<div><h4>The impact of ferric derisomaltose on cardiovascular and non-cardiovascular events in patients with anemia, iron deficiency and heart failure with reduced ejection fraction.</h4><i>Ray R, Ford I, Cleland JGF, Graham F, ... Squire I, Kalra PR</i><br /><b>Background</b><br />In some countries, intravenous (IV) ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN trial.<br /><b>Method and results</b><br />IRONMAN enrolled patients with heart failure, left ventricular ejection fraction (LVEF) ≤45% and iron deficiency (ferritin <100 µg/L or TSAT <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women; <13 g/dL for men). Patients were randomized, open-label, to FDI (n=397) or usual care (n=374) and followed for a median of 2.6 years. The primary endpoint, recurrent hospitalization for heart failure and cardiovascular death, occurred less frequently for those assigned to FDI (rate ratio 0.78 [95% CI 0.61 - 1.01); p=0.063). First-event analysis for cardiovascular death or hospitalization for heart failure, less affected by the COVID pandemic, gave similar results (hazard ratio 0.77 [95% CI 0.62 - 0.96]; p=0.022). Patients randomized to FDI reported a better Minnesota Living with Heart Failure quality-of-life, for overall (p = 0.013) and physical-domain (p = 0.00093) scores at four months.<br /><b>Conclusion</b><br />In patients with iron deficiency anemia and heart failure with reduced LVEF, IV FDI improves quality of life and may reduce cardiovascular events.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 03 Nov 2023; epub ahead of print</small></div>

<div><h4>Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-Infected Donors in the Current Era.</h4><i>Amancherla K, Feurer ID, Rega SA, Cluckey A, ... Shah AS, Schlendorf KH</i><br /><AbstractText>Transplantation of hearts from hepatitis C-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral (DAA) therapies for treatment and cure of hepatitis C virus (HCV). While historical data from the pre-DAA era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test positive (NAT+) donors and the development of CAV in the DAA era remains unclear. We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first-year post-transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a sub-sample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound performed, we compared development of rapidly-progressive CAV (RP-CAV), defined as an increase in maximal intimal thickening of ≥ 0.5 mm in matched vessel segments during the first-year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥ 1 over the first-year post-HT compared to recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of RP-CAV. These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 29 Oct 2023; epub ahead of print</small></div>

<div><h4>The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.</h4><i>Stern LK, Grodin JL, Maurer MS, Ruberg FL, ... Kittleson MM, Patel JK</i><br /><b>Background</b><br />CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997-2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated patient outcomes in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials.<br /><b>Methods and results</b><br />This paper describes the design and methodology of CARS including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%) and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%).<br /><b>Conclusions</b><br />CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 29 Oct 2023; epub ahead of print</small></div>

<div><h4>The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.</h4><i>Moayedi Y, Truby LK, Foroutan F, Han J, ... Ross HJ, Khush KK</i><br /><b>Background</b><br />Primary Graft Dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplant (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were to 1) assess the incidence of severe PGD in an international cohort, 2) evaluate the performance of the most validated PGD risk tool, the RADIAL score, in a contemporary cohort, and 3) redefine clinical risk factors for severe PGD in the current era of HT.<br /><b>Methods</b><br />This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada, and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis and its calibration was assessed by plotting the percentage of PGD predicted versus observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability.<br /><b>Results</b><br />A total of 2,746 patients have been enrolled in the registry to date, including 2,015 (73.4%) from North America, and 731 (26.6%) from Europe. 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (p-value for trend by difference sign test = 0.004). The Kaplan Meier estimate for 1-year survival was 75.7% [95%CI 69.4-80.9%] in patients with severe PGD as compared to 94.4% [95% CI 93.5-95.2%] in those without severe PGD (log-rank p-value <0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD with an AUC of 0.53 (95%CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31 - 4.43), durable LVAD support (OR 1.77, 95% CI 1.13 - 2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02 - 1.41) were associated with an increased risk of severe PGD.<br /><b>Conclusions</b><br />Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 29 Oct 2023; epub ahead of print</small></div>

<div><h4>Changing Strategy Between Bridge to Transplant and Destination LVAD Therapy After The First 3 Months: Analysis of the STS- INTERMACS Database.</h4><i>Rali AS, Inampudi C, Zalawadiya S, Shah A, ... Kirklin JK, Stevenson LW</i><br /><b>Background</b><br />Left ventricular assist devices (LVADs) have been implanted as bridge to transplantation (BTT), bridge to candidacy (BTC) or destination therapy (DT) based on relative and absolute contraindications to transplantation. Multiple factors may lead to change in the strategy of support after LVAD implantation.<br /><b>Methods</b><br />From INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) 2012-2020, 11,262 patients survived to 3 months on continuous flow LVADs with intent of BTT or DT. Pre-implant characteristics and early events post-LVAD were analyzed in relation to changes in BTT or DT strategy during the next 12 months.<br /><b>Results</b><br />Among 3216 BTT patients at 3 months, later transplant de-listing or death without transplant occurred in 536 (16.7%) and, was more common with age, Profiles 1-2, renal dysfunction, and independently for prior cardiac surgery (HR 1.25, 95% CI 1.04-1.51, p = 0.02). Post-LVAD events of infections, gastrointestinal bleeding, stroke, and right heart failure defined by inotropic therapy predicted de-listing and death, as did in-hospital location at 3 months (HR 1.67, 95% CI 1.20-2.33, p =0.0024). Of 8046 patients surviving to 3 months with intent as destination therapy, 750 (9.3%) subsequently underwent listing or transplant, often with initial history of acute HF (HR 1.70, 95% CI 1.27-2.27, p = 0.0012) or malnutrition-cachexia (1.73, 95% CI 1.14-2.63, p = 0.0099). Multiple gastrointestinal bleeding events (≥4) with LVAD increased transition from BTT to DT (HR 4.22, 95% CI 1.46-12.275, p = 0.0078) but also from DT to BTT (HR 5.17, 95% CI 1.92-13.9, p = 0.0011).<br /><b>Conclusions</b><br />Implant strategies change over time in relation to pre-implant characteristics and adverse events post implant. Pre-implant recognition of factors predicting later change in implant strategy will refine initial triage, while further reduction of post-LVAD complications will expand options including eventual consideration of heart transplant.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 26 Oct 2023; epub ahead of print</small></div>

<div><h4>Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation.</h4><i>Gondi KT, Hammer Y, Yosef M, Golbus JR, ... Murthy VL, Konerman MC</i><br /><b>Background</b><br />PET myocardial flow reserve (MFR) is a noninvasive method to detect cardiac allograft vasculopathy in heart transplant (HT) recipients. There is limited data on longitudinal change and predictors of MFR following HT.<br /><b>Methods</b><br />We conducted a retrospective analysis of HT recipients undergoing PET MPI at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors, and prognostic value of MFR after HT.<br /><b>Results</b><br />183 HT recipients underwent 658 PET studies. Average MFR was 2.34 ± 0.70. MFR initially increased in the first three years following HT (+0.12 per year, P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P <0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mTOR inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (p <0.001), hypertension (P <0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4-13.4, P <0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4-3.9, P <0.001) was associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization.<br /><b>Conclusion</b><br />MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk factor modification and treatment with higher-intensity statin therapy and MTI are associated with a higher MFR.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Novel Nebulized Milrinone Formulation for the Treatment of Acute Heart Failure Requiring Inotropic Therapy: A Phase 1 Study.</h4><i>Cox ZL, Dalia T, Goyal A, Fritzlen J, ... Sauer AJ, Haglund NA</i><br /><b>Background</b><br />Non-intravenous inotropic delivery options are needed for patients with inotropic dependent heart failure (HF) to reduce the costs, infection, and thrombotic risks associated with chronic central venous catheters and home infusion services.<br /><b>Methods</b><br />We developed a novel, concentrated formulation of nebulized milrinone for inhalation and evaluated the feasibility, safety, and pharmacokinetic profile in a prospective, single-arm, Phase I clinical trial. We enrolled 10 patients with Stage D HF requiring inotropic therapy during an acute HF hospital admission. Milrinone 60mg/4mL was inhaled via nebulization three times daily for 48 hours. The co-primary outcomes were adverse events and pharmacokinetic profile of inhaled milrinone. Acute changes in hemodynamic parameters were secondary outcomes.<br /><b>Results</b><br />A concentrated nebulized milrinone formulation was well tolerated without hypotensive events, arrhythmias, or inhalation-related adverse events requiring discontinuation. Nebulized milrinone produced serum concentrations in the goal therapeutic range with a median plasma milrinone trough concentration of 39 (17 - 66) ng/ml and a median peak concentration of 207 (134 - 293) ng/ml. There were no serious adverse events. From baseline to 24-hours, mean pulmonary artery saturation increased (60±7% to 65±5%; p=0.001), and mean cardiac index increased (2.0±0.5 ml/min/1.73m<sup>2</sup> to 2.5±0.1 ml/min/1.73m<sup>2</sup>; p=0.001) with nebulized milrinone.<br /><b>Conclusions</b><br />In a proof-of-concept study, a concentrated, nebulized milrinone formulation for inhalation was safe and produced therapeutic serum milrinone concentrations. Nebulized milrinone was associated with improved hemodynamic parameters of cardiac output in an advanced HF population. These promising results require further investigation in a longer-term trial in patients with inotrope-dependent advanced HF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 21 Oct 2023; epub ahead of print</small></div>

<div><h4>Isovolumic Contraction Velocity in Heart Failure with Reduced Ejection Fraction and Effect of Sacubitril/Valsartan: The PROVE-HF Study.</h4><i>Omar AMS, Murphy S, Felker GM, Piña I, ... Januzzi JL, Contreras J</i><br /><b>Objectives</b><br />To assess tissue Doppler-derived mitral annular isovolumic contraction velocity (ICV) after starting sacubitril/valsartan (sac/val) for the treatment of heart failure with reduced ejection fraction (HFrEF; left ventricular [LV] EF <40%).<br /><b>Background</b><br />ICV may inform load-independent systolic function; combining ICV and LVEF may improve assessment of LV contractility.<br /><b>Methods</b><br />Among 651 HFrEF participants treated with sac/val, echocardiograms were performed at baseline, 6, and 12 months. Pre-treatment median ICV and LVEF were used for classification to predict LV reverse remodeling, health status using the Kansas City Cardiomyopathy Questionnaire, and biomarker concentrations.<br /><b>Results</b><br />The mean age was 64.6±12.4 years, and 28% were women, baseline LVEF: 28.9±6.9%. Compared to baseline, median ICV increased post sac/val therapy (4.6 [3.5, 6.1] vs. 4.9 [3.6, 6.4], p=0.005). ICV added value to separate and combined models of biomarkers, clinical, and echocardiographic variables for prediction of post-therapy EF recovery. Classification using baseline ICV/EF yielded relatively equal numbers in 4 groups based on low/high ICV or LVEF. Most deleterious results for remodeling, health status, and biomarkers were found in low-ICV/low-EF patients, while high ICV/high EF had the best profiles; other groups were intermediate. Significant shifts towards better ICV/EF profiles were noted post sac/val treatment compared to baseline, with doubling of high-ICV/high-EF [241(60%) vs. 123(31%)] and 78% reduction of low-ICV/low-EF [28(7%) vs. 125(32%)].<br /><b>Conclusions</b><br />In HFrEF, ICV adds to the profiling of systolic function and represents an independent predictor of reverse cardiac remodeling after treatment with sac/val. ICV changes may be used for assessment of treatment response.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 07 Oct 2023; epub ahead of print</small></div>

<div><h4>The HFSA Advanced Heart Failure and Transplant Cardiology Fellowship Consensus Conference.</h4><i>Drazner MH, Ambardekar AV, Berlacher K, Blumer V, ... Zieroth S, Teerlink JR</i><br /><AbstractText>There is waning interest amongst cardiology trainees in pursuing an Advanced Heart Failure/Transplant Cardiology (AHFTC) fellowship as evidenced by fewer applicants in the NRMP match to this specialty. This trend has generated considerable attention across the heart failure (HF) community. In response, the Heart Failure Society of America convened the AHFTC Fellowship Task Force with a charge to develop strategies to increase the value proposition of an AHFTC fellowship. Subsequently, the HFSA sponsored the AHFTC Fellowship Consensus Conference April 26 - 27, 2023. Prior to the conference, interviews of 44 expert stakeholders diverse across geography, site of practice (traditional academic medical center or other centers), specialty/area of expertise, sex, and stage of career were conducted virtually. Based on these interviews, potential solutions to address the declining interest in AHFTC fellowship were categorized into five themes: 1. Alternative training pathways; 2. Regulatory and compensation; 3. Educational improvements; 4. Exposure and marketing for pipeline development; and 5. Quality of life and mental health. These themes provided structure to the deliberations of the AHFTC Fellowship Consensus Conference. The recommendations from the Consensus Conference were subsequently presented to the HFSA Board of Directors (BOD) to inform strategic plans and interventions. The HFSA BOD later reviewed and approved submission of this document. The purpose of this communication is to provide the HF community with an update summarizing the processes employed and concepts which emerged from the work of the HFSA AHFTC Fellowship Task Force and Consensus Conference.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 30 Sep 2023; epub ahead of print</small></div>

<div><h4>Safety indicators in patients receiving high-intensity care after hospital admission for acute heart failure: the STRONG-HF trial.</h4><i>Tomasoni D, Davison B, Adamo M, Pagnesi M, ... Cotter G, Metra M</i><br /><b>Background</b><br />STRONG-HF demonstrated the safety and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) with high intensity care (HIC) compared to usual care in patients hospitalized for acute heart failure (HF). In the HIC group, the following safety indicators were used to guide up-titration: estimated glomerular filtration rate [eGFR] <30ml/min/1.73m<sup>2</sup>, serum potassium >5.0 mmol/L, systolic blood pressure (SBP) <95mmHg, heart rate <55bpm, NT-proBNP concentration >10% higher than pre-discharge values.<br /><b>Methods</b><br />We examined the impact of protocol-specified safety indicators on achieved dose of GDMT and clinical outcomes.<br /><b>Results</b><br />Three-hundred-thirteen of the 542 patients in the HIC arm (57.7%) met at least one safety indicator at any follow-up visit 1 to 6 weeks after discharge. As compared to those without, patients meeting at least one safety indicator had more severe HF symptoms, lower SBP and higher heart rate at baseline and achieved a lower average percentage of GDMT optimal doses (mean difference vs the HIC arm patients not reaching any safety indicator, -11.0% [95% CI -13.6 to -8.4%], P<0.001). The primary endpoint of 180-day all-cause death or HF re-admission occurred in 15.0% of patients with any safety indicator versus 14.2% of those without (adjusted hazard ratio [HR] 0.84, 95% CI 0.48 to 1.46, P=0.540). None of each safety indicator, considered alone, was significantly associated with the primary endpoint, but SBP < 95mmHg was associated with a trend towards increased 180 days all-cause mortality (adjusted HR = 2.68 [0.94 to 7.64]; P = 0.065) and eGFR drop to < 30ml/min/1.73m<sup>2</sup> with more HF readmissions (adjusted HR 3.60 [1.22 to 10.60]; p = 0.0203). The occurrence of a safety indicator was associated with a smaller 90-day improvement in EQ-5D VAS (adjusted mean difference -3.32 points, 95% CI -5.97 to -0.66, P=0.015).<br /><b>Conclusions</b><br />Among patients with acute HF enrolled in STRONG-HF in the HIC arm, the occurrence of any safety indicator was associated with the administration of slightly lower GDMT doses and less improvement in quality of life but with no significant increase in the primary outcome of 180-day HF readmission or death when appropriately addressed according to the study protocol.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 29 Sep 2023; epub ahead of print</small></div>

<div><h4>Outcomes of Patients Transferred to Tertiary Care Centers for Treatment of Cardiogenic Shock: A Cardiogenic Shock Working Group Analysis: Outcomes of Patients Transferred for Treatment of Cardiogenic Shock.</h4><i>Garan AR, Kataria R, Li B, Sinha S, ... Burkhoff D, Kapur NK</i><br /><b>Background</b><br />Consensus recommendations for cardiogenic shock (CS) advise transfer of patients in need of advanced options beyond the capability of \'spoke\' centers to tertiary/ \'hub\' centers with higher capabilities. However, outcomes associated with such transfers are largely unknown, beyond those reported in individual health networks.<br /><b>Objectives</b><br />To analyze a contemporary, multicenter CS cohort with an aim to compare characteristics and outcomes of patients between transfer (between spoke and hub center) and non-transfer cohorts (those primarily admitted to a hub center), for both acute myocardial infarction (AMI-CS) and heart failure related (HF-CS) shock. We also aim to identify clinical characteristics of the transfer cohort that are associated with in-hospital mortality.<br /><b>Methods</b><br />The Cardiogenic Shock Working Group (CSWG) registry is a national, multicenter, prospective registry including high volume (mostly hub) CS centers. Fifteen U.S. sites contributed data for this analysis from 2016-2020.<br /><b>Results</b><br />Of 1890 consecutive CS patients enrolled into the CSWG registry, 1028 (54.4%) patients were transferred. Of these, 528 (58.1%) had heart failure related CS (HF-CS) and 381 (41.9%) had CS related to acute myocardial infarction (AMI-CS). Upon arrival to the CSWG site, transfer patients were more likely to be in SCAI stage C and D, when compared to non-transfer patients. Transfer patients had higher mortality (37% vs. 29%, <0.001) than non-transfer patients with the differences primarily driven by the HF-CS cohort. Logistic regression identified increasing age, mechanical ventilation, renal replacement therapy, and higher number of vasoactive drugs prior to, or within 24 hours after CSWG site transfer as independent predictors of mortality among HF-CS patients. Conversely, pulmonary artery catheter use prior to transfer, or within 24 hours of arrival was associated with decreased mortality. Among transfer AMI-CS patients BMI>28 kg/m<sup>2</sup>, worsening renal failure, lactate>3 mg/dl and increasing number of vasoactive drugs were associated with increased mortality.<br /><b>Conclusion</b><br />More than half of CS patients managed at high volume CS centers were transferred from another hospital. Although transfer patients had higher mortality than those who were primarily admitted to hub centers, outcomes and their predictors varied significantly when classified by HF-CS versus AMI-CS.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 27 Sep 2023; epub ahead of print</small></div>

<div><h4>TEMPORARY REMOVAL: Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America.</h4><i>Bozkurt B, Ahmad T, Alexander K, Baker WL, ... Vaduganathan M, Ziaeian B</i><br /><AbstractText>The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.</AbstractText><br /><br />Copyright © 2023.<br /><br /><small>J Card Fail: 26 Sep 2023; epub ahead of print</small></div>

<div><h4>Development and Optimization of the Veterans Affairs\' National Heart Failure Dashboard for Population Health Management.</h4><i>Brownell N, Kay C, Parra D, Anderson S, ... Young E, Ziaeian B</i><br /><b>Background</b><br />In 2020, the Veterans\' Affairs (VA) healthcare system deployed a heart failure (HF) dashboard for use nationally. The initial version was notably imprecise and unreliable for the identification of HF subtypes. We describe the development and subsequent optimization of the VA national HF dashboard.<br /><b>Materials and methods</b><br />This study describes the stepwise process for improving the accuracy of the VA national HF dashboard, including defining the initial dashboard, improvement of case definitions, utilization of natural language processing for patient identification, and incorporation of an imaging quality hierarchy model. Optimization further included evaluating whether to require concurrent ICD-codes for inclusion in the dashboard and assessing various imaging modalities for patient characterization.<br /><b>Results</b><br />Through multiple rounds of optimization, the dashboard accuracy (defined as the proportion of true results to the total population) was improved from 54.1% to 89.2% for the identification of HF with reduced ejection fraction (HFrEF) and from 53.9% to 88.0% for the identification of HF with preserved ejection fraction (HFpEF). To align with current guidelines, HF with mildly reduced ejection fraction (HFmrEF) was added to the dashboard output with 88.0% accuracy.<br /><b>Conclusions</b><br />The inclusion of an imaging quality hierarchy model and natural language processing algorithm improved the accuracy of the VA national HF dashboard. The revised dashboard informatics algorithm has higher utilization rates and improved reliability for population health management.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 25 Sep 2023; epub ahead of print</small></div>

<div><h4>Medical Therapy Before, During, and After Hospitalization in Medicare Beneficiaries with Heart Failure and Diabetes: The Get With The Guidelines - Heart Failure Registry.</h4><i>Bhatt AS, Fonarow GC, Greene SJ, Holmes DN, ... Yancy CW, Vaduganathan M</i><br /><b>Background</b><br />Patients hospitalized with heart failure (HF) and diabetes mellitus (DM) are at risk for worsening clinical status. Little is known about the frequency of therapeutic changes during hospitalization. We characterized use of medical therapies before, during, and after hospitalization in patients with HF and DM.<br /><b>Methods</b><br />We identified Medicare beneficiaries in Get With The Guidelines®-Heart Failure (GWTG-HF) hospitalized between July 2014-September 2019 with Part D prescription coverage. We evaluated trends in the use of 7 classes of antihyperglycemic therapies (metformin, sulfonylureas, GLP-1RA, SGLT2-inhibitors, DPP-4 inhibitors, thiazolidinediones, and insulins) and 4 classes of HF therapies (evidence-based β-blockers, ACEi or ARB, MRA, and ARNI). Medication fills were assessed at 6 and 3 months before hospitalization, at hospital discharge, and 3 months post-discharge.<br /><b>Results</b><br />Among 35,165 Medicare beneficiaries, median age was 77 years, 54% were women, and 76% were White, 11,660 (33%) had HFrEF (LVEF≤40%), 3,700 (11%) had HFmrEF(LVEF 41-49%), and 19,805 (56%) had HFpEF (LVEF≥50%). Overall, insulin was the most prescribed antihyperglycemic after HF hospitalization (n=12,919, 37%), followed by metformin (n=7,460, 21%) and sulfonylureas (n= 7,030, 20%). GLP-1RA (n= 700, 2.0%) and SGLT2i (n=287, 1.0%) use was low and did not improve over time. In patients with HFrEF, evidence-based β-blocker, RASi, MRA, and ARNI fills 6 months preceding HF hospitalization were 63%, 62%, 19%, and 4%, respectively. Fills initially declined prior to hospitalization, but then rose from 3 months before hospitalization to discharge (β-blockers:56% to 82%, RASi: 51% to 57%, MRA: 15% to 28%, ARNI: 3% to 6%, triple therapy: 8% to 20%; P<0.01 for all). Prescription rates 3 months after hospitalization were similar to those at hospital discharge.<br /><b>Conclusions</b><br />In-hospital optimization of medical therapy in patients with HF and DM is common among participating hospitals.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 25 Sep 2023; epub ahead of print</small></div>

<div><h4>IV Diuresis in Alternative Treatment Settings for the Management of Heart Failure: Implications for Mortality, Hospitalizations, and Cost.</h4><i>Jiang GY, Lee C, Kearing SA, Wadhera RK, ... Wasfy JH, Zeitler EP</i><br /><b>Background</b><br />Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association between HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations, and cost.<br /><b>Methods</b><br />Using 100% Medicare inpatient, outpatient, and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified. Encounters were sorted into mutually exclusive settings: (1) inpatient; (2) observation; (3) ED; or (4) outpatient IV diuretic clinic. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day hospitalization and total 30-day costs. Multivariable logistic and linear regression were used to examine the association between treatment location and the primary and secondary outcomes.<br /><b>Results</b><br />Patients treated in observation and outpatient settings had lower 30-day mortality rates (Observation OR 0.67, 95% CI 0.66-0.69, p < 0.001; Outpatient OR 0.53, 95% CI 0.51-0.55, p < 0.001) compared to those treated in the inpatient setting. Observation and outpatient treatment were also associated with decreased 30-day total cost compared to inpatient treatment (Observation relative cost -$5,528.77, 95% CI $-$5,613.63 to -$5,443.92; Outpatient relative cost -$7,005.95; 95% CI -$7,103.94 to -$6,907.96). Patients treated in the ED and discharged had increased mortality (OR 1.15, 95% CI 1.13-1.17, p < 0.001) and increased rates of hospitalization (OR 1.72, 95% CI 1.70-1.73, p < 0.001) compared to patients treated as inpatients.<br /><b>Conclusions</b><br />Medicare beneficiaries who received IV diuresis for acute HF in the outpatient and observation settings had lower mortality and decreased cost of care compared to patients treated as inpatients. Outpatient and observation management of acute decompensated HF, when available, is a safe and cost-effective strategy in certain populations of patients with HF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 13 Sep 2023; epub ahead of print</small></div>

<div><h4>The Effect of Omecamtiv Mecarbil in Hospitalized Patients as Compared with Outpatients with HFrEF: an Analysis of GALACTIC-HF.</h4><i>Docherty KF, McMurray JJV, Diaz R, Felker GM, ... Malik FI, Teerlink JR</i><br /><b>Background</b><br />In the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF and reduced ejection fraction (HFrEF). The primary aim of this prespecified analysis was to evaluate the safety and efficacy of omecamtiv mecarbil by randomization setting i.e., whether participants were enrolled as outpatients or inpatients.<br /><b>Methods and results</b><br />Patients were randomized either during a HF hospitalization or as an outpatient, within one year of a worsening HF event (hospitalization or emergency department [ED] visit). The primary outcome was a composite of worsening HF event (HF hospitalization or an urgent ED or clinic visit) or cardiovascular death. Of the 8232 patients analyzed, 2084 (25%) were hospitalized at randomization. Hospitalized patients had higher NT-proBNP concentrations, lower systolic blood pressure, reported more symptoms and were less frequently treated with a renin-angiotensin system blocker or a beta-blocker than outpatients. The rate (per 100 person-years [PY]) of the primary outcome was higher in hospitalized patients (placebo group=38.3/100 PY) than in outpatients (23.1/100 PY); adjusted hazard ratio (HR) 1.21 (95%CI 1.12, 1.31). The effect of omecamtiv mecarbil versus placebo on the primary outcome was similar in hospitalized patients (HR 0.89, 95%CI 0.78, 1.01) and outpatients (HR 0.94, 95%CI 0.86, 1.02) (interaction P=0.51).<br /><b>Conclusion</b><br />Hospitalized HFrEF patients had a higher rate of the primary outcome than outpatients. Omecamtiv mecarbil reduced the risk of the primary outcome both when initiated in hospitalized patients and in outpatients.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 06 Sep 2023; epub ahead of print</small></div>

<div><h4>Early initiation of sacubitril/valsartan in patients with acute heart failure and renal dysfunction: An analysis of the TRANSITION study.</h4><i>Straburzynska-Migaj E, Senni M, Wachter R, Fonseca C, ... Pascual-Figal D, TRANSITION Investigators</i><br /><b>Background</b><br />Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging due to the risk of further deterioration in renal function, especially after acute decompensated heart failure (ADHF).<br /><b>Methods and results</b><br />We assessed the effect of RD (eGFR ≥30-<60 mL/min/1.73 m<sup>2</sup>) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized HFrEF patients admitted for ADHF (RD, n=476; non-RD, n=483). At Week 10, target dose of sacubitril/valsartan (97/103 mg bid) was achieved by 42% patients in RD subgroup versus 54% in non-RD (P<0.001). Sacubitril/valsartan was associated with greater eGFR improvements in RD subgroup than non-RD (change from baseline LSM, 4.1 mL/min/1.73 m<sup>2</sup>; 95% CI 2.2-6.1; P<0.001). Cardiac biomarkers improved significantly in both subgroups; however, compared to RD subgroup the improvement was greater in those without RD (NT-proBNP: -28.6% vs -44.8%; hsTnT: -20.3% vs -33.9%) (P<0.001). Patients in RD subgroup compared to those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%; P<0.001), investigator-reported cardiac failure (9.7% vs 5.6%; P=0.029), and renal impairment (6.4% vs 2.1%; P=0.002).<br /><b>Conclusions</b><br />Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in eGFR and cardiac biomarkers.<br /><b>Clinical trial registration</b><br />NCT02661217.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 05 Sep 2023; epub ahead of print</small></div>

<div><h4>Peripheral Venous Pressure Measurements to Evaluate Congestion in Heart Failure.</h4><i>Maruichi-Kawakami S, Nagao K, Aida K, Matsuto K, ... Kimura T, Inada T</i><br /><b>Background</b><br />Accurate bedside assessment of congestion in the management of patients with heart failure remains challenging. As a continuous conduit of circulating fluid, systemic congestion represented by high right atrial pressure (RAP) may be reflected by peripheral venous pressure (PVP). We evaluated the reliability of PVP measurements for assessing congestion beyond conventional clinical assessments.<br /><b>Methods and results</b><br />We performed conventional congestion assessments and PVP measurements in 95 patients undergoing pulmonary artery catheterization. PVP was measured via the 22-gauge peripheral venous access placed in the upper extremity. The median RAP and PVP was 7 (interquartile range [IQR]: 5-11) mmHg and 9 (IQR: 7-12) mmHg, respectively, with a mean bias of 1.8 ± 2.6 mmHg. PVP exhibited a strong linear correlation with RAP (Spearman R = 0.81; P < 0.001). PVP demonstrated greater discriminatory power for both RAP ≤ 8 mmHg (area under the curve [AUC]: 0.91 [95% confidence interval: 0.85-0.97]; sensitivity: 75%; specificity: 87%) and RAP > 12 mmHg (AUC: 0.98 [0.95-1.00]; sensitivity: 88%; specificity: 95%) than edema, jugular venous pressure, pulmonary congestion on chest radiograph, B-type natriuretic peptide levels, and inferior vena cava diameter.<br /><b>Conclusions</b><br />PVP measured via peripheral venous access strongly correlates with invasively obtained RAP. PVP measurements may improve current bedside assessments of congestion.<br /><br />Copyright © 2021 Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 01 Sep 2023; 29:1319-1323</small></div>

<div><h4>LMNA Cardiomyopathy: Important Considerations for the Heart Failure Clinician.</h4><i>Rosario KF, Karra R, Amos K, Landstrom A, ... Kim H, DeVore AD</i><br /><b>Importance</b><br />A diagnosis of LMNA cardiomyopathy not only impacts disease prognosis but also leads to specific guideline-recommended treatment options for these patients. This is fundamentally different from other genetic causes of dilated cardiomyopathy.<br /><b>Observations</b><br />LMNA cardiomyopathy often presents early in the third to fourth decade and there is an age-dependent penetrance of nearly 90% among those with a positive genotype for LMNA cardiomyopathy. Oftentimes, electrical abnormalities with either conduction disturbances and/or either atrial or ventricular arrhythmias manifest before there is imaging evidence of left ventricular dysfunction. Given these subtle early findings, cardiac magnetic resonance imaging provides helpful guidance regarding patterns of enhancement associated with LMNA cardiomyopathy, often before there is significant left ventricular dilation and/or a drop in ejection fraction and could be used for further understanding of risk stratification and prognosis of asymptomatic genotype-positive individuals. Among symptomatic patients with LMNA-CM, about a quarter of individuals progress to needing advanced heart failure therapies such as heart transplantation.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In the era of precision medicine, increased recognition of clinical findings associated with LMNA cardiomyopathy and increased detection by genetic testing among patients with \'idiopathic\' non-ischemic cardiomyopathy is of increasing importance. Not only does a diagnosis of LMNA cardiomyopathy have implications for management and risk stratification, but new gene-based therapies continue to be evaluated for this group. Clinicians must be aware not only of the general indications for genetic testing in arrhythmogenic and dilated cardiomyopathies and of when to suspect LMNA cardiomyopathy, but also of the clinical trials underway targeted towards the different genetic cardiomyopathies.<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 31 Aug 2023; epub ahead of print</small></div>