 5 (sensitivity = 93.4%, specificity = 97.5%) and change B-lines > 3 (sensitivity = 94.7%, specificity = 87.5%) were the best cutoffs for HFpEF diagnosis. Adding peak or change B-lines on top of HFpEF scores and BNP significantly improved diagnostic accuracy. Peak B-lines showed a good diagnostic accuracy in the LUS beginner-led CET cohort (C-index = 0.713, 0.588-0.838).<br /><b>Conclusions</b><br />Exercise LUS showed excellent diagnostic value for HFpEF diagnosis regardless of different exercise protocols/level of expertise, with additive diagnostic accuracy on top of available scores and natriuretic peptides.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 21 May 2023; epub ahead of print</small></div>

<div><h4>Dapagliflozin versus metolazone in heart failure resistant to loop diuretics.</h4><i>Ern Yeoh S, Osmanska J, Petrie MC, Brooksbank KJM, ... McMurray JJV, Campbell RT</i><br /><b>Background:</b><br/>and aims</b><br />To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide.<br /><b>Methods</b><br />A multi-centre, open-label, randomized, active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 hours). The primary endpoint was diuretic effect, assessed by change in weight (kg). Secondary endpoints included change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score.<br /><b>Results</b><br />61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 hours was 976 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 hours was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; p=0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) versus 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; p=0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments.<br /><b>Conclusion</b><br />In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone.<br /><b>Clinicaltrials.gov identifier</b><br />NCT04860011.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 21 May 2023; epub ahead of print</small></div>

<div><h4>Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF.</h4><i>Vaduganathan M, Mentz RJ, Claggett BL, Miao ZM, ... Braunwald E, Solomon SD</i><br /><b>Background:</b><br/>and aims</b><br />The PARAGLIDE-HF trial demonstrated reductions in natriuretic peptides with sacubitril/valsartan compared with valsartan in patients with heart failure (HF) with mildly reduced or preserved ejection fraction who had a recent worsening HF event, but was not adequately powered to examine clinical outcomes. PARAGON-HF included a subset of PARAGLIDE-HF-like patients who were recently hospitalized for HF. Participant-level data from PARAGLIDE-HF and PARAGON-HF were pooled to better estimate the efficacy and safety of sacubitril/valsartan in reducing cardiovascular and renal events in HF with mildly reduced or preserved ejection fraction.<br /><b>Methods</b><br />Both PARAGLIDE-HF and PARAGON-HF were multicenter, double-blind, randomized, active-controlled trials of sacubitril/valsartan vs. valsartan in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF >40% in PARAGLIDE-HF and ≥45% in PARAGON-HF). In the pre-specified primary analysis, we pooled participants in PARAGLIDE-HF (all of whom were enrolled during or within 30 days of a worsening HF event) with a \'PARAGLIDE-like\' subset of PARAGON-HF (those hospitalized for HF within 30 days). We also pooled the entire PARAGLIDE-HF and PARAGON-HF populations for a broader context. The primary endpoint for this analysis was the composite of total worsening HF events (including first and recurrent HF hospitalizations and urgent visits) and cardiovascular death. The secondary endpoint was the pre-specified renal composite endpoint for both studies (≥50% decline in estimated glomerular filtration rate from baseline, end-stage renal disease, or renal death).<br /><b>Results</b><br />Compared with valsartan, sacubitril/valsartan significantly reduced total worsening HF events and cardiovascular death in both the primary pooled analysis of participants with recent worsening HF (n=1,088; rate ratio [RR] 0.78; 95% confidence interval [CI] 0.61-0.99; P=0.042) and in the pooled analysis of all participants (n=5,262; RR 0.86; 95% CI: 0.75-0.98; P=0.027). In the pooled analysis of all participants, first nominal statistical significance was reached by day 9 after randomization and treatment benefits were larger in those with LVEF ≤60% (RR 0.78; 95% CI 0.66-0.91) compared with those with LVEF >60% (RR 1.09; 95% CI 0.86-1.40; Pinteraction=0.021). Sacubitril/valsartan was also associated with lower rates of the renal composite endpoint in the primary pooled analysis (hazard ratio [HR] 0.67; 95% CI 0.43-1.05; P=0.080) and the pooled analysis of all participants (HR 0.60; 95% CI 0.44-0.83; P=0.002).<br /><b>Conclusions</b><br />In pooled analyses of PARAGLIDE-HF and PARAGON-HF, sacubitril/valsartan reduced cardiovascular and renal events among patients with HF with mildly reduced or preserved ejection fraction. These data provide support for use of sacubitril/valsartan in patients with HF with mildly reduced or preserved ejection fraction, particularly among those with an LVEF below normal, regardless of care setting.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 21 May 2023; epub ahead of print</small></div>

<div><h4>Efficacy of Pulmonary Artery Pressure Monitoring in Patients with Chronic Heart Failure: A Meta-Analysis of Three Randomized Controlled Trials.</h4><i>Clephas PRD, Radhoe SP, Boersma E, Gregson J, ... de Boer RA, Brugts JJ</i><br /><b>Background:</b><br/>and aims</b><br />Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question.<br /><b>Methods</b><br />A systematic literature search was performed for randomized clinical trials (RCTs) with PA pressure monitoring devices in patients with HF. The primary outcome of interest was the total number of HF hospitalizations. Other outcomes assessed were urgent visits leading to treatment with intravenous diuretics, all-cause mortality, and composites. Treatment effects are expressed as hazard ratios, and pooled effect estimates were obtained applying random effects meta-analyses.<br /><b>Results</b><br />Three eligible RCTs were identified that included 1898 outpatients in New York Heart Association functional class II-IV, either hospitalized for HF in the prior 12 months or with elevated plasma NT-proBNP concentrations. Mean follow-up was 14.7 months, 67.8% of the patients were men, and 65.8% had an ejection fraction ≤40%. Compared to patients in the control group, the hazard ratio (95% confidence interval) for total HF hospitalizations in those randomized to PA pressure monitoring was 0.70 (0.58-0.86) (p=0.0005). The corresponding hazard ratio for the composite of total HF hospitalizations, urgent visits and all-cause mortality was 0.75 (0.61-0.91; p=0.0037) and for all-cause mortality 0.92 (0.73-1.16). Subgroup analyses, including ejection fraction phenotype, revealed no evidence of heterogeneity in the treatment effect.<br /><b>Conclusions</b><br />The use of remote PA pressure monitoring to guide treatment of patients with HF reduces episodes of worsening HF and subsequent hospitalizations.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 21 May 2023; epub ahead of print</small></div>

<div><h4>Prevalence, Characteristics and Prognostic Impact of Aortic Valve Disease in Patients with Heart Failure and Reduced, Mildly Reduced, and Preserved Ejection Fraction: An Analysis of the ESC Heart Failure Long-Term Registry.</h4><i>Shahim B, Shahim A, Adamo M, Chioncel O, ... Metra M, Lund LH</i><br /><b>Aims</b><br />To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (stenosis, AS; regurgitation, AR; mixed MAVD).<br /><b>Methods and results</b><br />Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analyzed. Of 15 216 patients with HF (62.5% reduced EF, HFrEF; 14.0% mildly reduced, HFmrEF; 23.5% preserved, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8% and 3% in HFpEF, 6%, 3% and 2% in HFmrEF and 4%, 3% and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter (LVEDD) with AR. AS (adjusted HR 1.43, 95% CI 1.23-1.67), and MAVD (1.37, 95% CI 1.07-1.75) but not AR (1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of CV death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of EF category.<br /><b>Conclusions</b><br />In the ESC HFA EORP HF Long-Term Registry, one in ten patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all EF categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of EF category. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Impact of Dapagliflozin on cardiac remodeling in patients with chronic heart failure: DAPA-MODA study.</h4><i>Pascual-Figal DA, Zamorano JL, Domingo M, Morillas H, ... Juanatey JRG, Comins MA</i><br /><b>Rationale</b><br />Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless left ventricular ejection fraction (LVEF). However, its effect on cardiac remodeling parameters, specifically left atrial (LA) remodeling, is not well established.<br /><b>Methods</b><br />DAPA-MODA trial (NCT04707352) is a multicenter, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodeling parameters over six months.. Patients with stable chronic heart failure receiving optimized guideline-directed therapy, except for any SGLT2i, were included. Echocardiography was performed at baseline, 30 and 180 days, and analyzed by a central core-lab in a blinded manner to both patient and time. The primary end-point was the change of maximal LA volume index (LAVI).<br /><b>Results</b><br />A total of 162 patients (64.2% men, 70.5±10.6 years, 52% LVEF>40%) were included in the study. At baseline, LA dilatation was observed (LAVI 49.1±24.4 ml/m2) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% (CI95% -11.1, -1.8, p=0.008), primarily due to a decrease in reservoir volume (-13.8%, p=0.007). LV geometry improved with significant reductions in LV mass index (-13.9%, p<0.001), end-diastolic volume (-8.0%, p<0.001) and end-systolic volume (-11.9%, p<0.001) at 180 days. NT-proBNP showed a significant reduction at 180 days (-18.2% [CI95% -27.1, -8.2], p<0.001), without changes in filling doppler measures.<br /><b>Conclusion</b><br />Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodeling of cardiac structure, including reductions in LA volumes and improvement in LV geometry and NT-proBNP concentrations. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Electronic nudges to increase influenza vaccination uptake among patients with heart failure: a prespecified analysis of the NUDGE-FLU trial.</h4><i>Johansen ND, Vaduganathan M, Bhatt AS, Lee SG, ... Krause TG, Biering-Sørensen T</i><br /><b>Aims</b><br />Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE-FLU trial recently found two electronic behavioural nudging letter strategies - a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 - effective in increasing influenza vaccination in Denmark. The aims of this prespecified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off-target effects on guideline-directed medical therapy (GDMT) use.<br /><b>Methods and results</b><br />The nationwide NUDGE-FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or 9 different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022-2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE-FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain-framed letter: p<sub>interaction</sub>  = 0.37; repeated letter: p<sub>interaction</sub>  = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (p<sub>interaction</sub>  = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain-framed letter (p<sub>interaction</sub>  = 0.07). The letters had no impact on longitudinal GDMT use.<br /><b>Conclusions</b><br />Approximately 1 in 4 patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain-framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Effect of Dapagliflozin on Health Status and Quality-of-Life Across the Spectrum of Ejection Fraction: Participant-Level Pooled Analysis from the DAPA-HF & DELIVER Trials.</h4><i>Bhatt AS, Kosiborod MN, Vaduganathan M, Claggett BL, ... McMurray JJV, Solomon SD</i><br /><b>Introduction</b><br />Patients with heart failure experience a high burden of symptoms, physical limitations, and poor quality-of-life. Dapagliflozin improves heart failure hospitalization and cardiovascular death in patients with reduced, mildly reduced, and preserved ejection fractions. We examined the effects of dapagliflozin on health status, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), across the full spectrum of left ventricular ejection fraction (LVEF).<br /><b>Methods</b><br />Participant-level data were pooled from the DAPA-HF and DELIVER trials. Both trials were randomized, global, double-blind, placebo-controlled trials of patients with symptomatic HF and elevated natriuretic peptides. DAPA-HF and DELIVER included patients with LVEF≤40% and LVEF>40%, respectively. KCCQ was evaluated at randomization and at 8-months post randomization; the effect of dapagliflozin vs. placebo on KCCQ total symptom score (TSS) was a prespecified secondary outcome in both trials. Interaction testing was performed to assess potential heterogeneity in the effects of dapagliflozin vs. placebo on KCCQ TSS, Clinical Summary Score (CSS), Overall Summary Score (OSS), and Physical Limitations Score (PLS), by continuous LVEF using restricted cubic splines. Responder analyses examining the proportion of patients with meaningful deterioration (≥5 point decline) and meaningful improvements (≥5 point increase) in KCCQ-TSS was assessed across LVEF categories.<br /><b>Results</b><br />Of 11 007 patients randomized, 10 238 (93%) had full data on KCCQ-TSS at randomization. Benefits of dapagliflozin vs. placebo on KCCQ-TSS, -CSS, -OSS, -PLS, at 8 months were consistent across the full range of LVEF (P for interactions = 0.19, 0.10, 0.12, 0.10 respectively). In responder analyses, fewer dapagliflozin- vs. placebo-treated patients had clinically meaningful deteriorations in KCCQ-TSS (Overall: 21% vs. 23%; LVEF≤40%: 21% vs. 29%; LVEF 41%-60%: 21% vs. 26%; LVEF>60%: 22% vs. 27%). A greater proportion of patients randomized to dapagliflozin experienced meaningful improvements in KCCQ-TSS (Overall: 50% vs. 45%; LVEF≤40%: 48% vs. 41%; LVEF 41%-60%: 51% vs. 49%; LVEF>60%: 53% vs. 45%). The effects of dapagliflozin vs. placebo on clinically meaningful deteriorations and improvements in health status by KCCQ-TSS were consistent across the full spectrum of LVEF assessed continuously (p for interaction: 0.20 and 0.64, respectively). Across the LVEF spectrum, the number-needed-to-treat to affect ≥5 point improvement in health status assessed by KCCQ-TSS was 20. Health status declines preceeding a HF hospitalization by approximately 10 points on average were observed in both trials, evident up to 3 months prior to the event.<br /><b>Conclusions</b><br />In participant-level pooled analyses of DAPA-HF and DELIVER, dapagliflozin improved all key domains of health status across the full range of LVEF. Clinically meaningful improvements in health status were also observed consistently across the full range of LVEF, including in those with LVEF above 60%. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Fewer worsening heart failure events with HeartLogic on top of standard of care: a propensity-matched cohort analysis.</h4><i>Feijen M, Beles M, Tan YZ, Cordon A, ... Beeres SLMA, Heggermont WA</i><br /><b>Background</b><br />The implantable cardiac defibrillator (ICD) based HeartLogic<sup>TM</sup> algorithm aims to detect impending fluid retention in heart failure (HF) patients. Studies show that HeartLogic<sup>TM</sup> is safe to integrate in clinical practice. The current study investigates if HeartLogic<sup>TM</sup> provides clinical benefit on top of standard care and device telemonitoring in HF patients.<br /><b>Methods</b><br />A multicenter retrospective propensity-matched cohort analysis was performed in HF patients with and ICD and compared HeartLogic<sup>TM</sup> to conventional telemonitoring. Primary endpoint was the number of worsening HF events. HF hospitalizations and ambulatory HF visits were also evaluated.<br /><b>Results</b><br />Propensity score matching yielded 127 pairs (median age 68 years, 80% male). Worsening HF events occurred more frequently in the control group (2, IQR 0-4) compared to the HeartLogic<sup>TM</sup> group (1, IQR 0-3, p=0.004). The number of HF hospitalization days was higher in controls compared to the HeartLogic<sup>TM</sup> group (8, IQR 5-12 vs. 5, IQR 2-7, p=0.023) and ambulatory visits for diuretic escalation were more frequent in the control group than in the HeartLogic<sup>TM</sup> group (2, IQR 0-3 vs. 1, IQR 0-2, p=0.0001).<br /><b>Conclusion</b><br />Integrating the HeartLogic<sup>TM</sup> algorithm in a well-equipped HF care path on top of standard care, is associated with fewer worsening HF events and shorter duration of fluid retention related hospitalizations.<br /><br />Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Association Between Participation in a Heart Failure Telemonitoring Program and Healthcare Utilization and Death within an Integrated Health Care Delivery System.</h4><i>Parikh RV, Axelrod AW, Ambrosy AP, Tan TC, ... Dinh HH, Go AS</i><br /><b>Background</b><br />The clinical utility of remote telemonitoring to reduce post-discharge healthcare utilization and death in adults with heart failure (HF) remains controversial.<br /><b>Methods and results</b><br />Within a large integrated health care delivery system, we matched patients enrolled in a post-discharge telemonitoring intervention from 2015-2019 to patients not receiving telemonitoring at up to a 1:4 ratio on age, sex, and calipers of a propensity score. Primary outcomes were readmissions for worsening heart failure (WHF) and all-cause death within 30, 90, and 365 days of index discharge; secondary outcomes were all-cause readmissions and any outpatient diuretic dose adjustments. We matched 726 patients receiving telemonitoring to 1985 controls not receiving telemonitoring, with a mean (SD) age of 75 (11) years and 45% female. Patients receiving telemonitoring did not have a significant reduction in WHF hospitalizations (adjusted rate ratio [aRR]: 0.95, 95% confidence interval [CI]: 0.68, 1.33), all-cause death (adjusted hazard ratio: 0.60, 95% CI: 0.33, 1.08), or all-cause hospitalization (aRR: 0.82, 95% CI: 0.65, 1.05) at 30 days, but did have an increase in outpatient diuretic dose adjustments (aRR: 1.84, 95% CI: 1.44, 2.36). All associations were similar at 90- and 365-days post-discharge.<br /><b>Conclusions</b><br />A post-discharge HF telemonitoring intervention was associated with more diuretic dose adjustments but was not significantly associated with HF-related morbidity and mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Association of Dapagliflozin vs Placebo With Individual Kansas City Cardiomyopathy Questionnaire Components in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the DELIVER Trial.</h4><i>Peikert A, Chandra A, Kosiborod MN, Claggett BL, ... Solomon SD, Vaduganathan M</i><br /><b>Importance</b><br />Dapagliflozin has been shown to improve overall health status based on aggregate summary scores of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. A comprehensive understanding of the responsiveness of individual KCCQ items would allow clinicians to better inform patients on expected changes in daily living with treatment.<br /><b>Objective</b><br />To examine the association of dapagliflozin treatment with changes in individual components of the KCCQ.<br /><b>Design, setting, and participants</b><br />This is a post hoc exploratory analysis of DELIVER, a randomized double-blind placebo-controlled trial conducted at 353 centers in 20 countries from August 2018 to March 2022. KCCQ was administered at randomization and 1, 4, and 8 months. Scores of individual KCCQ components were scaled from 0 to 100. Eligibility criteria included symptomatic HF with left ventricular ejection fraction greater than 40%, elevated natriuretic peptide levels, and evidence of structural heart disease. Data were analyzed from November 2022 to February 2023.<br /><b>Main outcomes and measures</b><br />Changes in the 23 individual KCCQ components at 8 months.<br /><b>Interventions</b><br />Dapagliflozin, 10 mg, once daily or placebo.<br /><b>Results</b><br />Baseline KCCQ data were available for 5795 of 6263 randomized patients (92.5%) (mean [SD] age, 71.5 [9.5] years; 3344 male [57.7%] and 2451 female [42.3%]). Dapagliflozin was associated with larger improvements in almost all KCCQ components at 8 months compared with placebo. The most significant improvements with dapagliflozin were observed in frequency of lower limb edema (difference, 3.2; 95% CI, 1.6-4.8; P < .001), sleep limitation by shortness of breath (difference, 3.0; 95% CI, 1.6-4.4; P < .001), and limitation in desired activities by shortness of breath (difference, 2.8; 95% CI, 1.3-4.3; P < .001). Similar treatment patterns were observed in longitudinal analyses integrating data from months 1, 4, and 8. Higher proportions of patients treated with dapagliflozin experienced improvements, and fewer had deteriorations across most individual components.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study of patients with HF with mildly reduced or preserved ejection fraction, dapagliflozin was associated with improvement in a broad range of individual KCCQ components, with the greatest benefits in domains related to symptom frequency and physical limitations. Potential improvements in specific symptoms and activities of daily living might be more readily recognizable and easily communicated to patients.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03619213.<br /><br /><br /><br /><small>JAMA Cardiol: 20 May 2023; epub ahead of print</small></div>

<div><h4>Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials.</h4><i>Nassif ME, Windsor SL, Gosch K, Borlaug BA, ... Sharma K, Kosiborod MN</i><br /><b>Background</b><br />Patients with heart failure (HF) have a high burden of symptoms and physical limitations, regardless of ejection fraction (EF). Whether the benefits of SGLT2 (sodium-glucose cotransporter-2) inhibitors on these outcomes vary across the full range of EF remains unclear.<br /><b>Methods</b><br />Patient-level data were pooled from the DEFINE-HF trial (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction) of 263 participants with reduced EF (≤40%), and PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure) of 324 participants with preserved EF (≥45%). Both were randomized, double-blind 12-week trials of dapagliflozin versus placebo, recruiting participants with New York Heart Association class II or higher and elevated natriuretic peptides. The effect of dapagliflozin on the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at 12 weeks was tested with ANCOVA adjusted for sex, baseline KCCQ, EF, atrial fibrillation, estimated glomerular filtration rate, and type 2 diabetes. Interaction of dapagliflozin effects on KCCQ-CSS by EF was assessed using EF both categorically and continuously with restricted cubic spline. Responder analyses, examining proportions of patients with deterioration, and clinically meaningful improvements in KCCQ-CSS were conducted using logistic regression.<br /><b>Results</b><br />Of 587 patients randomized (293 dapagliflozin, 294 placebo), EF was ≤40, >40-≤60, and >60% in 262 (45%), 199 (34%), and 126 (21%), respectively. Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference 5.0 points [95% CI, 2.6-7.5]; <i>P</i><0.001). This was consistent in participants with EF≤40 (4.6 points [95% CI, 1.0-8.1]; <i>P</i>=0.01), >40 to ≤60 (4.9 points [95% CI, 0.8-9.0]; <i>P</i>=0.02) and >60% (6.8 points [95% CI, 1.5-12.1]; <i>P</i>=0.01; <i>P</i><sub>interaction</sub>=0.79). Benefits of dapagliflozin on KCCQ-CSS were also consistent when analyzing EF continuously (<i>P</i><sub>interaction</sub>=0.94). In responder analyses, fewer dapagliflozin-treated patients had deterioration and more had small, moderate, and large KCCQ-CSS improvements versus placebo; these results were also consistent regardless of EF (all <i>P</i><sub>interaction</sub>values nonsignificant).<br /><b>Conclusions</b><br />In patients with HF, dapagliflozin significantly improves symptoms and physical limitations after 12 weeks of treatment, with consistent and clinically meaningful benefits across the full range of EF.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifiers: NCT02653482 and NCT03030235.<br /><br /><br /><br /><small>Circ Heart Fail: 19 May 2023:e009837; epub ahead of print</small></div>

<div><h4>Changes in health-related quality of life and treatment effects in chronic heart failure: A meta-analysis.</h4><i>Angélico-Gonçalves A, Leite AR, Neves JS, Saraiva F, ... Leite-Moreira A, Ferreira JP</i><br /><b>Background</b><br />Heart failure (HF) is associated with poor health status, and high morbi-mortality. However, it is not well established how health status changes correlate with treatment effects on clinical outcomes. Our aim was to study the association between treatment-induced changes in health-status, assessed by Kansas City Cardiomyopathy Questionnaire 23 (KCCQ-23) and clinical outcomes in chronic HF.<br /><b>Methods</b><br />Systematic search of phase III-IV pharmacological RCTs in chronic HF that assessed KCCQ-23 changes and clinical outcomes throughout follow-up. We studied the association between treatment induced changes in KCCQ-23 and treatment effects on clinical outcomes (HF hospitalization or cardiovascular death, HF hospitalization, cardiovascular death, and all-cause death) using weighted random-effects meta-regression.<br /><b>Results</b><br />Sixteen trials were included, enrolling a total of 65,664 participants. Treatment induced KCCQ-23 changes were moderately correlated with treatment effects on the combined outcome of HF hospitalization or cardiovascular mortality (regression coefficient (RC) = -0.047, 95%CI: -0.085 to -0.009; R<sup>2</sup> = 49%), a correlation that was mainly driven by HF hospitalization (RC = -0.076, 95%CI: -0.124 to -0.029; R<sup>2</sup> = 56%). Correlations of treatment induced KCCQ-23 changes with cardiovascular death (RC = -0.029, 95%CI: -0.073 to 0.015; R<sup>2</sup> = 10%) and all-cause death (RC = -0.019, 95%CI: -0.057 to 0.019; R<sup>2</sup> = 0%) were weak and non-significant.<br /><b>Conclusions</b><br />Treatment-induced changes in KCCQ-23 were moderately correlated with treatment-effects on HF hospitalizations but were not correlated with the effects on cardiovascular and all-cause mortality. Treatment-induced changes in patient-centered outcomes (i.e., KCCQ-23) may reflect non-fatal symptomatic changes in the clinical course of HF leading to hospitalization.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 19 May 2023; epub ahead of print</small></div>

<div><h4>Center Case Volume is Associated with Society of Thoracic Surgeons-Defined Failure to Rescue in Cardiac Surgery.</h4><i>Strobel RJ, Young AM, Rotar EP, Kaplan EF, ... Teman NR, Investigators for the Virginia Cardiac Services Quality Initiative</i><br /><b>Objective</b><br />Our understanding of the impact of a center\'s case volume on failure to rescue (FTR) after cardiac surgery is incomplete. We hypothesized that increasing center case volume would be associated with lower FTR.<br /><b>Methods</b><br />Patients undergoing an STS index operation in a regional collaborative (2011-2021) were included. After excluding patients with missing STS predicted risk of mortality, patients were stratified by mean annual center case volume. The lowest quartile of case volume was compared to all other patients. Logistic regression analyzed the association between center case volume and FTR, adjusting for patient demographics, race, insurance, comorbidities, procedure type, and year.<br /><b>Results</b><br />A total of 43,641 patients were included across 17 centers during the study period. Of these, 5315 (12.2%) developed an FTR complication, and 735 (13.8% of those who developed an FTR complication) experienced FTR. Median annual case volume was 226, with 25th and 75th-percentile cutoffs of 136 and 284 cases, respectively. Increasing center-level case volume was associated with significantly higher center-level major complication rates, but lower mortality and FTR rates (all p-values < 0.01). Observed to expected FTR was significantly associated with case volume (p = 0.040). Increasing case volume was independently associated with decreasing FTR rate in the final multivariable model (OR 0.87 per quartile, CI 0.80 - 0.95, p = 0.001).<br /><b>Conclusions</b><br />Increasing center case volume is significantly associated with improved failure to rescue rates. Assessment of low volume centers\' FTR performance represents an opportunity for quality improvement.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Thorac Cardiovasc Surg: 19 May 2023; epub ahead of print</small></div>

<div><h4>Effect of the UNOS policy change on rates of rejection, infection and hospital readmission following heart transplantation.</h4><i>Vaidya AS, Lee ES, Kawaguchi ES, DePasquale EC, ... Lee R, Wolfson AM</i><br /><b>Background</b><br />The 2018 adult heart allocation policy sought to improve waitlist risk stratification, reduce waitlist mortality and increase organ access. This system prioritized patients at greatest risk for waitlist mortality, especially individuals requiring temporary mechanical circulatory support (tMCS). Post-transplant complications are significantly higher in patients on tMCS before transplantation, and early post-transplant complications impact long-term mortality. We sought to determine if policy change affected early post-transplant complication rates of rejection, infection and hospitalization.<br /><b>Methods</b><br />We included all adult, heart-only, single-organ heart transplant recipients from the UNOS registry with pre-policy (PRE) individuals transplanted between 11/1/2016 to 10/31/2017 and post-policy (POST) between 11/1/2018 to 10/31/2019. We used a multivariable logistic regression analysis to assess the effect of policy change on post-transplant rejection, infection, and hospitalization. Two COVID-19 eras (2019-2020, 2020-2021) were included in our analysis.<br /><b>Results</b><br />The majority of baseline characteristics were comparable between PRE and POST era recipients. The odds of treated rejection (p=0.8), hospitalization (p=0.69), and hospitalization due to rejection (p=0.76) and infection (p=0.66) were similar between PRE and POST eras; there was a trend towards reduced odds of rejection (p=0.08). In both COVID eras, there was a clear reduction in rejection and treated rejection with no effect on hospitalization for rejection or infection. Odds of all-cause hospitalization was increased in both COVID eras.<br /><b>Conclusion</b><br />The UNOS policy change improves access to heart transplantation for higher acuity patients without increasing early post-transplant rates of treated rejection or hospitalization for rejection or infection, factors which portend risk for long-term post-transplant mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 19 May 2023; epub ahead of print</small></div>

<div><h4>Machine Learning for Clustering and Post-closure Outcome of Adult CHD-PAH Patients with Borderline Hemodynamics.</h4><i>Luo D, Zheng X, Yang Z, Li H, Fei H, Zhang C</i><br /><b>Background</b><br />Patients with uncorrected isolated simple shunts associated pulmonary arterial hypertension (PAH) had increased mortality. Treatment strategies for borderline hemodynamics remain controversial. This study aims to investigate pre-closure characteristics and its association with post-closure outcome in this group of patients.<br /><b>Methods</b><br />Adults with uncorrected isolated simple shunts associated PAH were included. Peak tricuspid regurgitation velocity <2.8m/s with normalized cardiac structures was defined as the favorable study outcome. We applied unsupervised and supervised machine learning for clustering analysis and model constructions.<br /><b>Results</b><br />Finally, 246 patients were included. During a median follow-up of 414 days, 58.49% (62/106) of patients with pre-tricuspid shunts achieved favorable outcome while 32.22% (46/127) of patients with post-tricuspid shunts. In unsupervised learning, two clusters were identified in both types of shunts. Generally, the oxygen saturation, pulmonary blood flow, cardiac index, dimensions of the right and left atrium, were the major features that characterized the identified clusters. Specifically, mean right atrial pressure, right ventricular dimension and right ventricular outflow tract helped differentiate clusters in pre-tricuspid shunts while age, aorta dimension and systemic vascular resistance helped differentiate clusters for post-tricuspid shunts. Notably, cluster 1 had better post-closure outcome than cluster 2 (70.83% vs. 32.55%, P<0.001 for pre-tricuspid and 48.10% vs. 16.67%, P<0.001 for post-tricuspid). However, models constructed from supervised learning methods did not achieve good accuracy for predicting the post-closure outcome.<br /><b>Conclusions</b><br />There were two main clusters in patients with borderline hemodynamics, in which one cluster had better post-closure outcome than the other.<br /><b>Data availability statement</b><br />The datasets and analyzed codes are available upon reasonable request from the corresponding author.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 19 May 2023; epub ahead of print</small></div>

<div><h4>Thoracoabdominal Normothermic Regional Perfusion in Donation after Circulatory Death Does Not Restore Brain Blood Flow.</h4><i>Frontera JA, Lewis A, James L, Melmed K, ... Smith DE, Moazami N</i><br /><AbstractText>Use of thoraco-abdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 19 May 2023; epub ahead of print</small></div>

<div><h4>Duration of Heart Failure with Preserved Ejection Fraction and Outcomes with Sacubitril/Valsartan: Insights from the PARAGON-HF Trial.</h4><i>Ostrominski JW, Claggett BL, Packer M, Pfeffer MA, ... Solomon SD, Vaduganathan M</i><br /><b>Aims</b><br />In this post hoc analysis of the PARAGON-HF trial, we evaluated clinical outcomes and response to sacubitril/valsartan by duration of heart failure (HF) with left ventricular ejection fraction ≥45% from initial diagnosis.<br /><b>Methods and results</b><br />The primary outcome was a composite of total HF hospitalizations and cardiovascular death, analyzed using a semiparametric proportional rates method, stratified by geographic region. Among 4,784 (99.7%) randomized PARAGON-HF participants for whom baseline HF duration was captured, 1,359 (28%) had a HF duration of <6 months, 1,295 (27%) 6 months-2 years, and 2,130 (45%) >2 years. Longer HF duration was associated with higher comorbidity burden, worse health status, and a lower rate of prior HF hospitalization. Over a median follow-up of 35 months, longer HF duration was associated with a higher risk of first and recurrent primary events (per 100 patient-years): <6 months, 12.0 (95% CI, 10.4-14.0); 6 months-2 years, 12.2 (10.6-14.2); >2 years, 15.8 (14.2-17.5). Relative treatment effects of sacubitril/valsartan vs. valsartan were consistent irrespective of baseline HF duration on the primary endpoint (P<sub>interaction</sub>=0.112). Clinically meaningful (≥5 point) improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score were also similarly observed irrespective of HF duration; P<sub>interaction</sub>=0.112). Adverse events were similar between treatment arms across HF duration categories.<br /><b>Conclusions</b><br />In PARAGON-HF, longer HF duration was independently predictive of adverse HF outcomes. Treatment effects of sacubitril/valsartan were consistent irrespective of baseline HF duration, suggesting that even ambulatory patients with longstanding HFpEF and predominantly mild symptoms stand to benefit from treatment optimization.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 19 May 2023; epub ahead of print</small></div>

<div><h4>Remote haemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure (MONITOR-HF): a randomised clinical trial.</h4><i>Brugts JJ, Radhoe SP, Clephas PRD, Aydin D, ... de Boer RA, MONITOR-HF investigators</i><br /><b>Background</b><br />The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system.<br /><b>Methods</b><br />MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform.<br /><b>Findings</b><br />Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61-75) and median ejection fraction was 30% (23-40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51-12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and -0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01-2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26-0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively.<br /><b>Interpretation</b><br />Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring.<br /><b>Funding</b><br />The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Lancet: 19 May 2023; epub ahead of print</small></div>

<div><h4>Heart failure pharmacological treatments and outcomes in heart failure with mildly reduced ejection fraction.</h4><i>Stolfo D, Lund LH, Sinagra G, Lindberg F, ... Rosano G, Savarese G</i><br /><b>Background</b><br />Guideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials.<br /><b>Objectives</b><br />We investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF.<br /><b>Methods</b><br />Patients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH) and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint.<br /><b>Results</b><br />Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH (HR = 0.90, 95%CI:0.83-0.98 and HR = 0.82, 95%CI:0.74-0.90, respectively) and of all-cause mortality (HR = 0.75, 95%CI:0.69-0.81 and HR = 0.79, 95%CI:0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome.<br /><b>Conclusions</b><br />RASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm in the real world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 18 May 2023; epub ahead of print</small></div>

<div><h4>Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study.</h4><i>Yoo TK, Han KD, Rhee EJ, Lee WY</i><br /><b>Background</b><br />Few studies have assessed the correlation between coexisting mental disorders in participants with diabetes mellitus (DM) and the risk of heart failure (HF). Herein, we conducted a cohort study to determine the association between the accumulation of mental disorders in participants with DM and the risk of HF.<br /><b>Methods</b><br />The Korean National Health Insurance Service records were assessed. 2,447,386 adults with DM who underwent health screening between 2009 and 2012 were analyzed. Participants with major depressive disorder, bipolar disorder, schizophrenia, insomnia, or anxiety disorders were included. In addition, participants were categorized based on the number of coexisting mental disorders. Each participant was followed until December 2018 or until the onset of HF. Cox proportional hazard modelling with confounding factors adjustment was conducted. In addition, a competing risk analysis was conducted. Subgroup analysis assessed the impact of clinical variables on the association between the accumulation of mental disorders and the risk of HF.<br /><b>Results</b><br />The median follow-up duration was 7.09 years. The accumulation of mental disorders was associated with a risk of HF (zero mental disorder (0), reference; 1 mental disorder, adjusted hazard ratio (aHR): 1.222, 95% confidence intervals (CI): 1.207-1.237; 2 mental disorders, aHR: 1.426, CI: 1.403-1.448; ≥3 mental disorders, aHR: 1.667, CI: 1.632-1.70. In the subgroup analysis, the strength of association was the strongest in the younger age group (< 40 years, 1 mental disorder, aHR 1.301, CI 1.143-1.481; ≥2 mental disorders, aHR 2.683, CI 2.257-3.190; 40-64 years, 1 mental disorder, aHR 1.289, CI 1.265-1.314; ≥2 mental disorders, aHR 1.762, CI 1.724-1.801; ≥65 years, 1 mental disorder, aHR 1.164, CI 1.145-1.183; ≥2 mental disorders, aHR 1.353, CI 1.330-1.377; P<sub>inter</sub><0.001). In addition, income, BMI, hypertension, chronic kidney disease, history of cardiovascular disease, insulin use, and duration of DM showed significant interactions.<br /><b>Conclusions</b><br />Comorbid mental disorders in participants with DM are associated with an increased risk of HF. In addition, the association was stronger in a younger age group. Participants with DM and mental disorders should be monitored with increased frequency for signs of HF; for which they have a higher risk than the general population.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 18 May 2023; 22:115</small></div>

<div><h4>Medical Costs of Chronic Kidney Disease and Type 2 Diabetes Among Newly Diagnosed Heart Failure Patients With Reduced, Mildly Reduced, and Preserved Ejection Fraction.</h4><i>Nichols GA, Qiao Q, Linden S, Kraus BJ</i><br /><AbstractText>The economic burden of heart failure (HF) is enormous, but studies of HF costs typically consider the disease to be a single entity. We sought to distinguish the medical costs for patients with HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). We identified 16,516 adult patients with an incident HF diagnosis and an echocardiogram from 2005 to 2017 in the electronic medical record of Kaiser Permanente Northwest. Using the echocardiogram nearest to the first diagnosis date, we classified patients with HFrEF (ejection fraction [EF] ≤40%), HFmrEF (EF 41% to 49%), or HFpEF (EF ≥50%). We calculated annualized inpatient, outpatient, emergency, pharmaceutical medical utilization and costs and total costs in $2,020, adjusted for age and gender using generalized linear models, with further analysis of the effects of co-morbid chronic kidney disease (CKD) and type 2 diabetes (T2D). For all HF types, 1 in 5 patients were affected by both CKD and T2D, and costs were significantly higher when both co-morbidities were present. Total per-person costs were significantly higher for HFpEF ($33,740, 95% confidence interval $32,944 to $34,536) than HFrEF ($27,669, $25,649 to $29,689) or HFmrEF ($29,484, $27,166 to $31,800), driven by in- and outpatient visits. Across HF types, visits approximately doubled with the presence of both co-morbidities. Due to greater prevalence, HFpEF accounted for the majority of total and resource-specific treatment costs of HF, regardless of the presence of CKD and/or T2D. In summary, the economic burden was greater per HFpEF patient and was further amplified by co-morbid CKD and T2D. HFpEF accounted for the large majority of total HF costs, underscoring the need to implement effective treatments.</AbstractText><br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 18 May 2023; 198:72-78</small></div>

<div><h4>Voice-Assisted Artificial Intelligence Enabled Screening for SARS-CoV-2 Exposure in Cardiovascular Clinics: Primary results of the VOICE-COVID-19-II Randomized Trial.</h4><i>Sharma A, Marques P, Zhang G, Oulousian E, ... Razaghizad A, Avram R</i><br /><b>Background</b><br />Voice-assisted artificial intelligence (AI)-based systems may streamline clinical care among patients with heart failure (HF) and caregivers; however, randomized clinical trials are needed. We evaluated the potential for Amazon Alexa® (Alexa), a voice-assisted AI-based system, to conduct screening for SARS-CoV2 in a HF clinic.<br /><b>Methods and results</b><br />We enrolled 52 participants (patients and caregivers) from a HF clinic, who were randomly assigned with a subsequent cross-over to receive a SARS-CoV-2 screening questionnaire via Alexa or healthcare personnel. Primary outcome was overall response concordance, as measured by the percentage of agreement and unweighted kappa scores between groups. A post-screening survey evaluated comfort with using the AI-based device. In total, 36 (69%) participants were male, the median age was 51 (34-65) years and 36 (69%) were English-speaking. Twenty-one (40%) participants were HF patients. For the primary outcome, there were no statistical differences between groups: Alexa - Research coordinator group 96.9% agreement and unweighted kappa score of 0.92 (CI 0.84-1.00) versus Research coordinator - Alexa group 98.5% agreement and unweighted kappa score of 0.95 (CI 0.88-1.00) (p-value for all comparisons > 0.05). Overall, 87% of participants rated their screening experience as good or outstanding.<br /><b>Conclusion</b><br />Alexa demonstrated comparable performance to a healthcare professional for SARS-CoV2 screening in a group of HF patients and caregivers and may represent an attractive approach to symptoms screening in this population. Future studies evaluating such technologies for other uses among patients with HF and caregivers are warranted. NCT04508972.<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 18 May 2023; epub ahead of print</small></div>

<div><h4>Prognostic value of right ventricular longitudinal strain in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair.</h4><i>Lupi L, Italia L, Pagnesi M, Pancaldi E, ... Metra M, Adamo M</i><br /><b>Aims</b><br />To evaluate the prognostic impact of pre-procedural right ventricular longitudinal strain (RVLS) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge repair (TEER) in comparison with conventional echocardiographic parameters of RV function.<br /><b>Methods and results</b><br />This is a retrospective study including 142 patients with SMR undergoing TEER at two Italian centres. At 1-year follow-up 45 patients reached the composite endpoint of all-cause death or heart failure hospitalization. The best cut-off value of RV free-wall longitudinal strain (RVFWLS) to predict outcome was -18% [sensitivity 72%, specificity of 71%, area under curve (AUC) 0.78, P < 0.001], whereas the best cut-off value of RV global longitudinal strain (RVGLS) was -15% (sensitivity 56%, specificity 76%, AUC 0.69, P < 0.001). Prognostic performance was suboptimal for tricuspid annular plane systolic excursion, Doppler tissue imaging-derived tricuspid lateral annular systolic velocity and fractional area change (FAC). Cumulative survival free from events was lower in patients with RVFWLS ≥ -18% vs. RVFWLS < -18% (44.0% vs. 85.4%; < 0.001) as well as in patients with RVGLS ≥ -15% vs. RVGLS < -15% (54.9% vs. 81.7%; P < 0.001). At multivariable analysis FAC, RVGLS and RVFWLS were independent predictors of events. The identified cut-off of RVFWLS and RVGLS both resulted independently associated with outcomes.<br /><b>Conclusion</b><br />RVLS is a useful and reliable tool to identify patients with SMR undergoing TEER at high risk of mortality and HF hospitalization, on top of other clinical and echocardiographic parameters, with RVFWLS offering the best prognostic performance.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 17 May 2023; epub ahead of print</small></div>

<div><h4>Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure With Pulmonary Hypertension.</h4><i>Jani V, Aslam MI, Fenwick AJ, Ma W, ... Kass DA, Hsu S</i><br /><b>Background</b><br />Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in patients with heart failure with reduced ejection fraction and pulmonary hypertension (HFrEF-PH). However, such dysfunction often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction. We thus sought to characterize RV myocyte contractile depression in HFrEF-PH, identify those components reflected by clinical RV indices, and uncover underlying biophysical mechanisms.<br /><b>Methods</b><br />Resting, calcium-, and load-dependent mechanics were prospectively studied in permeabilized RV cardiomyocytes isolated from explanted hearts from 23 patients with HFrEF-PH undergoing cardiac transplantation and 9 organ donor controls.<br /><b>Results</b><br />Unsupervised machine learning using myocyte mechanical data with the highest variance yielded 2 HFrEF-PH subgroups that in turn mapped to patients with decompensated or compensated clinical RV function. This correspondence was driven by reduced calcium-activated isometric tension in decompensated clinical RV function, whereas surprisingly, many other major myocyte contractile measures including peak power and myocyte active stiffness were similarly depressed in both groups. Similar results were obtained when subgroups were first defined by clinical indices, and then myocyte mechanical properties in each group compared. To test the role of thick filament defects, myofibrillar structure was assessed by x-ray diffraction of muscle fibers. This revealed more myosin heads associated with the thick filament backbone in decompensated clinical RV function, but not compensated clinical RV function, as compared with controls. This corresponded to reduced myosin ATP turnover in decompensated clinical RV function myocytes, indicating less myosin in a crossbridge-ready disordered-relaxed (DRX) state. Altering DRX proportion (%DRX) affected peak calcium-activated tension in the patient groups differently, depending on their basal %DRX, highlighting potential roles for precision-guided therapeutics. Last, increasing myocyte preload (sarcomere length) increased %DRX 1.5-fold in controls but only 1.2-fold in both HFrEF-PH groups, revealing a novel mechanism for reduced myocyte active stiffness and by extension Frank-Starling reserve in human heart failure.<br /><b>Conclusions</b><br />Although there are many RV myocyte contractile deficits in HFrEF-PH, commonly used clinical indices only detect reduced isometric calcium-stimulated force, which is related to deficits in basal and recruitable %DRX myosin. Our results support use of therapies to increase %DRX and enhance length-dependent recruitment of DRX myosin heads in such patients.<br /><br /><br /><br /><small>Circulation: 17 May 2023; epub ahead of print</small></div>

<div><h4>Causal relationships between the gut microbiome, blood lipids, and heart failure: a Mendelian randomization analysis.</h4><i>Dai H, Hou T, Wang Q, Hou Y, ... Bi Y, Xu M</i><br /><b>Background</b><br />Studies have linked gut microbiome and heart failure (HF). However, their causal relationships and potential mediating factors have not been well defined.<br /><b>Aims</b><br />To investigate the causal relationships between the gut microbiome and HF and the mediating effect of potential blood lipids by using genetics.<br /><b>Method</b><br />We performed a bidirectional and mediation Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of gut microbial taxa (Dutch Microbiome Project, n = 7,738), blood lipids (UK Biobank, n = 115,078), and a meta-analysis of HF (115,150 cases and 1,550,331 controls). We applied the inverse-variance weighted estimation method as the primary method, with several other estimators as complementary methods. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal lipids.<br /><b>Results</b><br />Six microbial taxa are suggestively associated with HF causally. The most significant taxon was the species Bacteroides dorei (odds ratio = 1.059, 95% confidence interval [CI] = 1.022 - 1.097, P value = 0.0017). The MR-BMA analysis showed that apolipoprotein B (ApoB) was the most likely causal lipid for HF (the marginal inclusion probability = 0.717, P value = 0.005). The mediation MR analysis showed that ApoB mediated the causal effects of species Bacteroides dorei on HF (proportion mediated = 10.1%, 95% CI = 0.2% - 21.6%, P value = 0.031).<br /><b>Conclusion</b><br />The study suggested a causal relationship between specific gut microbial taxa and HF and that ApoB might mediate this relationship as the primary lipid determinant of HF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur J Prev Cardiol: 17 May 2023; epub ahead of print</small></div>

<div><h4>Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories.</h4><i>Butler J, Packer M, Siddiqi TJ, Böhm M, ... Anker SD, Zannad F</i><br /><b>Background</b><br />Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction.<br /><b>Objectives</b><br />The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively).<br /><b>Methods</b><br />A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively.<br /><b>Results</b><br />In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very-high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved.<br /><b>Conclusions</b><br />The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 May 2023; 81:1902-1914</small></div>

<div><h4>Clinical characteristics of HFrEF patients with rare pathogenic variants in DCM-associated genes: a subgroup analysis of the PARADIGM-HF trial.</h4><i>Barat A, Chen CW, Patel-Murray N, McMurray JJV, ... Yates D, Gimpelewicz C</i><br /><b>Aims</b><br />To evaluate the prevalence of pathogenic variants in genes associated with dilated cardiomyopathy (DCM) in a clinical trial population with heart failure and reduced ejection fraction (HFrEF) and describe the baseline characteristics by variant carrier status.<br /><b>Methods and results</b><br />This was a post hoc analysis of the Phase 3 PARADIGM-HF trial. Forty-four genes, divided into three tiers, based on definitive, moderate or limited evidence of association with DCM, were assessed for rare predicted loss-of-function (pLoF) variants, which were prioritised using ClinVar annotations, measures of gene transcriptional output and evolutionary constraint, and pLoF confidence predictions. Prevalence was reported for pLoF variant carriers based on DCM-associated gene tiers. Clinical features were compared between carriers and non-carriers. Of the 1412 HFrEF participants with whole-exome sequence data, 68 (4.8%) had at least one pLoF variant in the 8 tier-1 genes (definitive/strong association with DCM), with Titin being most commonly affected. The prevalence increased to 7.5% when considering all 44 genes. Among patients with idiopathic aetiology, 10.0% (23/229) had tier-1 variants only and 12.6% (29/229) had tier-1, -2 or -3 variants. Compared to non-carriers, tier-1 carriers were younger (4 years; adjusted p-value [p<sub>adj</sub> ]=4×10<sup>-3</sup> ), leaner (27.8 kg/m<sup>2</sup> vs. 29.4 kg/m<sup>2</sup> ; p<sub>adj</sub> =3.2x10<sup>-3</sup> ), had lower EF (27.3% vs. 29.8%; p<sub>adj</sub> =5.8x10<sup>-3</sup> ), and less likely to have ischaemic aetiology (37.3% vs 67.4%; p<sub>adj</sub> =4×10<sup>-4</sup> ).<br /><b>Conclusion</b><br />Deleterious pLoF variants in genes with definitive/strong association to DCM were identified in ~5% of HFrEF patients from a PARADIGM-HF trial subset, who were younger, had lower EF and were less likely to have had an ischaemic aetiology. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 May 2023; epub ahead of print</small></div>

<div><h4>Positive Airway Pressure Adherence and Health Care Resource Utilization in Patients With Obstructive Sleep Apnea and Heart Failure With Reduced Ejection Fraction.</h4><i>Malhotra A, Cole KV, Malik AS, Pépin JL, ... Somers VK, medXcloud group *</i><br /><AbstractText><br /><b>Background:</b><br/>Obstructive sleep apnea (OSA) is a common comorbidity in patients with heart failure, although current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in patients with heart failure. This study assessed the impact of adherence to PAP therapy on health care resource utilization in patients with OSA and heart failure with reduced ejection fraction. Methods and Results Administrative insurance claims data linked with objective PAP therapy use data from patients with OSA and heart failure with reduced ejection fraction were used to determine associations between PAP adherence and a composite outcome of hospitalizations and emergency room visits. One-year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 3182 patients (69.9% male, mean age 59.7 years); 39% were considered adherent to PAP therapy (29% intermediate adherent, 31% nonadherent). One year after PAP initiation, adherent patients had fewer composite visits than matched nonadherent patients, driven by a 24% reduction in emergency room visits for adherent patients. Composite visit costs were lower in adherent versus nonadherent patients ($3500 versus $5879, <i>P</i>=0.031), although total health care costs were not statistically different ($13 028 versus $14 729, <i>P</i>=0.889). <br /><b>Conclusions:</b><br/>PAP therapy adherence in patients with OSA with heart failure with reduced ejection fraction was associated with a reduction in health care resource utilization. This suggests that greater emphasis should be placed on diagnosing and effectively treating OSA with PAP in patients with heart failure with reduced ejection fraction.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028732</small></div>

<div><h4>Racial Differences in Quality of Life in Patients With Heart Failure Treated With Sodium-Glucose Cotransporter 2 Inhibitors: A Patient-Level Meta-Analysis of the CHIEF-HF, DEFINE-HF, and PRESERVED-HF Trials.</h4><i>Gupta K, Spertus JA, Birmingham M, Gosch KL, ... Kosiborod M, Lanfear DE</i><br /><b>Background</b><br />Health status outcomes, including symptoms, function, and quality of life, are worse for Black compared with White patients with heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular mortality and improve health status in patients with heart failure, but whether the health status benefit of SGLT2is is similar across races is not established. The objective of this study was to compare the treatment effect of SGLT2is (versus placebo) on health status for Black compared with White patients with heart failure.<br /><b>Methods</b><br />We combined patient-level data from 3 randomized clinical trials of SGLT2is: DEFINE-HF (Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure; n=263), PRESERVED-HF (Dapagliflozin in Preserved Ejection Fraction Heart Failure; n=324), and CHIEF-HF (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure; n=448). These 3 United States-based trials enrolled a substantial proportion of Black patients, and each used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to measure health status at baseline and after 12 weeks of treatment. Among 1035 total participants, selecting self-identified Black and White patients with complete information yielded a final analytic cohort of 935 patients. The primary endpoint was KCCQ Clinical Summary score. Twelve-week change in KCCQ with SGLT2is versus placebo was compared between Black and White patients by testing the interaction between race and treatment using multivariable linear regression models adjusted for trial, baseline KCCQ (as a restricted cubic spline), race, and treatment. The data that support the findings of this study are available from the corresponding author upon reasonable request.<br /><b>Results</b><br />Among 935 participants, 236 (25%) self-identified as Black, and 469 (50.2%) were treated with an SGLT2i. Treatment with an SGLT2i, compared with placebo, resulted in KCCQ Clinical Summary score improvements at 12 weeks of +4.0 points (95% CI, 1.7-6.3; <i>P</i>=0.0007) in White patients and +4.7 points (95% CI, 0.7-8.7; <i>P</i>=0.02) in Black patients, with no significant interaction by race and treatment (<i>P</i>=0.76). Other KCCQ scales showed similar results.<br /><b>Conclusions</b><br />Treatment with an SGLT2i resulted in consistent and significant improvements in health status for both Black and White patients with heart failure.<br /><br /><br /><br /><small>Circulation: 16 May 2023; epub ahead of print</small></div>

<div><h4>Global Variations in Heart Failure Etiology, Management, and Outcomes.</h4><i>G-CHF Investigators, Joseph P, Roy A, Lonn E, ... Probstfield J, Yusuf S</i><br /><b>Importance</b><br />Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries.<br /><b>Objective</b><br />To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development.<br /><b>Design, setting, and participants</b><br />Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years.<br /><b>Main outcomes and measures</b><br />HF cause, HF medication use, hospitalization, and death.<br /><b>Results</b><br />Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a β-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.<br /><br /><br /><br /><small>JAMA: 16 May 2023; 329:1650-1661</small></div>

<div><h4>Sex-specific analysis of the rapid up-titration of guideline-directed medical therapies after a hospitalisation for acute heart failure: insights from the STRONG-HF trial.</h4><i>Čerlinskaitė-Bajorė K, Lam CSP, Sliwa K, Adamo M, ... Cotter G, Čelutkienė J</i><br /><b>Aims</b><br />The aim of this study was to evaluate efficacy and safety of rapid up-titration of guideline directed medical therapies in men and women hospitalized for acute heart failure (AHF).<br /><b>Methods and results</b><br />In STRONG-HF AHF patients were randomised just prior to discharge to either usual care (UC) or a high-intensity care (HIC) strategy of guideline-directed medical therapies (GDMT) up-titration. In these analyses, we compare the implementation, efficacy, and safety of the HIC strategy between men and women. In the randomised AHF population, 416/1078 (39%) were women. By day 90, a higher proportion of both sexes in the HIC group had been up-titrated to full doses of GDMT compared to UC. Overall, there were no differences in the primary endpoint between the sexes. The primary endpoint, 180-day HF readmission or death, occurred in 15.8% HIC women vs 23.5% women in the UC group (adjusted HR 0.67 [95% CI 0.40-1.13]) and in 14.9% HIC men vs 23.5% UC men (adjusted HR 0.57 [95% CI 0.38-0.88]), adjusted interaction p = 0.65. There was no significant treatment-by-sex interaction in quality-of-life improvement or in adverse events, including serious or fatal adverse events.<br /><b>Conclusion</b><br />The results of the current analyses suggest that a rapid up-titration of GDMT immediately after an AHF hospitalisation can and should be implemented similarly in men and women, as it results in reduction of 180-day all-cause death or HF readmission, quality-of-life improvement in both men and women with a similar safety profile.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 May 2023; epub ahead of print</small></div>

<div><h4>Prevalence, Characteristics and Cardiovascular and Non-cardiovascular Outcomes in Patients with Heart Failure with Supra-normal Ejection Fraction; Insight from the JROADHF Study.</h4><i>Horiuchi Y, Asami M, Ide T, Yahagi K, ... Tsutsui H, Tanabe K</i><br /><b>Aims</b><br />We aimed to investigate the characteristics and prognosis of patients with heart failure with supra-normal ejection fraction (HFsnEF) compared to HF with normal EF (HFnEF).<br /><b>Methods and results</b><br />Among 11,573 patients enrolled in the nationwide registry of hospitalized patients with HF in Japan, 1,943 patients (16.8%) were classified as HFsnEF (left ventricular EF [LVEF] > 65%), 3,277 (28.3%) as HFnEF (50% ≤ LVEF ≤ 65%), 2,024 (17.5%) as HF with mildly reduced EF (40% ≤ EF < 50%) and 4,329 (37.4%) as HF with reduced EF (LVEF < 40%). Patients with HFsnEF were older, more likely to be women, had lower natriuretic peptide values, and had smaller left ventricles than those with HFnEF. The primary endpoint, the composite of cardiovascular death or HF readmission, did not differ between HFsnEF (802/1943, 41.3%) and HFnEF (1413/3277, 43.1%) during a median follow-up period of 870 days (hazard ratio [HR] 0.96 [0.88-1.05], p = 0.346). The incidence of secondary outcomes, including all-cause, cardiovascular, and non-cardiovascular deaths and HF readmission, did not differ between HFsnEF and HFnEF. In the multivariable Cox regression analysis, HFsnEF compared to HFnEF was associated with a lower adjusted HR for HF readmission but not with the primary and other secondary endpoints. HFsnEF was associated with a higher HR for the composite endpoint and all-cause death in women, and a higher HR for all-cause death in patients with renal dysfunction.<br /><b>Conclusions</b><br />HFsnEF is a common and distinctive phenotype, and has different characteristics and prognoses from HFnEF. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 May 2023; epub ahead of print</small></div>

<div><h4>Incremental prognostic value of biomarkers in PARADIGM-HF.</h4><i>McDowell K, Campbell R, Simpson J, Cunningham JW, ... Packer M, McMurray JJV</i><br /><b>Background</b><br />It is uncertain how much candidate biomarkers improve risk prediction when added to comprehensive models including routinely collected clinical and laboratory variables in heart failure.<br /><b>Methods</b><br />Aldosterone, cystatin C, high sensitivity-troponin T (hs-TnT), galectin-3, growth differentiation factor-15 (GDF-15), kidney injury molecule-1 (KIM-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), soluble suppression of tumorigenicity-2 (ST2), tissue inhibitor of metalloproteinase-1 (TIMP-1) and urinary albumin to creatinine ratio (UACR) were measured in 1559 of PARADIGM-HF participants.We tested whether these biomarkers, individually or collectively, improved the performance of the PREDICT-HF prognostic model, which includes clinical, routine laboratory, and natriuretic peptide data, for the primary endpoint and cardiovascular and all-cause mortality.<br /><b>Results</b><br />The mean age of participants was 67.3 ± 9.9 years, 1254 (80.4%) were men and 1103 (71%) were NYHA class II. During a mean follow-up of 30.7 months, 300 patients experienced the primary outcome and 197 died. Added individually, only 4 biomarkers were independently associated with all outcomes: hs-TnT, GDF-15, cystatin C and TIMP-1. When all biomarkers were added simultaneously to the PREDICT-HF models, only hs-TnT remained an independent predictor of all three endpoints. GDF-15 also remained predictive of the primary endpoint; TIMP-1 was the only other predictor of both cardiovascular and all-cause mortality. Individually or in combination, these biomarkers did not lead to statistically significant improvements in discrimination or reclassification.<br /><b>Conclusions</b><br />None of the biomarkers studied individually or collectively led to a meaningful improvement in the prediction of outcomes over what is provided by clinical, routine laboratory, and natriuretic peptide variables. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 May 2023; epub ahead of print</small></div>

<div><h4>Identifying distinct clinical clusters in heart failure with mildly reduced ejection fraction.</h4><i>Meijs C, Brugts JJ, Lund LH, Linssen GCM, ... Savarese G, Uijl A</i><br /><b>Introduction</b><br />Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41-49% EF) is only recently recognized as a distinct entity. Cluster analysis can characterize heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis.<br /><b>Methods and results</b><br />Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registry-based dataset CHECK-HF (n = 1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7-1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2-1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2-3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5-3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2-3.6]). The cluster model was robust between both datasets.<br /><b>Conclusion</b><br />We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 May 2023; epub ahead of print</small></div>

<div><h4>Natural History of Chronic Thromboembolic Pulmonary Disease with no or mild Pulmonary Hypertension.</h4><i>Ashwin Reddy S, Swietlik EM, Robertson L, Michael A, ... Toshner MR, Pepke-Zaba J</i><br /><b>Introduction</b><br />We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease (CTEPD) patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension (PH).<br /><b>Method</b><br />All patients diagnosed with CTEPD between January 2015 and December 2019 were dichotomised according to initial mPAP: ≤20mmHg (\'normal\') vs. 21-24mmHg (\'mildly-elevated\'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy (PEA) or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period.<br /><b>Results</b><br />113 patients were included; 57 had mPAP ≤20mmHg and 56 had mPAP 21-24mmHg. Normal mPAP patients had lower pulmonary vascular resistance (PVR) (1.6 vs 2.5WU, p < 0.01) and right ventricular end-diastolic pressure (RVEDP) (5.9 vs 7.8mmHg, p<0.01) at presentation. At 3 years no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. 8 had undergone PEA. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases.<br /><b>Conclusion</b><br />CTEPD patients with mild PH have statistically higher RVEDP and PVR than those with mPAP ≤20mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings.<br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 16 May 2023; epub ahead of print</small></div>

<div><h4>Right Ventricular Function and Coupling to Pulmonary Circulation in Heart Failure with Preserved Ejection Fraction: The PARAGON-HF Trial.</h4><i>Inciardi RM, Abanda M, Shah A, Cikes M, ... McMurray JJV, Solomon SD</i><br /><b>Background</b><br />Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction(HFpEF).<br /><b>Objectives</b><br />To assess the clinical implications of RV function, the association with N-terminal pro-B-type-natriuretic-peptide (NT-proBNP) and the risk for adverse events among HFpEF patients.<br /><b>Methods</b><br />We analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (RVFWLS/PASP ratio) in 528 patients (mean age 74±8 years, 56%female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline NT-proBNP and with total HF hospitalizations and cardiovascular (CV) death were assessed, after accounting for confounders.<br /><b>Results</b><br />Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion (TAPSE) and RV fractional area change, more than half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating NT-proBNP. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and CV deaths. Both absolute RVFWLS (hazard ratio(HR):1.39; 95%confidence interval(95%CI):1.05-1.83;p-value=0.018) and RVFWLS/PASP ratio (HR:1.43;95%CI:1.13-1.80;p-value=0.002) were significantly associated with the composite outcome. Treatment effect of Sacubitril/Valsartan was not modified by measures of RV function.<br /><b>Conclusion</b><br />Worsening RV function and its ratio to pulmonary pressure, is common and significantly associated with an increased risk of HF hospitalizations and CV death in patients with HFpEF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 15 May 2023; epub ahead of print</small></div>

<div><h4>Comprehensive Characterization of Non-Cardiac Comorbidities in Acute Heart Failure- an analysis of ESC-HFA EORP Heart Failure Long-Term Registry.</h4><i>Chioncel O, Benson L, Crespo-Leiro MG, Anker SD, ... Maggioni AP, Lund LH</i><br /><b>Purpose</b><br />To evaluate the prevalence and associations of non-cardiac comorbidities (NCC) with in-hospital and post-discharge outcomes in acute heart failure (AHF) across the ejection fraction (EF) spectrum.<br /><b>Methods</b><br />9326 AHF patients from ESC-HFA-EORP-HF-Long-Term-Registry had complete information for the following 12 NCCs: anemia, chronic obstructive pulmonary disease (COPD), diabetes, depression, hepatic dysfunction, renal dysfunction, malignancy, Parkinson disease, peripheral vascular disease (PVD), rheumatoid arthritis, sleep apnoea, stroke/TIA(transient ischemic attack). Patients were classified by number of NCCs (0, 1, 2, 3, and ≥4).<br /><b>Results</b><br />Of AHF patients, 20.5% had no NCC, 28.5% had 1 NCC, 23.1% had 2 NCC, 15.4% had 3 NCC and 12.5% had ≥4 NCC. In-hospital and post-discharge mortality increased with number of NCCs from 3.0% and 18.5% for 1 NCC to 12.5% and 36% for ≥4 NCCs.Anemia, COPD, PVD, sleep apnoea, rheumatoid arthritis, stroke/TIA, Parkinson and depression were more prevalent in HFpEF. The hazard ratio (95% confidence interval) for post-discharge death for each NCC was for anemia 1.6 (1.4-1.8), diabetes 1.2 (1.1-1.4), kidney dysfunction 1.7 (1.5-1.9), COPD 1.4 (1.2-1.5), PVD 1.2 (1.1-1.4), stroke/TIA 1.3 (1.1-1.5), depression 1.2 (1.0-1.5), haepatic dysfunction 2.1 (1.8-2.5), malignancy 1.5 (1.2-1.8), sleep apnoea 1.2 (0.9-1.7), rheumatoid arthritis 1.5 (1.1-2.1) and Parkinson 1.4 (0.9-2.1). Anemia, kidney dysfunction, COPD and diabetes were associated with post-discharge mortality in all EF categories, PVD, stroke/TIA and depression only in HFrEF and sleep apnoea and malignancy only in HFpEF.<br /><b>Conclusion</b><br />Multiple NCCs conferred poor in-hospital and post-discharge outcomes. EF categories had different prevalence and risk profile associated with individual NCCs.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur J Prev Cardiol: 13 May 2023; epub ahead of print</small></div>

<div><h4>Sweetened beverages and incident heart failure.</h4><i>Zhang Z, Zhang K, Sun Y, Yu B, ... Xia F, Wang N</i><br /><b>Aims</b><br />Recent studies have demonstrated the associations of the consumption of different beverages with cardiometabolic diseases, whereas no studies have investigated such associations in heart failure (HF). Thus, this study aimed to explore the associations of the consumption of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and pure fruit/vegetable juices (PJs) with the risk of incident HF.<br /><b>Methods</b><br />This prospective cohort study included 209,829 participants in the UK Biobank who completed at least one 24-h diet questionnaire and who were free of baseline HF. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).<br /><b>Results</b><br />During a median follow-up of 9.9 years, 4,328 incident HF cases were recorded. Compared to corresponding nonconsumers, individuals who consumed >2 L/week SSBs or ASBs had an increased risk of HF (HR: 1.22, 95% CI: 1.08-1.38 and HR: 1.30, 95% CI: 1.16-1.47, respectively) in the multivariate adjusted model. An inverse association was observed between the consumption of >0-1 L/week PJs and the risk of HF (HR: 0.90, 95% CI: 0.83-0.98). Additionally, a significant interaction was observed between PJ consumption and sleep duration on HF risk (P for interaction =0.030).<br /><b>Conclusions</b><br />Increased consumption of SSBs or ASBs may be an independent risk factor for HF, whereas moderate intake of PJs may have a protective effect on HF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur J Prev Cardiol: 13 May 2023; epub ahead of print</small></div>

<div><h4>Pulmonary Artery Catheter Use and Risk of In-Hospital Death in Heart Failure Cardiogenic Shock.</h4><i>Kanwar MK, Blumer V, Zhang Y, Sinha S, ... Burkhoff D, Kapur NK</i><br /><b>Background</b><br />Pulmonary artery catheters (PACs) are increasingly used to guide management decisions in cardiogenic shock (CS).<br /><b>Objectives</b><br />The goal of this study was to determine if PAC use was associated with a lower risk of in-hospital mortality in CS due to acute heart failure (HF-CS).<br /><b>Methods</b><br />Multicenter, retrospective, observational study of CS patients hospitalized between 2019-2021 at 15 US hospitals participating in the Cardiogenic Shock Working Group registry. The primary endpoint was in-hospital mortality. Inverse probability of treatment-weighted logistic regression models were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CI), accounting for multiple variables at admission. The association between timing of PAC placement and in-hospital death was also analyzed.<br /><b>Results</b><br />A total of 1055 HF-CS patients were included of whom 834 (79%) received a PAC during their hospitalization. In-hospital mortality risk for the cohort was 24.7% (n=261). PAC use was associated with lower adjusted in-hospital mortality risk (22.2% vs. 29.8%, OR 0.68, 95% CI 0.50-0.94). Similar associations were found across SCAI stages of shock, both at admission and at maximum SCAI stage during hospitalization. Early PAC use (≤ 6 hours of admission) was observed in 220 (26%) PAC recipients and associated with a lower adjusted risk of in-hospital mortality compared to delayed (≥ 48 hours) or no PAC use (17.3% vs. 27.7%, OR 0.54, 95% CI 0.37-0.81).<br /><b>Conclusions</b><br />This observational study supports PAC use, as it was associated with decreased in-hospital mortality in HF-CS, especially if performed within 6 hours of hospital admission.<br /><b>Condensed abstract</b><br />An observational study from the Cardiogenic Shock Working Group registry of 1,055 patients with heart failure related cardiogenic shock showed that pulmonary artery catheter (PAC) use was associated with lower adjusted in-hospital mortality risk (22.2% vs. 29.8%, OR 0.68, 95% CI 0.50-0.94) compared to outcomes in patients managed without PAC. Early PAC use (≤ 6 hours of admission) was associated with a lower adjusted risk of in-hospital mortality compared to delayed (≥ 48 hours) or no PAC use (17.3% vs. 27.7%, OR 0.54, 95% CI 0.37-0.81).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 13 May 2023; epub ahead of print</small></div>

<div><h4>Infections following Left Ventricular Assist Device Implantation and 1-Year Health-related Quality of Life.</h4><i>Zhou S, Yang G, Hou H, Zhang M, ... Likosky DS, Michigan Congestive Heart Failure Investigators</i><br /><b>Background</b><br />Left ventricular assist device (LVAD) implantation leads to substantial and sustained improvement in health-related quality of life (HRQOL) among patients. Infection following device implantation remains an important and frequent complication and adversely affects patient-reported HRQOL.<br /><b>Methods</b><br />Patients in The Society of Thoracic Surgeons\' Interagency Registry for Mechanically Assisted Circulatory Support receiving a primary LVAD between April 2012 to October 2016 were included. The primary exposure was one-year post-implant infection, characterized by: (1) any infection; (2) total number of infections and (3) type (LVAD-specific, LVAD-related, non-LVAD). The association between infection and the primary composite adverse outcome (defined as EuroQoL Visual Analog Scale <65, too sick to complete the survey, or death at 1-year) was estimated using inverse probability weighting and Cox regression.<br /><b>Results</b><br />The study cohort included 11,618 patients from 161 medical centers with 4,768 (41.0%) patients developing an infection, and 2,282 (19.6%) patients having >1 infection during the follow up period. The adjusted odds ratio (OR<sub>adj</sub>) for the primary composite adverse outcome was 1.22 (95%CI 1.19-1.24, p<0.001) for each additional infection. Each additional infection was associated with a 3.49% greater probability of the primary composite outcome and was associated with worse performance across multiple dimensions of HRQOL as assessed by the EQ-5D for patients who survived to 1 year.<br /><b>Conclusions</b><br />For patients undergoing LVAD implantation, each additional infection within the first post-implantation year was associated with an incremental negative effect on survival free of impaired HRQOL.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 13 May 2023; epub ahead of print</small></div>

<div><h4>Lung Transplant Survival with Past and Concomitant Cardiac Revascularization.</h4><i>Tran T, Kashem MA, Firoz A, Yanagida R, Shigemura N, Toyoda Y</i><br /><b>Background</b><br />Coronary artery disease (CAD) is common among lung transplant (LTx) candidates and has historically been viewed as a contraindication to the procedure. Survival outcomes of lung transplant recipients with concomitant coronary artery disease who had prior or perioperative revascularization remain a topic of conversation.<br /><b>Methods</b><br />A retrospective analysis of all single and double lung transplant patients from Feb-2012 to Aug-2021 at a single center was performed (n = 880). Patients were split into 4 groups: (1) those who received a preoperative percutaneous coronary intervention, (2) those who received pre-operative coronary artery bypass grafting (CABG), (3) those who received CABG during transplantation, and (4) those who had lung transplantation without revascularization. Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. P-value <0.05 was considered significant.<br /><b>Results</b><br />Most patients receiving LTx were males = and white. Pump type (p 0.810), total ischemic time (p 0.994), warm ischemic time (p 0.479), length of stay (p 0.751), and lung allocation score (p 0.332) were not significantly different between the four groups. The no revascularization group was younger than the other groups (p<0.01). The diagnosis of Idiopathic Pulmonary Fibrosis was predominant in all groups except the no revascularization group. The pre-CABG group had a higher portion of single LTx procedures (p 0.014). Kaplan-Meier analysis showed no significantly different survival rates after post-LTx between the groups (p 0.471). Cox Regression analysis showed diagnosis significantly impacted survival rates (p 0.009).<br /><b>Conclusions</b><br />Preoperative or intraoperative revascularization did not affect survival outcomes in lung transplant patients. Selected patients with coronary artery disease may benefit when intervened during lung transplant procedures.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 13 May 2023; epub ahead of print</small></div>

<div><h4>Machine Learning-Based Phenogrouping in Mitral Valve Prolapse Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events.</h4><i>Huttin O, Girerd N, Jobbe-Duval A, Constant Dit Beaufils AL, ... Selton-Suty C, Le Tourneau T</i><br /><b>Background</b><br />Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in patients with mitral valve prolapse (MVP). In this setting, it is likely that an unsupervised approach using machine learning may improve their risk assessment.<br /><b>Objectives</b><br />This study used machine learning to improve the risk assessment of patients with MVP by identifying echocardiographic phenotypes and their respective association with myocardial fibrosis and prognosis.<br /><b>Methods</b><br />Clusters were constructed using echocardiographic variables in a bicentric cohort of patients with MVP (n = 429 patients, 54 ± 15 years) and subsequently investigated for their association with myocardial fibrosis (assessed by cardiac magnetic resonance) and cardiovascular outcomes.<br /><b>Results</b><br />Mitral regurgitation (MR) was severe in 195 (45%) patients. Four clusters were identified: cluster 1 comprised no remodeling with mainly mild MR, cluster 2 was a transitional cluster, cluster 3 included significant left ventricular (LV) and left atrial (LA) remodeling with severe MR, and cluster 4 included remodeling with a drop in LV systolic strain. Clusters 3 and 4 featured more myocardial fibrosis than clusters 1 and 2 (P < 0.0001) and were associated with higher rates of cardiovascular events. Cluster analysis significantly improved diagnostic accuracy over conventional analysis. The decision tree identified the severity of MR along with LV systolic strain <21% and indexed LA volume >42 mL/m<sup>2</sup> as the 3 most relevant variables to correctly classify participants into 1 of the echocardiographic profiles.<br /><b>Conclusions</b><br />Clustering enabled the identification of 4 clusters with distinct echocardiographic LV and LA remodeling profiles associated with myocardial fibrosis and clinical outcomes. Our findings suggest that a simple algorithm based on only 3 key variables (severity of MR, LV systolic strain, and indexed LA volume) may help risk stratification and decision making in patients with MVP. (Genetic and Phenotypic Characteristics of Mitral Valve Prolapse; NCT03884426 and Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse [MVP STAMP]; NCT02879825).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 13 May 2023; epub ahead of print</small></div>

<div><h4>Sodium-Glucose Cotransporter 2 Inhibitor Use in Early-Phase Acute Coronary Syndrome with Severe Heart Failure.</h4><i>Kanaoka K, Iwanaga Y, Nakai M, Nishioka Y, ... Saito Y, Imamura T</i><br /><b>Aims</b><br />Sodium-glucose cotransporter 2 inhibitor (SGLT2i) improves clinical outcomes in patients with heart failure (HF), but has limited evidence of SGLT2i use on early-phase acute coronary syndrome (ACS). We determined association of early SGLT2i use compared with either non-SGLT2i or dipeptidyl peptidase 4 inhibitor (DPP4i) in hospitalized patients with ACS.<br /><b>Methods and results</b><br />This retrospective cohort study that used the Japanese nationwide administrative claims database included patients hospitalized with ACS aged ≥ 20 years between April 2014 and March 2021. The primary outcome was a composite of all-cause mortality or HF/ACS rehospitalization. Using 1:1 propensity score matching, the association with outcomes of the early SGLT2i use (≤14 days after admission) compared with non-SGLT2i or DPP4i was determined according to the HF treatment. Among 388 185 patients included, 115 612 and 272 573 with and without severe HF, respectively. Compared to non-SGLT2i users, the SGLT2i users had a lower hazard ratio (HR) with the primary outcome (HR: 0.83, 95% confidence interval [CI]: 0.76-0.91, p < 0.001) in the severe HF group; however, there was no significant difference in the non-severe HF group (HR: 0.92, 95% CI: 0.82-1.03, p = 0.16). SGLT2i use showed a lower risk of the outcome in patients with severe HF and diabetes compared with DPP4i (HR: 0.83, 95% CI: 0.69-1.00, p = 0.049).<br /><b>Conclusion</b><br />SGLT2i use in patients with early-phase ACS showed a lower risk of primary outcome in patients with severe HF but the effect was not apparent in patients without severe HF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 12 May 2023; epub ahead of print</small></div>

<div><h4>Intermediate-term Outcomes of Complement Inhibition for Prevention of Antibody-Mediated Rejection in Immunologically High-risk Heart Allograft Recipients.</h4><i>Coutance G, Kobashigawa JA, Kransdorf E, Loupy A, ... Kittleson M, Patel JK</i><br /><AbstractText>Allosensitization represents a major barrier to heart transplantation (HTx). We previously reported favorable 1-year outcomes of complement inhibition at transplant in highly sensitized recipients. We now report a longer follow-up. In this single-arm trial (NCT02013037), 20 patients with panel reactive antibodies ≥70% and pre-formed donor-specific antibodies received eculizumab during the first two months post-transplant. The primary endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction. Median follow-up was 4.8 years. Beyond the first year post-transplant, there were no episodes of pAMR2 or greater and no LV dysfunction. There were three deaths, one episode of pAMR1, and one patient with minimal de novo cardiac allograft vasculopathy. Compared to a matched-control group, we observed a non-statistically significant benefit of eculizumab with a lower incidence of primary endpoint or death (primary endpoint: HR=0.50, 95%CI=0.15-1.67, p=0.26; mortality: HR=0.51, 95%CI=0.13-2.07, p=0.35). Our results support the utility of complement inhibition for high-immunological risk recipients. DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 12 May 2023; epub ahead of print</small></div>

<div><h4>Use of Exception Status Listing and Related Outcomes During Two Heart Allocation Policy Periods.</h4><i>Golbus JR, Ahn YS, Lyden GR, Nallamothu BK, ... Walsh MN, Colvin M</i><br /><b>Background</b><br />The October 2018 update to the heart allocation policy was intended to decrease exception status requests, whereby candidates are listed at a specific status due to perceived need despite not meeting pre-specified criteria of illness severity. We assessed use of exception status and waitlist outcomes before and after the 2018 policy.<br /><b>Methods</b><br />We used data from the Scientific Registry of Transplant Recipients on adult heart transplant candidates listed from 2015-2021. We assessed (1) use of exception status across patient characteristics between the two periods and (2) transplant rate and waitlist mortality or delisting due to deterioration in each period. Patients listed by exception versus standard criteria were compared with multivariable logistic regression and waitlist outcomes assessed using Cox proportional hazards models with medical urgency and exception status as time-dependent covariates.<br /><b>Results</b><br />During the study period (n=19,213), heart transplants under exception status increased post-policy, from 10.0% to 32.3%, with 20.6% of transplants performed for patients at status 2 exception. Exception status candidates post-policy were more frequently Black or Hispanic/Latino, less likely to have hypertrophic or restrictive cardiomyopathy, and had worse hemodynamics. Exception status listing was associated with higher transplant rates in both periods. Post-policy, candidates listed status 1 exception had a lower likelihood for waitlist mortality or delisting (HR, 0.60; 95% CI, 0.37-0.99; P=0.05).<br /><b>Conclusions</b><br />Under the 2018 policy, exception status listings dramatically increased. The policy change shifted the population of patients listed by exception status and affected waitlist mortality, which suggests a need to further evaluate the policy\'s impact.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 12 May 2023; epub ahead of print</small></div>

<div><h4>Fibrotic Plaque and Microvascular Dysfunction Predict Early Cardiac Allograft Vasculopathy Progression After Heart Transplantation: The Early Post Transplant Cardiac Allograft Vasculopathy Study.</h4><i>Chih S, Chong AY, Džavík V, So DY, ... Beanlands RSB, Ross HJ</i><br /><b>Background</b><br />Early cardiac allograft vasculopathy (CAV) prognostication is needed to improve long-term outcomes after heart transplantation. We characterized first year posttransplant coronary anatomic-physiologic alterations to determine predictors of early CAV progression.<br /><b>Methods</b><br />Heart transplant recipients at 2 institutions (enrolled January 2018 to March 2021) underwent prospective evaluation 3 and 12-month posttransplant with angiography and left anterior descending artery intravascular ultrasound, optical coherence tomography, fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance measurements. CAV progression was assessed by intravascular ultrasound change in percentage intimal volume from baseline to 12-month follow-up.<br /><b>Results</b><br />Eighty-two patients (mean age, 51 years; 60% men) completed evaluation at mean 13.8 and 56.3 weeks posttransplant. Donor atherosclerosis (baseline intravascular ultrasound maximal intimal thickness, ≥0.5 mm) was evident in 50%. De novo (follow-up maximal intimal thickness, ≥0.5 mm) and rapidly progressive CAV (maximal intimal thickness, ≥0.5-mm increase from baseline) developed in 24% and 13%, respectively. On optical coherence tomography, baseline to follow-up median intimal volume increased 42% (0.58 mm<sup>3</sup>/mm), percentage intimal volume increased 44% (4.6%), vessel volume decreased 4% (-0.50 mm<sup>3</sup>/mm) and lumen volume decreased 9% (-1.02 mm<sup>3</sup>/mm); <i>P</i><0.05 for all. Fibrotic plaque was the predominant morphology: baseline, 29% and follow-up, 50%. Coronary physiology was abnormal in 41% at baseline and 45% at follow-up, with 1 in 5 patients having microvascular dysfunction (index of microcirculatory resistance, ≥25). On multivariable linear regression analysis, recipient male sex, fibrotic plaque, and index of microcirculatory resistance were independent predictors of coronary disease progression.<br /><b>Conclusions</b><br />Fibrotic plaque on optical coherence tomography and index of microcirculatory resistance early posttransplant predict CAV progression in the first year of transplantation.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT03217786.<br /><br /><br /><br /><small>Circ Heart Fail: 11 May 2023:e010173; epub ahead of print</small></div>

<div><h4>Tolerability and beneficial effects of sacubitril/valsartan on systemic right ventricular failure.</h4><i>Nederend M, Kiès P, Regeer MV, Vliegen HW, ... Jongbloed MRM, Egorova AD</i><br /><b>Objective</b><br />Patients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are prone to sRV dysfunction. Pharmacological options for sRV failure remain poorly defined. This study aims to investigate the tolerability and effects of sacubitril/valsartan on sRV failure in adult patients with sRV.<br /><b>Methods</b><br />In this two-centre, prospective cohort study, all consecutive adult patients with symptomatic heart failure and at least moderately reduced sRV systolic function were initiated on sacubitril/valsartan and underwent structured follow-up.<br /><b>Results</b><br />Data of 40 patients were included (40% female, 30% ccTGA, median age 48 (44-53) years). Five patients discontinued therapy during titration. Median follow-up was 24 (12-36) months. The maximal dose was tolerated by 49% of patients. No episodes of hyperkalaemia or renal function decline occurred. Six-minute walking distance increased significantly after 6 months of treatment (569±16 to 597±16 m, p=0.016). Serum N-terminal-prohormone brain natriuretic peptide (NT-proBNP) levels decreased significantly after 3 months (567 (374-1134) to 404 (226-633) ng/L, p<0.001). Small, yet consistent echocardiographic improvements in sRV function were observed after 6 months (sRV global longitudinal strain: -11.1±0.5% to -12.6±0.7%, p<0.001, and fractional area change: 20% (16%-24%) to 26% (19%-30%), p<0.001). The linear mixed-effects model illustrated that after first follow-up moment, no time effect was present for the parameters.<br /><b>Conclusions</b><br />Treatment with sacubitril/valsartan was associated with a low rate of adverse effects in this adult sRV cohort. Persisting improvement in 6-minute walking test distance, NT-proBNP levels and echocardiographic parameters of sRV function was observed in an on-treatment analysis and showed no differential response based on sex or anatomy.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 11 May 2023; epub ahead of print</small></div>

<div><h4>Changes in cardiac time intervals over a decade and the risk of incident heart failure: The Copenhagen City heart study.</h4><i>Alhakak AS, Olsen FJ, Skaarup KG, Lassen MCH, ... Møgelvang R, Biering-Sørensen T</i><br /><b>Background</b><br />The cardiac time intervals include the isovolumic contraction time (IVCT), the left ventricular ejection time (LVET), the isovolumic relaxation time (IVRT) and the combination of all the cardiac time intervals in the myocardial performance index (MPI) (defined as [(IVCT+IVRT)/LVET)]. Whether the cardiac time intervals change over time and which clinical factors that accelerate these changes is not well-established. Additionally, whether these changes are associated with subsequent heart failure (HF), remains unknown.<br /><b>Methods</b><br />We investigated participants from the general population (n = 1064) who had an echocardiographic examination including color tissue Doppler imaging performed in both the 4th and 5th Copenhagen City Heart Study. The examinations were performed 10.5 years apart.<br /><b>Results</b><br />The IVCT, LVET, IVRT and MPI increased significantly over time. None of the investigated clinical factors were associated with increase in IVCT. Systolic blood pressure (standardized β= - 0.09) and male sex (standardized β= - 0.08) were associated with an accelerated decrease in LVET. Age (standardized β=0.26), male sex (standardized β=0.06), diastolic blood pressure (standardized β=0.08), and smoking (standardized β=0.08) were associated with an increase in IVRT, while HbA1c (standardized β= - 0.06) was associated with a decrease in IVRT. Increasing IVRT over a decade was associated with an increased risk of subsequent HF in participants aged <65 years (per 10 ms increase: HR 1.33; 95%CI (1.02-1.72), p = 0.034).<br /><b>Conclusion</b><br />The cardiac time increased significantly over time. Several clinical factors accelerated these changes. An increase in IVRT was associated with an increased risk of subsequent HF in participants aged <65 years.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 11 May 2023; epub ahead of print</small></div>

<div><h4>Biomarkers for the diagnosis of heart failure in people with diabetes: A consensus report from diabetes technology society.</h4><i>Yeung AM, Huang J, Pandey A, Hashim IA, ... Wu AHB, Klonoff DC</i><br /><AbstractText>Diabetes Technology Society assembled a panel of clinician experts in diabetes, biomarker screening, and heart failure to review the current evidence on biomarker screening of people with diabetes (PWD) for heart failure (HF), who are, by definition, at risk for HF (Stage A HF). This consensus report reviews features of HF in PWD from the perspectives of 1) epidemiology, 2) classification of stages, 3) pathophysiology, 4) biomarkers for diagnosing, 5) biomarker assays, 6) diagnostic accuracy of biomarkers, 7) benefits of biomarker screening, 8) consensus recommendations for biomarker screening, 9) stratification of Stage B HF, 10) echocardiographic screening, 11) management of Stage A and Stage B HF, and 12) future directions. The Diabetes Technology Society panel recommends 1) biomarker screening with one of two circulating natriuretic peptides (B-type natriuretic peptide or N-terminal prohormone of B-type natriuretic peptide), 2) beginning screening five years following diagnosis of type 1 diabetes (T1D) and at the diagnosis of type 2 diabetes (T2D), 3) beginning routine screening no earlier than at age 30 years for T1D (irrespective of age of diagnosis) and at any age for T2D, 4) screening annually, and 5) testing any time of day. The panel also recommends that an abnormal biomarker test defines asymptomatic preclinical HF (Stage B HF). This diagnosis requires follow-up using transthoracic echocardiography for classification into one of four subcategories of Stage B HF, corresponding to risk of progression to symptomatic clinical HF (Stage C HF). These recommendations will allow identification and management of Stage A and Stage B HF in PWD to prevent progression to Stage C HF or advanced HF (Stage D HF).</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Prog Cardiovasc Dis: 11 May 2023; epub ahead of print</small></div>