<div><h4>Efficacy of Sotagliflozin in Adults With Type 2 Diabetes in Relation to Baseline Hemoglobin A1c.</h4><i>Aggarwal R, Bhatt DL, Szarek M, Cannon CP, ... Pitt B, Steg PG</i><br /><b>Background</b><br />The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease.<br /><b>Objectives</b><br />We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels.<br /><b>Methods</b><br />We included all adults from SCORED and SOLOIST-WHF. The primary outcome was a composite of cardiovascular death, hospitalizations for HF, and urgent visits for HF. The efficacy of sotagliflozin compared with placebo was evaluated by baseline HbA1c using competing-risk marginal proportional hazards models.<br /><b>Results</b><br />We identified 11,744 adults. Individuals with HbA1c ≤7.5% experienced the primary outcome at a lower rate in the sotagliflozin group (11.2 per 100 person-years) than the placebo group (15.5 per 100 person-years) (HR: 0.73; 95% CI: 0.57-0.93). Similarly, individuals with HbA1c of 7.6% to 9.0% experienced the primary outcome at a lower rate in the sotagliflozin group (7.3 per 100 person-years) than the placebo group (9.4 per 100 person-years) (HR: 0.77; 95% CI: 0.63-0.96). These findings were also consistent among individuals with HbA1c >9.0%, with a primary outcome rate in the sotagliflozin group (7.8 per 100 person-years) that was lower than the placebo group (11.6 per 100 person-years) (HR: 0.65; 95% CI: 0.50-0.84). The efficacy of sotagliflozin was consistent by baseline HbA1c level (P for interaction = 0.58).<br /><b>Conclusions</b><br />In individuals with type 2 diabetes and either HF or kidney disease, sotagliflozin reduced HF outcomes irrespective of baseline HbA1c.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Nov 2023; 82:1842-1851</small></div>

<div><h4>Guideline directed medical therapy in severe heart failure with reduced ejection fraction: an analysis from the HELP-HF Registry.</h4><i>Tomasoni D, Pagnesi M, Colombo G, Chiarito M, ... Savarese G, Metra M</i><br /><b>Background</b><br />Persistent symptoms despite guideline directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking.<br /><b>Methods and results</b><br />We included 699 consecutive patients with HFrEF and at least one \"I NEED HELP\" marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonist (MRA). Overall, ≥50% of target doses were reached in 41%, 22% and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41% and 55% for BB, ACEi/ARB/ARNI and MRA, respectively).The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR], 0.63, 95% confidence interval [CI], 0.48-0.84, and HR 0.74, 95%CI 0.58-0.95, respectively).<br /><b>Conclusions</b><br />In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were under-treated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity. 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: 07 Nov 2023; epub ahead of print</small></div>

<div><h4>Association Between the Liver Fibrosis Markers and Scores, and Hemodynamic Congestion Assessed by Peripheral Venous Pressure in Patients With Acute Heart Failure.</h4><i>Nagao K, Maruichi-Kawakami S, Aida K, Matsuto K, ... Hayashi F, Inada T</i><br /><AbstractText><br /><b>Background:</b><br/>Peripheral venous pressure (PVP) has been shown to be a reliable surrogate for right atrial pressure in assessing congestion in patients with heart failure (HF). Liver fibrosis markers and scores can be useful in assessing organ injury in patients with acute HF. This study aimed to investigate the association of liver fibrosis markers and scores with PVP in patients with acute HF. Methods and Results The 7S domain of the collagen type IV N-terminal propeptide (P4NP 7S), aspartate aminotransferase-to-platelet ratio index, fibrosis-4, and nonalcoholic fatty liver disease fibrosis score were determined along with PVP measurements before discharge in 229 patients with acute HF. The strongest correlation with PVP was found for P4NP 7S (Pearson <i>r</i>=0.40). Patients with high P4NP 7S levels (≥median [6.2 ng/mL]) had an increased risk of cardiovascular death or HF hospitalization (adjusted hazard ratio [HR], 1.80 [95% CI, 1.09-3.04], <i>P</i>=0.02). The concomitant high PVP (≥mean [8 mm Hg])/high P4NP 7S group, in contrast to the high PVP/low P4NP 7S or low PVP/high P4NP 7S group, had a significant risk relative to the low PVP/low P4NP 7S group for cardiovascular death or HF hospitalization (adjusted HR, 2.63 [95% CI, 1.43-5.05], <i>P</i>=0.002). A sustained elevation in PVP for 1 month postdischarge was associated with a persistent increase in P4NP 7S. <br /><b>Conclusions:</b><br/>The study demonstrated the relationship between the liver fibrosis marker P4NP 7S and congestion. PVP and P4NP 7S could be useful for assessing congestion-related organ injury and predicting prognosis in patients with acute HF.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 07 Nov 2023; 12:e030788</small></div>

<div><h4>Temporal Trends in Heart Failure Management and Outcomes: Insights From a Japanese Multicenter Registry of Tertiary Care Centers.</h4><i>Nakamaru R, Kohsaka S, Shiraishi Y, Kohno T, ... Mizuno A, Yoshikawa T</i><br /><AbstractText><br /><b>Background:</b><br/>The management of heart failure (HF) has markedly changed, due to changes in demographics and the emergence of novel pharmacotherapies. However, detailed analyses on the temporal trends in characteristics and outcomes among patients with HF are scarcely available. This study aimed to assess the temporal trends over 11 years in clinical management and outcomes in patients with HF. Methods and Results We analyzed data from a multicenter registry of hospitalized patients with acute HF, including 6877 patients registered from 2011 to 2021. Age-adjusted mortality was calculated using standardized mortality ratios. During the study period, mean age increased from 75.2 years in 2011 to 2012 to 76.4 years in 2020 to 2021 (<i>P</i> for trend <0.001). The proportion of HF with reduced ejection fraction (HFrEF, left ventricular ejection fraction <40%) remained constant (from 43.4% to 42.7%, <i>P</i> for trend=0.38). The median duration of hospital stays (from 15 to 17 days, <i>P</i> for trend<0.001) had increased. As for the implementation of guideline-directed medical therapy, the use of mineralocorticoid receptor antagonist at discharge increased in patients with HFrEF (from 44.3% to 60.2%, <i>P</i> for trend<0.001). There was also an increase in the use of sodium-glucose cotransporter-2 inhibitors following their approval for use. The age-adjusted 1-year mortality decreased in patients with HFrEF (from 18.0% to 9.3%, <i>P</i> for trend<0.001) but not in patients with non-HFrEF (left ventricular ejection fraction ≥40%; from 9.2% to 9.5%, <i>P</i> for trend=0.79). <br /><b>Conclusions:</b><br/>Hospitalized patients with HF have been aging over the past decade. Their long-term outcomes after discharge have improved predominantly because of decreased mortality in patients with HFrEF.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 07 Nov 2023; 12:e031179</small></div>

<div><h4>Patient Awareness of Heart Failure Diagnosis: A Community Study.</h4><i>Shropshire SJ, Fabbri M, Manemann SM, Roger VL, ... Weston SA, Chamberlain AM</i><br /><AbstractText><br /><b>Background:</b><br/>Heart failure (HF) is a complex disease that contributes to a high number of hospitalizations, deaths, and economic health care costs each year. However, among patients with HF, there is a lack of awareness of their HF diagnosis that has not been fully examined. Methods and Results Residents from 3 counties of southeast Minnesota with a first-ever <i>International Classification of Diseases, Ninth Revision</i> (<i>ICD-9</i>) code 428 or <i>Tenth Revision</i> (<i>ICD-10</i>) code I50 between January 1, 2013 and March 31, 2016 (N=2461) were prospectively surveyed to measure HF self-awareness. A total of 1114 patients returned the survey (response rate, 45%), and 787 had validated HF upon medical record review. Among these 787 patients with HF (mean age, 76 years; 53% men), 37% (n=293) were aware of their HF diagnosis. After adjustment, being a woman (odds ratio [OR], 1.56 [95% CI, 1.10-2.22]), having HF with reduced ejection fraction (OR, 1.58 [95% CI, 1.13-2.22]), attending the HF clinic (OR, 4.07 [95% CI, 2.25-7.36]), and having coronary artery disease (OR, 1.65 [95% CI, 1.16-2.37]) were all associated with increased awareness of an HF diagnosis. Conversely, having diabetes was associated with decreased awareness of an HF diagnosis (adjusted OR, 0.69 [95% CI, 0.50-0.95]). <br /><b>Conclusions:</b><br/>Awareness of an HF diagnosis is low in a community population of patients with HF. Strategies to improve patient awareness of their diagnosis should be implemented to improve self-care behaviors and outcomes in patients with HF.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 07 Nov 2023; 12:e029284</small></div>

<div><h4>An Economic Modeling Analysis of an Intensive GDMT Optimization Program in Hospitalized Heart Failure Patients.</h4><i>Dixit NM, Parikh NU, Ziaeian B, Fonarow GC</i><br /><AbstractText><b>Background:</b> The STRONG-HF trial demonstrated substantial reductions in the composite of mortality and morbidity over 6 months among hospitalized heart failure patients who were randomized to intensive guideline-directed medical therapy (GDMT) optimization compared to usual care. Whether an intensive GDMT optimization program would be cost-effective for patients with heart failure with reduced ejection fraction (HFrEF) is unknown. <br /><b>Methods:</b><br/>Using a 2-state Markov model we evaluated the effect of an intensive GDMT optimization program on hospitalized patients with HFrEF. Two population models were created to simulate this intervention, a \"Clinical Trial\" model, based off the participants in the STRONG-HF trial and a \"Real-World\" model, based off the Get With The Guidelines-HF Registry of patients admitted with worsening HF. We then modeled the effect of a 6-month intensive triple therapy GDMT optimization program comprised of cardiologists, clinical pharmacists, and registered nurses. Hazard ratios from the intervention arm of the STRONG-HF trial were applied to both populations models to simulate clinical and financial outcomes of an intensive GDMT optimization program from a United States healthcare sector perspective with a lifetime time horizon. Optimal quadruple GDMT use was also modeled. <br /><b>Results:</b><br/>An intensive GDMT optimization program was extremely cost-effective with incremental cost-effectiveness ratios <$10,000 per quality-adjusted life year in both models. Optimal quadruple GDMT implementation resulted in the most gains in life years with incremental cost-effectiveness ratios of $60,000 and $54,000 in the Clinical Trial and Real-World models, respectively. <b>Conclusions:</b> An intensive GDMT optimization program for patients hospitalized with HFrEF would be cost-effective and result in substantial gains in clinical outcomes especially with use of optimal quadruple GDMT. Clinicians, payers, and policy makers should prioritize creation of such programs.</AbstractText><br /><br /><br /><br /><small>Circ Heart Fail: 06 Nov 2023; epub ahead of print</small></div>

<div><h4>Sacubitril/valsartan compared to ramipril in high-risk post myocardial infarction patients stratified according use of mineralocorticoid receptor antagonists: Insight from PARADISE MI trial.</h4><i>Schou M, Claggett B, Miao ZM, Fernandez A, ... Pfeffer MA, Køber L</i><br /><b>Background</b><br />It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (ARNI) is affected by Mineralocorticoid receptor antagonists (MRA) in high-risk myocardial infarction (MI) patients.<br /><b>Purpose</b><br />To examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion.<br /><b>Methods</b><br />Patients (N=5661) included in the PARADISE MI Trial (Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure (HF) Events after MI) were stratified according to MRA. Primary outcomes in this substudy were worsening HF or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalemia > 5.5 mmol/L or permanent drug discontinuation.<br /><b>Results</b><br />2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by +/-MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalemia or permanent drug discontinuation was not significantly altered by ARNI (P> 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA: hazard ratio<sub>MRA</sub> : (95% confidence interval [CI]): 0.96 (0.77, 1.19) versus (HR<sub>MRA-</sub> 0.87 (95% CI: 0.71, 1.05), respectively, for the primary endpoint (p value for interaction = 0.51) (CEC adjudicated); similar findings were observed if investigator reported endpoints were evaluated (P = 0.61 for interaction).<br /><b>Conclusions</b><br />Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post MI setting in patients with LVSD and/or congestion. 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: 06 Nov 2023; epub ahead of print</small></div>

<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>Detailed Assessment of the \"I Need Help\" Criteria in Patients With Heart Failure: Insights From the HELP-HF Registry.</h4><i>Pagnesi M, Ghiraldin D, Vizzardi E, Chiarito M, ... Pini D, Metra M</i><br /><b>Background</b><br />The \"I Need Help\" markers have been proposed to identify patients with advanced heart failure (HF). We evaluated the prognostic impact of these markers on clinical outcomes in a real-world, contemporary, multicenter HF population.<br /><b>Methods</b><br />We included consecutive patients with HF and at least 1 high-risk \"I Need Help\" marker from 4 centers. The impact of the cumulative number of \"I Need Help\" criteria and that of each individual \"I Need Help\" criterion was evaluated. The primary end point was the composite of all-cause mortality or first HF hospitalization.<br /><b>Results</b><br />Among 1149 patients enrolled, the majority had 2 (30.9%) or 3 (22.6%) \"I Need Help\" criteria. A higher cumulative number of \"I Need Help\" criteria was independently associated with a higher risk of the primary end point (adjusted hazard ratio for each criterion increase, 1.19 [95% CI, 1.11-1.27]; <i>P</i><0.001), and patients with >5 criteria had the worst prognosis. Need of inotropes, persistently high New York Heart Association classes III and IV or natriuretic peptides, end-organ dysfunction, >1 HF hospitalization in the last year, persisting fluid overload or escalating diuretics, and low blood pressure were the individual criteria independently associated with a higher risk of the primary end point.<br /><b>Conclusions</b><br />In our HF population, a higher number of \"I Need Help\" criteria was associated with a worse prognosis. The individual criteria with an independent impact on mortality or HF hospitalization were need of inotropes, New York Heart Association class or natriuretic peptides, end-organ dysfunction, multiple HF hospitalizations, persisting edema or escalating diuretics, and low blood pressure.<br /><br /><br /><br /><small>Circ Heart Fail: 01 Nov 2023:e011003; epub ahead of print</small></div>

<div><h4>Telehealth and Health Equity in Older Adults With Heart Failure: A Scientific Statement From the American Heart Association.</h4><i>Masterson Creber R, Dodson JA, Bidwell J, Breathett K, ... Kitsiou S, American Heart Association Cardiovascular Disease in Older Populations Committee of the Council on Clinical Cardiology and the Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Council on Peripheral Vascular Disease</i><br /><AbstractText>Enhancing access to care using telehealth is a priority for improving outcomes among older adults with heart failure, increasing quality of care, and decreasing costs. Telehealth has the potential to increase access to care for patients who live in underresourced geographic regions, have physical disabilities or poor access to transportation, and may not otherwise have access to cardiologists with expertise in heart failure. During the COVID-19 pandemic, access to telehealth expanded, and yet barriers to access, including broadband inequality, low digital literacy, and structural barriers, prevented many of the disadvantaged patients from getting equitable access. Using a health equity lens, this scientific statement reviews the literature on telehealth for older adults with heart failure; provides an overview of structural, organizational, and personal barriers to telehealth; and presents novel interventions that pair telemedicine with in-person services to mitigate existing barriers and structural inequities.</AbstractText><br /><br /><br /><br /><small>Circ Cardiovasc Qual Outcomes: 01 Nov 2023:e000123; epub ahead of print</small></div>

<div><h4>Disturbance in bodily experience following ventricular assist device implantation.</h4><i>Richter F, Spielmann H, Semmig-Koenze S, Spitz-Köberich C, ... Tigges-Limmer K, Albert W</i><br /><b>Background</b><br />Disturbance in bodily experience (BE) is a potential adverse consequence of ventricular assist device (VAD) implantation. The concept BE encompasses all cognitive and affective processes related to the subjective experience of one\'s own body.<br /><b>Methods</b><br />A cross-sectional, multi-center study was performed, involving 365 VAD patients (85 % male; time post-implant: 3 - 36 months). Patients completed a BE questionnaire (BE-S, 5-point Likert scale), and the disturbance in BE was analyzed based on sex, time since implantation (in the first, second or third year post implant), and patient acuity (elective vs. emergent implantation). Subsidiary, patients\' gratitude was surveyed.<br /><b>Results</b><br />Disturbance in BE was not particularly pronounced (M = 2.69, SD = 1.17). 85 % of patients expressed high levels of gratitude. Disturbance in BE decreased (p =.04), while gratitude increased (p =.02) with time since implantation. Female patients showed more disturbance in BE (p =.01) and less gratitude (p =.01) compared to male patients. Among patients who underwent emergency implantation, the decrease in disturbance occurred predominantly in the third year, exceeding the level observed in elective implanted patients (p =.03).<br /><b>Conclusions</b><br />Disturbance in BE following VAD implantation does generally not reach excessive levels and tends to decrease over time. Our data indicate more disturbance and less gratitude in female patients. In emergently implanted patients, disturbance in BE is prolonged. Screening for disturbance in BE is recommended during follow-up, especially for these at-risk groups, to ensure early and focused psychological support.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 01 Nov 2023; epub ahead of print</small></div>

<div><h4>Impact of Female Sex on Cardiogenic Shock Outcomes: A Cardiogenic Shock Working Group Report.</h4><i>Ton VK, Kanwar MK, Li B, Blumer V, ... Burkhoff D, Kapur NK</i><br /><b>Background</b><br />Studies reporting cardiogenic shock (CS) outcomes in women are scarce.<br /><b>Objectives</b><br />The authors compared survival at discharge among women vs men with CS complicating acute myocardial infarction (AMI-CS) and heart failure (HF-CS).<br /><b>Methods</b><br />The authors analyzed 5,083 CS patients in the Cardiogenic Shock Working Group. Propensity score matching (PSM) was performed with the use of baseline characteristics. Logistic regression was performed for log odds of survival.<br /><b>Results</b><br />Among 5,083 patients, 1,522 were women (30%), whose mean age was 61.8 ± 15.8 years. There were 30% women and 29.1% men with AMI-CS (P = 0.03). More women presented with de novo HF-CS compared with men (26.2% vs 19.3%; P < 0.001). Before PSM, differences in baseline characteristics and sex-specific outcomes were seen in the HF-CS cohort, with worse survival at discharge (69.9% vs 74.4%; P = 0.009) and a higher rate of maximum Society for Cardiac Angiography and Interventions stage E (26% vs 21%; P = 0.04) in women than in men. Women were less likely to receive pulmonary artery catheterization (52.9% vs 54.6%; P < 0.001), heart transplantation (6.5% vs 10.3%; P < 0.001), or left ventricular assist device implantation (7.8% vs 10%; P = 0.01). Regardless of CS etiology, women had more vascular complications (8.8% vs 5.7%; P < 0.001), bleeding (7.1% vs 5.2%; P = 0.01), and limb ischemia (6.8% vs 4.5%; P = 0.001). More vascular complications persisted in women after PSM (10.4% women vs 7.4% men; P = 0.06).<br /><b>Conclusions</b><br />Women with HF-CS had worse outcomes and more vascular complications than men with HF-CS. More studies are needed to identify barriers to advanced therapies, decrease complications, and improve outcomes of women with CS.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 01 Nov 2023; epub ahead of print</small></div>

<div><h4>Clinical, Echocardiographic, and Longitudinal Characteristics Associated with Heart Failure with Improved Ejection Fraction.</h4><i>Romero E, Baltodano AF, Rocha P, Sellers-Porter C, ... Lopez JE, Cadeiras M</i><br /><AbstractText>Heart failure (HF) with improved ejection fraction (HFimpEF) has better outcomes than HF with reduced ejection fraction (HFrEF). However, factors contributing to HFimpEF remain unclear. This study aimed to evaluate clinical and longitudinal characteristics associated with subsequent HFimpEF. This was a single-center retrospective HFrEF cohort study. Data were collected from 2014 to 2022. Patients with HFrEF were identified using ICD codes, echocardiographic data, and natriuretic peptide levels. The main endpoints were HFimpEF (defined as ejection fraction >40% at ≥3 months with ≥10% increase) and mortality. Cox proportional hazards and mixed effects models were used for analyses. The study included 1307 HFrEF patients with a median follow-up of 16.3 months (IQR 8.0-30.6). The median age was 65 years; 68% were male while 57% were white. On follow-up, 38.7% (n=506) developed HFimpEF, while 61.3% (n=801) had persistent HFrEF. A multivariate Cox regression model identified sex, race comorbidities, echocardiographic, and natriuretic peptide as significant covariates of HFimpEF (p<0.05). The HFimpEF group had better survival compared to the persistent HFrEF group (p<0.001). Echocardiographic and laboratory trajectories differed between groups. In this HFrEF cohort, 38.7% transitioned to HFimpEF and approximately 50% met the definition within the first 12 months. In a HFimpEF model, sex, comorbidities, echocardiographic parameters, and natriuretic peptide were associated with subsequent HFimpEF. The model has the potential to identify patients at risk of subsequent persistent or improved HFrEF, thus informing the design and implementation of targeted quality-of-care improvement interventions.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am J Cardiol: 01 Nov 2023; epub ahead of print</small></div>

<div><h4>The short-term effects of sacubitril/valsartan therapy on myocardial oxygen consumption and energetic efficiency of cardiac work in heart failure with reduced ejection fraction. A randomized controlled study.</h4><i>Nesterov SV, Räty J, Nammas W, Maaniitty T, ... Saraste A, Knuuti J</i><br /><b>Aims</b><br />We sought to evaluate the mechanism of angiotensin-converting enzyme inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in HFrEF patients.<br /><b>Methods and results</b><br />The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with NYHA class II-III heart failure (HF) and left ventricular (LV) ejection fraction (EF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg BID or 160 mg BID) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic hemodynamics were quantified using echocardiography and <sup>11</sup> C-acetate PET before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group-27 patients, age 63±10 years, EF 29.2±10.4%, and valsartan only control group-28 patients, age 64±8 years, EF 29.0±7.3%, all ns.) The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both the diastolic (-4.5 mm Hg; p=0.026) and systolic blood pressure (-9.8 mm Hg; p=0.0007), myocardial perfusion (-0.054 mL/g/min; p=0.045), and LV mechanical work (-296; p=0.038) decreased significantly in the ARNI group compared with the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between treatment group difference was not significant (p=0.088).<br /><b>Conclusions</b><br />We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have hemodynamic and cardiac mechanical effects over valsartan in patients with HF. (EudraCT 2017-002113-64) 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: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Long-term outcome after upgrade to cardiac resynchronization therapy: A propensity score-matched analysis.</h4><i>Trenson S, Voros G, Martens P, Ingelaere S, ... Winnik S, Vandenberk B</i><br /><b>Background</b><br />Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long-term outcome after upgrade to CRT are scarce.<br /><b>Methods</b><br />International, multicenter retrospective registry including 2275 patients who underwent a de novo or upgrade CRT implantation and mean follow-up of 3.6±2.7 years. The primary composite endpoint included all-cause mortality, heart transplantation or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matched (PSM) analyses were performed.<br /><b>Results</b><br />Patients who underwent CRT upgrade (n=605, 26.6%) were less likely female (19.7% vs 28.8%, p<0.001), more often had ischemic cardiomyopathy (49.8% vs 40.2%, p<0.001), and had worse renal function (median eGFR 50.3 mL/m<sup>2</sup> (35.8-69.5) vs 59.9 mL/m<sup>2</sup> (43.0-76.5), p<0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade vs. 7.1%/year for de novo implantations (p<0.001). PSM for the primary endpoint resulted in 488 pairs. After PSM, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable HR 1.35, 95% CI 1.08-1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03-1.70) and ICD (multivariable HR 1.40, 95% CI 1.01-1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26-2.41).<br /><b>Conclusion</b><br />In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations. 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: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Early changes in renal function during rapid uptitration of guideline directed medical therapy following an admission for acute heart failure.</h4><i>Ter Maaten JM, Mebazaa A, Davison B, Edwards C, ... Cotter G, Voors AA</i><br /><b>Introduction</b><br />In this subgroup analysis of STRONG-HF we explored the association between changes in renal function and efficacy of rapid up-titration of guideline directed medical therapy (GDMT) according to a high intensity care (HIC) strategy.<br /><b>Methods</b><br />In patients randomized to the HIC arm (n = 542), renal function was assessed at baseline and during follow-up visits. We studied the association with clinical characteristics and outcomes of a decrease in estimated glomerular filtration rate (eGFR) at week 1, defined as ≥15% decrease from baseline. Patients in the usual care group (n = 536) were seen at day 90.<br /><b>Results</b><br />The treatment effect of HIC versus usual care was independent of baseline eGFR (P-interaction: 0.4809). A decrease in eGFR within 1 week occurred in 77 (15.5%) patients and was associated with more rales on examination (P = 0.004), and a higher NYHA class at the corresponding visit. Following the decrease in eGFR at 1 week, lower average optimal doses of GDMT were prescribed during follow-up (P = 0.0210) and smaller reductions in NT-proBNP occurred (geometrical mean 0.81 in no eGFR decrease vs 1.12 in GFR decrease, P = 0.0003). The rate of HF readmission or death at 180 days was 12.3% in no eGFR decrease vs. 18.5% in eGFR decrease (P = 0.2274) and HF readmissions were 7.8% vs 16.6% respectively, P = 0.0496.<br /><b>Conclusions</b><br />In the STRONG-HF study, HIC reduced 180-day HF readmission or death regardless of baseline eGFR. An early decrease in eGFR during rapid uptitration of GDMT was associated with more evidence of congestion yet lower doses of GDMT during follow-up. 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: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies.</h4><i>Polovina M, Tschöpe C, Rosano G, Metra M, ... Coats AJ, Seferović PM</i><br /><AbstractText>Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15%-0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age- and sex-matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better-informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in-depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non-dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarises established and emerging risk factors for life-threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence-based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification. This article is protected by copyright. All rights reserved.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Interaction of Heart Failure and Stroke: A clinical consensus statement of the ESC Council on Stroke, the Heart Failure Association (HFA) and the ESC Working Group on Thrombosis.</h4><i>Doehner W, Böhm M, Boriani G, Christersson C, ... Vilahur G, Rosano G</i><br /><AbstractText>Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi-directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and - in turn - acute cerebral injury via imbalanced neural and neurovegetative control of cardiovascular regulation may induce or aggravate HF. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiologic interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiologic mechanisms, complications clinical management in acute conditions and in long-term care of patients with the comorbidity are presented and state of the art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long-term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of heart failure and stroke.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Characteristics and outcomes of patients with atrial versus ventricular secondary tricuspid regurgitation undergoing tricuspid transcatheter edge-to-edge repair - Results from TriValve Registry.</h4><i>Russo G, Badano LP, Adamo M, Alessandrini H, ... Metra M, Taramasso M</i><br /><b>Background</b><br />Secondary or functional tricuspid regurgitation (STR) is the most common phenotype of tricuspid regurgitation (TR) with atrial STR (ASTR) and ventricular STR (VSTR) being recently identified as two distinct entities. Data on tricuspid transcatheter edge-to-edge repair (T-TEER) in patients with STR according to phenotype (i.e. ASTR vs VSTR) are lacking.<br /><b>Objectives</b><br />The aim of this study was to assess characteristics and outcomes of patients with ASTR vs VSTR undergoing T-TEER.<br /><b>Methods</b><br />Patients with STR undergoing T-TEER were selected from the TriValve (Transcatheter Tricuspid Valve Therapies) registry. ASTR was defined by 1) left ventricular ejection fraction ≥50%; 2) atrial fibrillation and 3) systolic pulmonary arterial pressure < 50 mmHg. Patients not matching these criteria were classified as VSTR. Patients with primary TR and cardiac implantable electronic device were excluded. Key end-points included procedural success and survival at follow-up.<br /><b>Results</b><br />Two-hundred-ninety-eight patients were enrolled in the study: 65 (22%) with ASTR and 233 (78%) with VSTR. Procedural success was similar in the two groups (80% vs 83% for ASTR and VSTR, respectively, p = 0.56) and TEER was effective in reducing TR in both groups (from 97% of patients with baseline TR ≥3+ to 23% in ASTR and to 15% in VSTR, all p = 0.001). At 12 months follow-up, survival was significantly higher in ASTR vs VSTR cohort (91% vs 72%, log rank p = 0.02), with VSTR being an independent predictor of mortality at multivariable analysis (hazard ratio 4.75).<br /><b>Conclusions</b><br />In a real-world, multicenter registry, T-TEER was effective in reducing TR grade in both ASTR and VSTR. At 12-months follow-up, ASTR showed better survival than VSTR. This article is protected by copyright. All rights reserved.<br /><br />© 2023 European Society of Cardiology.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study.</h4><i>Lee HJ, Kim HK, Kim BS, Han KD, ... Lee H, Kim YJ</i><br /><b>Background</b><br />Sacubitril acts to inhibit neprilysin and as neprilysin is involved in amyloid-beta degradation in the central nervous system, and there is concern that sacubitril/valsartan may increase the risk of dementia. We aimed to compare the risk of incident dementia associated with sacubitril/valsartan and angiotensin II receptor blockers (ARBs).<br /><b>Methods</b><br />Patients with heart failure with reduced ejection fraction treated with either sacubitril/valsartan or ARB, identified from the Korean National Health Insurance Service database, were matched in a 1:2 ratio using propensity scores (6789 on sacubitril/valsartan and 13,578 on ARBs) and followed up for incident dementia.<br /><b>Results</b><br />During a mean follow-up of 2.5 years, 526 (2.6%) patients were newly diagnosed with dementia: Alzheimer dementia in 282, vascular dementia in 8, and other dementia in 236. There was no significant difference in the risk of overall dementia (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.70-1.01), Alzheimer dementia (HR 0.85, 95% CI 0.67-1.10), vascular dementia (HR 0.98, 95% CI 0.23-4.11), and all other dementias (HR 0.81, 95% CI 0.62-1.07) between sacubitril/valsartan users and ARB users. These results were consistent regardless of initial sacubitril/valsartan dose and subgroups including old age, previous mild cognitive impairment, previous stroke, and concomitant antiplatelet or anticoagulation. Sensitivity analysis with a 1-year lag period for dementia assessment confirmed the main analysis. Meanwhile, risk of incident stroke was lower in sacubitril/valsartan users compared to ARBs users.<br /><b>Conclusions</b><br />In a nationwide propensity-matched cohort of patients with heart failure, sacubitril/valsartan was not associated with an increased risk of incident dementia compared to ARBs. Sacubitril/valsartan and the risk of incident dementia in heart failure. ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor.<br /><br />© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.<br /><br /><small>Clin Res Cardiol: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Hypothermic oxygenated perfusion (HOPE) safely and effectively extends acceptable donor heart preservation times - results of the Australian and New Zealand trial.</h4><i>McGiffin DC, Kure CE, Macdonald PS, Jansz PC, ... Fraser JF, Kaye DM</i><br /><b>Background</b><br />Cold static storage (CSS) preservation of donor hearts for periods longer than 4 hours increases the risk of primary graft dysfunction (PGD). The aim of the study was to determine if hypothermic oxygenated perfusion (HOPE) could safely prolong the preservation time of donor hearts.<br /><b>Methods</b><br />We conducted a non-randomised, single arm, multi-center investigation of the effect of HOPE using the XVIVO Heart Preservation System on donor hearts with a projected preservation time of 6-8 hours on 30-day recipient survival and allograft function post-transplant. Each center completed 1 or 2 short preservation time followed by long preservation time cases. PGD was classified as occurring in the first 24 hours after transplantation or secondary (SGD) occurring at any time with a clearly defined cause. Trial survival was compared with a comparator group based on data from the International Society of Heart and Lung Transplantation Registry.<br /><b>Results</b><br />We performed heart transplants using 7 short and 29 long preservation time donor hearts placed on the HOPE system. The mean preservation time for the long preservation time cases was 414 minutes, the longest being 8 hours and 47 minutes. There was 100% survival at 30 days. One long preservation time recipient developed PGD, and 1 developed SGD. One short preservation time patient developed SGD. 30-day survival was superior to the ISHLT comparator group despite substantially longer preservation times in the trial patients.<br /><b>Conclusions</b><br />HOPE provides effective preservation out to preservation times of nearly 9 hours allowing retrieval from remote geographic locations.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Left Atrial Strain in Acute Heart Failure: Clinical and Prognostic Insights.</h4><i>Barki M, Losito M, Caracciolo MM, Sugimoto T, ... Moroni A, Guazzi M</i><br /><b>Aims</b><br />In acute heart failure (AHF), the consequences of impaired left atrial (LA) mechanics are not well understood. We aimed to define the clinical trajectory of LA mechanics by left atrial strain (LAS) analysis.<br /><b>Methods and results</b><br />85 consecutive AHF patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) were enrolled in the LAS-AHF trial and underwent LA mechanics analysis by speckle tracking echocardiography. 77 patients were followed-up at 6 and 12- months. At hospital admission, discharge, 6 and 12-months post-discharge, LA reservoir function (LAS), LA pump strain, LAVi, LA stiffness, indicators of right ventricular (RV) and left ventricular (LV) function, congestion indexes (B lines, IVC, X-ray congestion score index) and biomarkers (NT-pro-BNP) were measured. The primary outcome was time to first event of re-hospitalization, worsening HF or cardiovascular death.From admission to discharge, RV function significantly improved after decongestion, while no significant differences were observed in LA dynamics and LV function. In sinus rhythm patients with mild or no mitral regurgitation, decongestion was associated with a significant improvement of LAS and LA pump strain rate during hospitalization. At 12 months, 24 CV events occurred and of LAS impairment at 12 months follow-up emerged as the most powerful predictor followed by NT-pro-BNP. Kaplan-Meier Curves showed a better survival for LAS >16%, improvement of LAS > 5% and a LAS/LAVi ratio >0.25%/ml/m2 compared to lower cutoff values (log-rank: HR 3.5 CI 95% 1.8-7.3, p = 0.004; log-rank: HR 3.6 CI 95% 2-7.9, p < 0.01; log-rank: HR 3.27 CI 95% 1.4-7.7, p = 0.007).<br /><b>Conclusions</b><br />In AHF of any LVEF, LA dynamics is highly predictive of re-hospitalization and cardiovascular outcome and allows to ease risk-stratification, potentially becoming an early reference target for improving long-term outcome.<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: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Health Status in Heart Failure and Cancer: Analysis of the Medicare Health Outcomes Survey 2016-2020.</h4><i>Shah KP, Khan SS, Baldridge AS, Grady KL, ... Lagu TC, Ahmad FS</i><br /><b>Background</b><br />People with heart failure (HF) and cancer experience impaired physical and mental health status. However, health-related quality of life (HRQOL) has not been directly compared between these conditions in a contemporary population of older people.<br /><b>Objectives</b><br />The authors sought to compare HRQOL in people with HF vs those with lung, colorectal, breast, and prostate cancers.<br /><b>Methods</b><br />The authors performed a pooled analysis of Medicare Health Outcomes Survey data from 2016 to 2020 in participants ≥65 years of age with a self-reported history of HF or active treatment for lung, colon, breast, or prostate cancer. They used the Veterans RAND-12 physical component score (PCS) and mental component score (MCS), which range from 0-100 with a mean score of 50 (based on the U.S. general population) and an SD of 10. The authors used pairwise Student\'s t-tests to evaluate for differences in PCS and MCS between groups.<br /><b>Results</b><br />Among participants with HF (n = 71,025; 54% female, 16% Black), mean PCS was 29.5 and mean MCS 47.9. Mean PCS was lower in people with HF compared with lung (31.2; n = 4,165), colorectal (35.6; n = 4,270), breast (37.7; n = 14,542), and prostate (39.6; n = 17,670) cancer (all P < 0.001). Participants with HF had a significantly lower mean MCS than those with lung (31.2), colon (50.0), breast (52.0), and prostate (53.0) cancer (all P < 0.001).<br /><b>Conclusions</b><br />People with HF experience worse HRQOL than those with cancer actively receiving treatment. The pervasiveness of low HRQOL in HF underscores the need to implement evidence-based interventions that target physical and mental health status and scale multidisciplinary clinics.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 30 Oct 2023; epub ahead of print</small></div>

<div><h4>Applicability and performance of heart failure prognostic scores in dilated cardiomyopathy: The real-world experience of an Italian referral center for cardiomyopathies.</h4><i>Masè M, Rossi M, Setti M, Barbati G, ... Merlo M, Sinagra G</i><br /><b>Background</b><br />The performance of heart failure (HF) risk models is validated in the general population with HF but in specific aetiological settings, and specifically in dilated cardiomyopathy (DCM), has scarcely been explored. We tested eight of the main prognostic scores used in HF in a large real-world population of patients with DCM.<br /><b>Methods</b><br />We included 784 consecutive DCM patients enrolled, both inpatients and outpatients, enrolled between January 2000 and December 2017. The risk of 1 and/or 3-year all-cause mortality/heart transplantation/durable left ventricular assist device (LVAD) implantation (D/HTx/LVAD) was estimated in our cohort according to the following risk scores SHFM, 3-CHF, CHARM, MAGGIC, GISSI-HF, MECKI, Barcelona Bio-HF, Krakow score and their accuracy calculated through the receiver operator characteristic (ROC) curve analysis.<br /><b>Results</b><br />During a median follow-up of 5.8 years (Interquartile Range 3.2-7.6 years), 191 patients (20%) died or underwent HTx/LVAD (158 deaths, 30 heart transplantations, and 3 LVAD implantations). The high missing rate allowed to calculated only four prognostic models (MAGGIC, CHARM, 3-CHF and SHFM). All the scores overestimated the rate of D/HTx/LVAD. The prognostic accuracy was suboptimal for MAGGIC (AUC 0.754) and CHARM (AUC 0.720) scores and only modest for 3-CHF (AUC 0.677) and SHFM (AUC 0.667).<br /><b>Conclusions</b><br />Main prognostic scores for the risk stratification of HF are only partially applicable to real-world patients with DCM. MAGGIC and CHARM scores showed the best accuracy, despite the overestimation of risk. Our findings corroborate the need of specific risk scores for the prognostic stratification of DCM.<br /><b>Clinical perspective</b><br />What is new? The present study is the largest analyses in literature which investigate how the main existing heart failure prognostic risk scores performed in a real-world of dilated cardiomyopathy population, both in- and outpatients. What are the clinical implications? DCM is a stand-alone model of heart failure, where the performance of multiple heart failure prognostic scores for the risk stratification is quite limited. The need for contemporary, dedicated prognostic scores in this disease is increasingly evident.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 29 Oct 2023:131562; 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 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>Ambulatory Seven-Day Mechanical Circulatory Support in Sheep Model of Pulmonary Hypertension and Right Heart Failure.</h4><i>Ukita R, Patel YJ, Kelly Wu W, Francois SA, ... Rosenzweig EB, Bacchetta M</i><br /><b>Objective</b><br />Right heart failure is the major cause of death in pulmonary hypertension. Lung transplantation is the only long-term treatment option for patients who fail medical therapy. Due to the scarcity of donor lungs, there is a critical need to develop durable mechanical support for the failing right heart. A major design goal for durable support is to reduce the size and complexity of devices to facilitate ambulation. Toward this end, we sought to deploy wearable mechanical support technology in a sheep disease model of chronic right heart failure.<br /><b>Methods</b><br />In six sheep with chronic right heart failure, a mechanical support system consisting of an extracorporeal blood pump coupled with a gas exchange unit was attached in a right atrium-to-left atrium configuration for up to seven days. Circuit performance, hematological parameters, and animal hemodynamics were analyzed.<br /><b>Results</b><br />Six subjects underwent the chronic disease model for 56-71 days. Three of the subjects survived to the seven-day endpoint for circulatory support. The circuit provided 2.8 (0.5) L/min of flow compared to the native pulmonary blood flow of 3.5 (1.1) L/min. The animals maintained physiologically balanced blood gas profile with a sweep flow of 1.2 (1.0) L/min. Two animals freely ambulated while wearing the circuit.<br /><b>Conclusions</b><br />Our novel mechanical support system provided physiologic support for a large animal model of pulmonary hypertension with right heart failure. The small footprint of the circuit and the low sweep requirement demonstrate the feasibility of this technology to enable mobile ambulatory applications.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 29 Oct 2023; epub ahead of print</small></div>

<div><h4>Myocardial DNA Damage Predicts Heart Failure Outcome in Various Underlying Diseases.</h4><i>Dai Z, Ko T, Fujita K, Nomura S, ... Saito Y, Komuro I</i><br /><b>Background</b><br />Reliable predictors of treatment efficacy in heart failure have been long awaited. DNA damage has been implicated as a cause of heart failure.<br /><b>Objectives</b><br />The purpose of this study was to investigate the association of DNA damage in myocardial tissue with treatment response and prognosis of heart failure.<br /><b>Methods</b><br />The authors performed immunostaining of DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in endomyocardial biopsy specimens from 175 patients with heart failure with reduced ejection fraction (HFrEF) of various underlying etiologies. They calculated the percentage of nuclei positive for each DNA damage marker (%PAR and %γ-H2A.X). The primary outcome was left ventricular reverse remodeling (LVRR) at 1 year, and the secondary outcome was a composite of cardiovascular death, heart transplantation, and ventricular assist device implantation.<br /><b>Results</b><br />Patients who did not achieve LVRR after the optimization of medical therapies presented with significantly higher %PAR and %γ-H2A.X. The ROC analysis demonstrated good performance of both %PAR and %γ-H2A.X for predicting LVRR (AUCs: 0.867 and 0.855, respectively). There was a negative correlation between the mean proportion of DNA damage marker-positive nuclei and the probability of LVRR across different underlying diseases. In addition, patients with higher %PAR or %γ-H2A.X had more long-term clinical events (PAR HR: 1.63 [95% CI: 1.31-2.01; P < 0.001]; γ-H2A.X HR: 1.48 [95% CI: 1.27-1.72; P < 0.001]).<br /><b>Conclusions</b><br />DNA damage determines the consequences of human heart failure. Assessment of DNA damage is useful to predict treatment efficacy and prognosis of heart failure patients with various underlying etiologies.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 28 Oct 2023; epub ahead of print</small></div>

<div><h4>Efficacy of Dapagliflozin According to Heart Rate: A Patient-Level Pooled Analysis of DAPA-HF and DELIVER.</h4><i>Kondo T, Butt JH, Curtain JP, Jhund PS, ... Solomon SD, McMurray JJV</i><br /><b>Background</b><br />Although elevated resting heart rate (HR) is associated with a higher risk of cardiovascular events in patients with heart failure with reduced ejection fraction in sinus rhythm (SR), the relationship between HR and outcomes among patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction and in those with atrial fibrillation (AF) is uncertain. The aims of this study were to examine the association between baseline HR and outcomes across the range of left ventricular ejection fraction, in patients with and without AF, and evaluate the effect of dapagliflozin according to HR.<br /><b>Methods</b><br />A patient-level pooled analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; heart failure with reduced ejection fraction) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure trial; heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction) trials. The primary outcome of each was the composite of worsening heart failure or cardiovascular death.<br /><b>Results</b><br />Among patients with SR (n=6401, 64%), the rate of the primary outcome was higher in those with higher HR: 16.8 versus 7.7 per 100 person-years for ≥80 bpm versus <60 bpm. The relationship between HR and risk was steeper in heart failure with reduced ejection fraction versus heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction. HR was not associated with outcomes in patients in AF for either heart failure phenotype. The benefit of dapagliflozin on the primary outcome was consistent across the HR range in both SR (<i>P</i><sub>interaction</sub>=0.28) and AF (<i>P</i><sub>interaction</sub>=0.56), for example, for SR <60 bpm, hazard ratio for dapagliflozin versus placebo 0.72 (95% CI, 0.55-0.95); 60 to 69 bpm, 0.78 (0.63-0.97); 70 to 79 bpm, 0.73 (0.59-0.91); ≥80 bpm, 0.77 (0.61-0.97). The benefit was consistent across HR range in both heart failure with reduced ejection fraction and heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction.<br /><b>Conclusions</b><br />The risk of worsening heart failure or cardiovascular death increased with increasing baseline HR among patients in SR, but this association was not seen among patients in AF, irrespective of left ventricular ejection fraction. The benefit of dapagliflozin was consistent across HR range, irrespective of left ventricular ejection fraction or rhythm.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT03036124 and NCT03619213.<br /><br /><br /><br /><small>Circ Heart Fail: 27 Oct 2023:e010898; epub ahead of print</small></div>

<div><h4>Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.</h4><i>Shah RV, Hwang SJ, Murthy VL, Zhao S, ... Lewis GD, Nayor M</i><br /><AbstractText><br /><b>Background:</b><br/>While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify protein signatures of HFpEF exercise responses and new potential therapeutic targets. Methods and Results We analyzed 277 proteins (Olink) in 151 individuals (N=103 HFpEF, 48 controls; 62±11 years; 56% women) with cardiopulmonary exercise testing with invasive monitoring. Using ridge regression adjusted for age/sex, we defined proteomic signatures of 5 physiological variables involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O<sub>2</sub> extraction. Multiprotein signatures of each of the exercise phenotypes captured a significant proportion of variance in respective exercise phenotypes. Interrogating the importance (ridge coefficient magnitude) of specific proteins in each signature highlighted proteins with putative links to HFpEF pathophysiology (eg, inflammatory, profibrotic proteins), and novel proteins linked to distinct physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle, adipose] health) were implicated in impaired O<sub>2</sub> extraction. In a separate sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50-0.90] and 1.43 [95% CI, 1.11-1.85], respectively) with adjustment for clinical factors and B-type natriuretic peptides. <br /><b>Conclusions:</b><br/>The cardiovascular proteome is associated with precision exercise phenotypes in HFpEF, suggesting novel mechanistic targets and potential methods for risk stratification to prevent HFpEF early in its pathogenesis.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 27 Oct 2023:e029980; epub ahead of print</small></div>

<div><h4>Relationship of Race With Functional and Clinical Outcomes With the REHAB-HF Multidomain Physical Rehabilitation Intervention for Older Patients With Acute Heart Failure.</h4><i>Gilbert ON, Mentz RJ, Bertoni AG, Kitzman DW, ... O\'Connor CM, Pastva AM</i><br /><AbstractText><br /><b>Background:</b><br/>The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3-month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health-related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown. Methods and Results In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6-Minute Walk Distance), cognition, depression, frailty, health-related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5-Dimension-5-Level Questionnaire) and at 6 months for hospitalizations and death. Significance level for interactions was <i>P</i>≤0.1. Participants (N=337, 97% of trial population) self-identified in near equal proportions as either Black (48%) or White (52%). The Short Physical Performance Battery intervention effect size was large, with values of 1.3 (95% CI, 0.4-2.1; <i>P</i>=0.003]) and 1.6 (95% CI, 0.8-2.4; <i>P</i><0.001) in Black and White participants, respectively, and without significant interaction by race (<i>P</i>=0.56). Beneficial effects were also demonstrated in 6-Minute Walk Distance, gait speed, and health-related quality of life scores without significant interactions by race. There was an association between intervention and reduced all-cause rehospitalizations in White participants (rate ratio, 0.73 [95% CI, 0.55-0.98]; <i>P</i>=0.034) that appears attenuated in Black participants (rate ratio, 1.06 [95% CI, 0.81-1.41]; <i>P</i>=0.66; interaction <i>P</i>=0.067). <br /><b>Conclusions:</b><br/>The intervention produced similarly large improvements in physical function and health-related quality of life in both older Black and White patients with acute decompensated heart failure. A future study powered to determine how the intervention impacts clinical events is required. REGISTRATION URL: https://www.clinicaltrials.gov. Identifier: NCT02196038.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 27 Oct 2023:e030588; epub ahead of print</small></div>

<div><h4>Acute Heart Failure Is a Malignant Process: But We Can Induce Remission.</h4><i>Cotter G, Davison BA, Lam CSP, Metra M, ... Teerlink JR, Mebazaa A</i><br /><AbstractText>Acute heart failure is a common and increasingly prevalent condition, affecting >10 million people annually. For those patients who survive to discharge, early readmissions and death rates are >30% everywhere on the planet, making it a malignant condition. Beyond these adverse outcomes, it represents one of the largest drivers of health care costs globally. Studies in the past 2 years have demonstrated that we can induce remissions in this malignant process if therapy is instituted rapidly, at the first acute heart failure episode, using full doses of all available effective medications. Multiple studies have demonstrated that this goal can be achieved safely and effectively. Now the urgent call is for all stakeholders, patients, physicians, payers, politicians, and the public at large to come together to address the gaps in implementation and enable health care providers to induce durable remissions in patients with acute heart failure.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 27 Oct 2023:e031745; epub ahead of print</small></div>

<div><h4>Prognostic Value of Natriuretic Peptide Levels for Adverse Renal Outcomes in Patients With Moderate to Severe Acute Kidney Injury With or Without Heart Failure.</h4><i>Chaikijurajai T, Demirjian S, Tang WHW</i><br /><AbstractText><br /><b>Background:</b><br/>Natriuretic peptides have been recommended as biomarkers for the diagnosis and prognosis of patients with heart failure and are often elevated in the setting of acute kidney injury. We sought to demonstrate the associations between increased baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) and adverse renal outcomes in patients with moderate-to-severe acute kidney injury. Methods and Results We reviewed electronic medical records of consecutive patients with acute kidney injury stage 2 and 3 admitted to the Cleveland Clinic between September 2011 and December 2021. Patients with NT-proBNP levels collected before renal consultation or dialysis initiation were included. Adverse renal outcomes included dialysis requirement and dialysis dependence defined as patients undergoing dialysis within 72 hours before hospital discharge or in-hospital mortality. In our study cohort (n=3811), 2521 (66%) patients underwent dialysis, 1619 (42%) patients became dialysis dependent, and 1325 (35%) patients had in-hospital mortality. After adjusting for cardiorenal risk factors, compared with the lowest quartile, the highest quartile of NT-proBNP (≥18 215 pg/mL) was associated with increased likelihood of dialysis requirement (adjusted odds ratio [OR], 2.36 [95% CI, 1.87-2.99]), dialysis dependence (adjusted OR, 1.89 [95% CI, 2.53-1.34]), and in-hospital mortality (adjusted OR, 1.34 [95% CI, 1.01-1.34]). <br /><b>Conclusions:</b><br/>Increased NT-proBNP was associated with an increased risk of dialysis requirement, becoming dialysis dependent, and in-hospital mortality in patients with moderate-to-severe acute kidney injury.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 27 Oct 2023:e031453; epub ahead of print</small></div>

<div><h4>What about chronotropic incompetence in heart failure with mildly reduced ejection fraction? Clinical and prognostic implications from the MECKI score data-set.</h4><i>Magrì D, Gallo G, Piepoli M, Salvioni E, ... Di Lenarda A, Agostoni P</i><br /><b>Aims</b><br />Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction (HFrEF), however no data on its clinical and prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF). Therefore, the study aims to investigate, in a large multicenter HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters.<br /><b>Methods</b><br />Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analyzed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored.<br /><b>Results</b><br />CI prevalence differed depending on the method (peak heart rate, pHR% versus pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR%≤65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 year. At multivariate analysis, both pHR% [Hazard Ratio 0.97(0.95-0.99), p < 0.05] and pHRR% [Hazard Ratio 0.977(0.961-0.993), p < 0.01) were associated with the primary end-point. A pHR%≤75% and a pHRR%≤50% represented the most accurate cut-off values in predicting the outcome.<br /><b>Conclusions</b><br />The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.<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: 27 Oct 2023; epub ahead of print</small></div>

<div><h4>Hypotension in heart failure is less harmful if associated with high or increasing doses of heart failure medication: Insights from the Swedish Heart Failure Registry.</h4><i>Girerd N, Coiro S, Benson L, Savarese G, ... Rossignol P, Lund LH</i><br /><b>Background</b><br />Heart failure (HF) medication may reduce blood pressure (BP). Low BP is associated with worse outcomes but how this association is modified by HF medication has not been studied. We evaluated the association between BP and outcomes according to HF medication dose in HF with reduced ejection fraction (HFrEF).<br /><b>Methods</b><br />We studied HFrEF patients from the Swedish HF registry (2000-2018). Associations between systolic BP (SBP) and cardiovascular death and/or HF hospitalization (CVD/HFH) were analyzed according to doses of renin-angiotensin system (RAS) inhibitors, beta-blockers and mineralocorticoid receptor antagonists (MRA).<br /><b>Results</b><br />Among 42 040 patients (median age 74.0), lower baseline SBP was associated with higher risk of CVD/HFH (adjusted HR per 10 mmHg higher SBP: 0.92 [0.92-0.93]), which was less high risk under optimized RAS inhibitors and beta-blockers doses (10% decrease in event rates per 10 mmHg SBP increase in untreated patients versus 7% decrease in patients at maximum dose, both adjusted p < 0.02). Among the 13 761 patients with repeated measurements, 9.9% reported a SBP decrease >10 mmHg when HF medications\' doses were increased, whereas 24.6% reported a SBP decrease >10 mmHg with stable/decreasing doses. Decreasing SBP was associated with higher risk of CVD/HFH in patients with stable (HR = 1.10 [1.04-1.17]) or decreasing (HR = 1.29 [1.18-1.42]) HF medication dose but not in patients with an increase in doses (HR = 0.94 [0.86-1.02]).<br /><b>Conclusions</b><br />The association of lower SBP with higher risk of CVD/HFH is attenuated in patients with optimized HF medication. These results suggest that low or declining SBP should not limit HF medication optimization. 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: 26 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>Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation.</h4><i>Kouranos V, Khattar RS, Okafor J, Ahmed R, ... Lüscher TF, Sharma R</i><br /><b>Aims</b><br />Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients.<br /><b>Methods and results</b><br />Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, ECG, echocardiography, cardiac magnetic resonance imaging (CMR) and <sup>18</sup> -Flourodeoxyglucose positron emission tomography (FDG- PET) at baseline. The composite endpoint consisted of all-cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4±12 years of age). During median follow-up of 2.2 years (range:1 month-11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5-year and 10-year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (HR:2.41, 95%CI 1.34-4.31, p=0.003), CMR-LVEF (HR:0.96, 95%CI 0.94-0.98, p<0.0001) and maximum Standardized Uptake Value (SUVmax) of FDG-PET; HR:1.11; 95%CI 1.04-1.19, p=0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups.<br /><b>Conclusion</b><br />CS is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes. 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: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Qiliqiangxin: a Multifaceted Holistic Treatment for Heart Failure or a Pharmacological Probe for the Identification of Cardioprotective Mechanisms?</h4><i>Packer M</i><br /><AbstractText>The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signaling through nutrient surplus and nutrient deprivation pathways. Qiliqiangxin (QLQX) is a commercial formulation of 11 different plant ingredients, whose active compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 and Re) and periplocymarin. In the QUEST Trial, QLQX reduced the combined risk of cardiovascular death or heart failure hospitalization (hazard ratio 0.78 [95% CI 0.68-0.90]), based on 859 events in 3119 patients over a median of 18.2 months; the benefits were seen in patients taking foundational drugs except for SGLT2 inhibitors. Numerous experimental studies of QLQX in diverse cardiac injuries have yielded highly consistent findings. In marked abrupt cardiac injury, QLQX mitigated cardiac injury by upregulating nutrient surplus signaling through the PI3K/Akt/mTOR/HIF-1α/NRF2 pathway; the benefits of QLQX were abrogated by suppression of PI3K, Akt, mTOR, HIF-1α or NRF2. In contrast, in prolonged measured cardiac stress (as in chronic heart failure), QLQX ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, and proinflammatory and profibrotic pathways, while enhancing mitochondrial health and promoting glucose and fatty acid oxidation and ATP production. These effects are achieved by an action of QLQX to upregulate nutrient deprivation signaling through SIRT1/AMPK/PGC-1α and enhanced autophagic flux. In particular, QLQX appears to enhance the interaction of PGC-1α with PPARα, possibly by direct binding to RXRα; silencing of SIRT1, PGC-1α and RXRα abrogated the favorable effects of QLQX in the heart. Since PGC-1α/RXRα is also a downstream effector of Akt/mTOR signaling, the actions of QLQX on PGC-1α/RXRα may explain its favorable effects in both acute and chronic stress. Intriguingly, the individual ingredients in QLQX - astragaloside IV, ginsenosides, and tanshione IIA - share QLQX\'s effects on PGC-1α/RXRα/PPARα signaling. QXQL also contains periplocymarin, a cardiac glycoside that inhibits Na+-K+-ATPase. Taken collectively, these observations support a conceptual framework for understanding the mechanism of action for QLQX in heart failure. The high likelihood of overlap in the mechanism of action of QLQX and SGLT2 inhibitors requires additional experimental studies and clinical trials. This article is protected by copyright. All rights reserved.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Right ventricular free wall and four-chamber longitudinal strain in relation to incident heart failure in the general population.</h4><i>Espersen C, Skaarup KG, Lassen MCH, Johansen ND, ... Møgelvang R, Biering-Sørensen T</i><br /><b>Background</b><br />Right ventricular free wall (RVFWLS) and four-chamber longitudinal strain (RV4CLS) are associated with adverse events in various patient populations including patients with heart failure (HF). We sought to investigate the prognostic value of RVFWLS and RV4CLS for the development of incident HF in participants from the general population.<br /><b>Methods</b><br />Participants from the 5th Copenhagen City Heart Study (2011-2015) without known chronic ischemic heart disease or HF at baseline were included. RVFWLS and RV4CLS were obtained using two-dimensional speckle-tracking echocardiography from the RV-focused apical four-chamber view. The primary endpoint was incident HF.<br /><b>Results</b><br />Among 2,740 participants (mean age 54 ± 17 years, 42% male), 43 (1.6%) developed HF during a median follow-up of 5.5 years (IQR 4.5-6.3). Both RVFWLS and RV4CLS were associated with an increased risk of incident HF during follow-up independent of age, sex, hypertension, diabetes, body mass index and tricuspid annular plane systolic excursion (TAPSE), (HR 1.06, 95%CI 1.00-1.11, p = 0.034, per 1% absolute decrease and HR 1.14, 95%CI 1.05-1.23, p = 0.001, per 1% absolute decrease, respectively). Left ventricular ejection fraction (LVEF) modified the association between RV4CLS and incident HF (p for interaction = 0.016) such that RV4CLS was only of prognostic importance among those with LVEF < 55% (HR 1.21, 95%CI 1.11-1.33, p < 0.001 vs. HR 0.94, 95%CI 0.80-1.10, p = 0.43 in patients with LVEF ≥ 55%).<br /><b>Conclusions</b><br />In participants from the general population, both RVFWLS and RV4CLS were associated with an increased risk of incident HF independent of important baseline characteristics and TAPSE, and LVEF modified the relationship between RV4CLS and incident 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 Heart J Cardiovasc Imaging: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Clustering properties of the cardiac ryanodine receptor in health and heart failure.</h4><i>Waddell HMM, Mereacre V, Alvarado FJ, Munro ML</i><br /><AbstractText>The cardiac ryanodine receptor (RyR2) is an intracellular Ca<sup>2+</sup> release channel vital for the function of the heart. Physiologically, RyR2 is triggered to release Ca<sup>2+</sup> from the sarcoplasmic reticulum (SR) which enables cardiac contraction; however, spontaneous Ca<sup>2+</sup> leak from RyR2 has been implicated in the pathophysiology of heart failure (HF). RyR2 channels have been well documented to assemble into clusters within the SR membrane, with the organisation of RyR2 clusters recently gaining interest as a mechanism by which the occurrence of pathological Ca<sup>2+</sup> leak is regulated, including in HF. In this review, we explain the terminology relating to key nanoscale RyR2 clustering properties as both single clusters and functionally grouped Ca<sup>2+</sup> release units, with a focus on the advancements in super-resolution imaging approaches which have enabled the detailed study of cluster organisation. Further, we discuss proposed mechanisms for modulating RyR2 channel organisation and the debate regarding the potential impact of cluster organisation on Ca<sup>2+</sup> leak activity. Finally, recent experimental evidence investigating the nanoscale remodelling and functional alterations of RyR2 clusters in HF is discussed with consideration of the clinical implications.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Ltd.<br /><br /><small>J Mol Cell Cardiol: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>The Impact of the COVID-19 Pandemic on Drug Overdoses in the United States and the Effect on Cardiac Transplant Volume and Survival.</h4><i>Phillips KG, James L, Rabadi M, Grossi EA, ... Galloway AC, Moazami N</i><br /><b>Objectives</b><br />Drug overdose (DO) deaths rose to unprecedented levels during the COVID-19 pandemic. This study examines the impact of COVID-19 on the availability of cardiac allografts from DO donors and the implications of DO donor use on recipient survival.<br /><b>Methods</b><br />Heart transplants reported to the United Network for Organ Sharing (UNOS) from January 2017-November 2019 (\"pre-COVID\") and March 2020-June 2021 (\"COVID pandemic\") were analyzed with respect to DO donor status. Outcomes were analyzed using Kaplan-Meier survival and Cox-regression to identify predictors of survival. Characteristics of discarded cardiac allografts were also compared by DO donor status.<br /><b>Results</b><br />During the COVID-19 pandemic 27.2% of cardiac allografts were from DO donors versus 20.5% pre-COVID, a 32.7% increase (p<0.001). During the pandemic, DO donors were younger (84.7% vs. 76.3% <40 years, p<0.001), had higher cigarette use (16.1% vs. 10.8%, p<0.001), higher cocaine use (47.4% vs. 19.7%, p<0.001), and higher incidence of hepatitis C antibodies (26.8% vs. 6.1%, p<0.001) and RNA positivity (16.2% vs. 4.2%, p<0.001). While DO donors were less likely to require inotropic support (30.8% vs. 35.4%, p=0.008), they were more likely to have received cardiopulmonary resuscitation (CPR) (95.3% vs. 43.2%,p<0.001). Recipient survival was equivalent using Kaplan-Meier analysis (log-rank, p=0.33) and survival probability at 36 months was 85.6% (n. at risk=398) for DO donors versus 83.5% (n. at risk=1633) for all other donors. Cox-regression demonstrated that DO donor status did not predict mortality (HR 1.05; 95% CI 0.90-1.23, p=0.53).<br /><b>Conclusions</b><br />During the COVID-19 pandemic there was a 32.7% increase in heart transplants utilizing DO donor hearts, and DO became the most common mechanism of death for donors. The use of DO donor hearts did not have an impact on short-term recipient survival.<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 Oct 2023; epub ahead of print</small></div>

<div><h4>Clinical Utility of Patient-Reported Outcome Instruments in the Management of Pulmonary Hypertension: A Systematic Review.</h4><i>Rose SW, Highland KB, Kelkar AA</i><br /><b>Background</b><br />Despite the greater sensitivity and specificity of disease-specific patient-reported outcome measures (PROM) to detect clinical change, only recently have such instruments been developed for pulmonary hypertension (PH), specifically pulmonary arterial hypertension (PAH) and chronic thromboembolic disease (CTEPH). Although these valuable tools are now being incorporated into clinical studies of PH, they have not yet reached widespread integration into routine clinical care.<br /><b>Objectives</b><br />In this systematic review, we assess the psychometric properties of PROM developed for PH, compare PROM with other clinical outcomes in PH, and address the utility of PROM in clinical care.<br /><b>Methods</b><br />The authors performed a systematic search of papers published between January 1, 2006, and October 1, 2022, using the MEDLINE database to identify PROM developed and validated for PH. The identified PROM were found to have been developed only in groups with PAH and CTEPH. The authors evaluated the identified instruments according to established psychometric criteria. An additional search was performed to identify randomized controlled trials (RCTs)∖utilizing these PROM for comparison with clinical outcomes.<br /><b>Results</b><br />From 527 papers retrieved, a total of 35 PROM were identified. Of these, 5 disease-specific instruments were included in the final analysis. While both Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and XXX (emPHasis-10) performed well in patients with PAH and CTEPH with regard to their psychometric properties, emPHasis-10 demonstrated superior feasibility for use in clinical practice due to its concise format. The Pulmonary Arterial Hypertension-Symptoms and Impacts Questionnaire performed well in the authors\' analysis, though additional data is needed regarding interpretability and feasibility.<br /><b>Conclusions</b><br />EmPHasis-10 demonstrated strong psychometric properties and the greatest feasibility for clinical use. Further study assessing the integration of PROM into routine clinical care for PH is needed.<br /><br />Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Impaired T cell IRE1α-XBP1 signaling directs inflammation in experimental Heart Failure with Preserved Ejection Fraction.</h4><i>Smolgovsky S, Bayer AL, Kaur K, Sanders E, ... Cubillos-Ruiz JR, Alcaide P</i><br /><AbstractText>Heart Failure with Preserved Ejection Fraction (HFpEF) is a widespread syndrome with limited therapeutic options and poorly understood immune-pathophysiology. Using a two-hit preclinical model of cardiometabolic HFpEF that induces obesity and hypertension, we found that cardiac T cell infiltration and lymphoid expansion occur concomitantly with cardiac pathology, and that diastolic dysfunction, cardiomyocyte hypertrophy and cardiac phospholamban phosphorylation are T cell-dependent. Heart-infiltrating T cells were not restricted to cardiac antigens and were uniquely characterized by impaired activation of the Inositol-requiring enzyme-1α (IRE1α)-X-box binding protein 1 (XBP1) arm of the unfolded protein response. Notably, selective ablation of XBP1 in T cells enhanced their persistence in the heart and lymphoid organs of mice with preclinical HFpEF. Furthermore, T cell IRE1α-XBP1 activation was restored after withdrawal of the two comorbidities inducing HFpEF, resulting in partial improvement of cardiac pathology. Our results demonstrate that diastolic dysfunction and cardiomyocyte hypertrophy in preclinical HFpEF are T cell-dependent, and that reversible dysregulation of the T cell IRE1α-XBP1 axis is a T cell signature of HFpEF.</AbstractText><br /><br /><br /><br /><small>J Clin Invest: 24 Oct 2023; epub ahead of print</small></div>

<div><h4>Reverse Remodeling Effects of Sacubitril-Valsartan: Structural and Functional Optimization in Stage C Heart Failure.</h4><i>Kalanatari S, Oren D, Medvedofsky D, Narang A, ... Lang RM, Uriel N</i><br /><b>Background</b><br />Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, reduces all-cause mortality as well as the rate of heart failure hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the benefits of initiating sacubitril-valsartan on ventricular remodeling in patients previously optimized on guideline directed medical therapy.<br /><b>Methods</b><br />In this prospective, single-arm longitudinal study, 40 patients with HFrEF who were optimized on guideline-directed medical therapy were transitioned to sacubitril-valsartan. The primary end-point was the change in left ventricular (LV) volume at 1 year as assessed by three dimensional transthoracic echocardiography. Other echocardiographic endpoints included change in LV function and change in right ventricular (RV) size and function.<br /><b>Results</b><br />The mean age was 55 ± 12 years and 63% were male. At 1 year, LV end-diastolic volume decreased from 242 ± 71 to 157 ± 57 ml (p <0.001) with a corresponding increase in LV ejection fraction from 32 ± 7 to 44 ± 9 % (p <0.001). RV end-diastolic volume decreased from 151 ± 51 to 105 ± 45 ml (p <0.001). While RV ejection fraction did not change (51 ± 8 vs 51 ± 10; p = 0.35), RV GLS improved from -14.9 ± 3.4 % to -19.3 ± 4.3 % (p <0.001) <br /><b>Conclusion:</b><br/>When added to standard medical therapy for heart failure, sacubitril-valsartan induces significant remodeling of both the right and left ventricles as assessed by 3D echocardiography.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am J Cardiol: 24 Oct 2023; epub ahead of print</small></div>

<div><h4>Echocardiographic Reference Ranges of Global Longitudinal Strain for All Cardiac Chambers Using Guideline-Directed Dedicated Views.</h4><i>Nyberg J, Jakobsen EO, Østvik A, Holte E, ... Grenne B, Dalen H</i><br /><b>Background</b><br />Myocardial deformation by echocardiographic strain imaging is a key measurement in cardiology, providing valuable diagnostic and prognostic information. Reference ranges for strain should be established from large healthy populations with minimal methodologic biases and variability.<br /><b>Objectives</b><br />The aim of this study was to establish echocardiographic reference ranges, including lower normal limits of global strains for all 4 cardiac chambers, by guideline-directed dedicated views from a large healthy population and to evaluate the influence of subject-specific characteristics on strain.<br /><b>Methods</b><br />In total, 1,329 healthy participants from HUNT4Echo, the echocardiographic substudy of the fourth wave of the Trøndelag Health Study, were included. Echocardiographic recordings specific for each chamber were optimized according to current recommendations. Two experienced sonographers recorded all echocardiograms using GE HealthCare Vivid E95 scanners. Analyses were performed by experts using GE HealthCare EchoPAC.<br /><b>Results</b><br />The reference ranges for left ventricular (LV) global longitudinal strain and right ventricular free-wall strain were -24% to -16% and -35% to -17%, respectively. Correspondingly, left atrial (LA) and right atrial (RA) reservoir strains were 17% to 49% and 17% to 59%. All strains showed lower absolute values with higher age, except for LA and RA contractile strains, which were higher. The feasibility for strain was overall good (LV 96%, right ventricular 83%, LA 94%, and RA 87%). All chamber-specific strains were associated with age, and LV strain was associated with sex.<br /><b>Conclusions</b><br />Reference ranges of strain for all cardiac chambers were established based on guideline-directed chamber-specific recordings. Age and sex were the most important factors influencing reference ranges and should be considered when using strain echocardiography.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Imaging: 24 Oct 2023; epub ahead of print</small></div>

<div><h4>Palliative Care for Patients With Heart Failure With Preserved Ejection Fraction.</h4><i>Godfrey S, Peng Y, Lorusso N, Sulistio M, ... Pandey A, Warraich H</i><br /><AbstractText>Heart failure with preserved ejection fraction (HFpEF) has become the leading form of heart failure worldwide, particularly among elderly patient populations. HFpEF is associated with significant morbidity and mortality that may benefit from incorporation of palliative care (PC). Patients with HFpEF have similarly high mortality rates to patients with heart failure with reduced ejection fraction. PC trials for heart failure have shown improvement in quality of life, quality of death, and health care utilization, although most trials defined heart failure clinically without differentiating between HFpEF and heart failure with reduced ejection fraction. As such, the timing and role of PC for HFpEF care remains uncertain, and PC referral rates for HFpEF are very low despite potential improvements in important patient-centered outcomes. Specific barriers to referral include limited data, prognostic uncertainty, provider misconceptions about PC, inadequate specialty PC workforce, complexities of treating multimorbidity, and limited home care options for patients with heart failure. While there are many barriers to integration of PC into HFpEF care, there are multiple potential benefits to patients with HFpEF throughout their disease course. As this population continues to grow, targeted efforts to study and implement PC interventions are needed to improve patient quality of life and death.</AbstractText><br /><br /><br /><br /><small>Circ Heart Fail: 23 Oct 2023:e010802; epub ahead of print</small></div>

<div><h4>Effect of Dapagliflozin on 6-Minute Walk Distance in Heart Failure With Preserved Ejection Fraction: PRESERVED-HF.</h4><i>Lewis GD, Gosch K, Cohen LP, Nassif ME, ... Kosiborod MN, Sauer AJ</i><br /><b>Background</b><br />Heart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin.<br /><b>Methods</b><br />We performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure).<br /><b>Results</b><br />A total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; <i>P</i>=0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; <i>P</i>=0.03). These results were consistent across all prespecified subgroups (all <i>P</i> values for interaction were not significant).<br /><b>Conclusions</b><br />Compared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: PRESERVED-HF NCT03030235.<br /><br /><br /><br /><small>Circ Heart Fail: 23 Oct 2023:e010633; epub ahead of print</small></div>

<div><h4>Comprehensive Vasodilation in Women with Acute Heart Failure: Novel Insights from the GALACTIC randomized controlled trial.</h4><i>Wussler D, Belkin M, Maeder MT, Walter J, ... Mueller C, GALACTIC Investigators</i><br /><b>Background:</b><br/>and aims</b><br />Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately.<br /><b>Methods and results</b><br />We performed a predefined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilation versus usual care in an international, multicenter, open-label, blinded-end-point trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥ 100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 versus 76 years), had a lower body weight (median 64.5 versus 77.6 kg) and lower estimated glomerular filtration rate (median 48 versus 54 mL/min per 1,73 m<sup>2</sup> ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62 [95% CI, 1.05-2.50]; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men, respectively).<br /><b>Conclusion</b><br />Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF. 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 Oct 2023; epub ahead of print</small></div>

<div><h4>Evaluation of Madit II Risk Stratification Score among Nationwide Registry of Heart Failure Patients with Primary Prevention Implantable Cardiac Defibrillators or Resynchronization Therapy Devices.</h4><i>Rav-Acha M, Wube O, Brodie OT, Michowitz Y, ... Goldenberg I, Glikson M</i><br /><AbstractText>Current guidelines advocate prophylactic Implantable Cardioverter Defibrillator (ICD) for all symptomatic heart failure (HF) patients with low LVEF. Since many patients will never use their device, a score delineating subgroups with differential ICD benefit is crucial. We aimed to Evaluate MADIT II-based Risk Stratification Score (MRSS) feasibility to delineate ICD survival benefit among nationwide registry of HF patients with prophylactic ICDs. Accordingly, all Israeli HF patients with prophylactic ICD/CRTDs were categorized into MRSS-based risk-subgroups. Study endpoints included overall mortality, sustained ventricular arrhythmia (VA), and a competing risk of VA (potential preventable arrhythmic death, where ICD could benefit survival) versus non-arrhythmic death. Potential ICD survival benefit was estimated by the area between these cumulative incidence curves. Among 2,177 HF patients implanted prophylactic device, 189 patients (8.7%) had VA and 316 (14.5%) died during median Follow-up (F/U) of 2.9 years. MRSS risk-subgroups were significantly associated with overall mortality (p < 0.001) and weakly with VA (p 0.3). Competing risk analysis of VA versus non-arrhythmic death revealed significantly shorter duration (p < 0.001) and smaller magnitude of ICD survival benefit with increased risk subgroups, yielding estimated 76, 60, 38, and 0 life-days gained from prophylactic ICD implant during 5-year F/U for the MRSS low, intermediate, high, and very-high risk subgroups, respectively (p for trend< 0.05). In conclusion, MRSS use among nationwide registry of ischemic and non-ischemic cardiomyopathy patients, revealed subgroups with differing ICD survival benefit, suggesting it could help evaluate prophylactic ICD survival benefit.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am J Cardiol: 23 Oct 2023; epub ahead of print</small></div>

<div><h4>Clinical implication of NT-proBNP burden in heart failure with reduced ejection fraction: from the GUIDE-IT.</h4><i>Dong B, Chen C, Zheng Y, Dong Y, ... Xue R, Cong C</i><br /><b>Aims</b><br />The aim of the study was to explore the prognostic implication of N-terminal pro-brain natriuretic peptide (NT-proBNP) burden on heart failure with reduced ejection fraction (HFrEF).<br /><b>Methods</b><br />We performed a post-hoc analysis of the GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) trial. NT-proBNP burden was defined as the proportion of days with elevated NT-proBNP (≥1800 pg/ml) to the whole observation time. Cox proportional hazards regression model was used to evaluate the association with NT-proBNP burden and prognosis.<br /><b>Results</b><br />A total of 815 patients with HFrEF were analyzed in our study. Patients were categorized into 4 groups according to the degree of NT-proBNP burden. In the multivariate cox analysis, NT-proBNP burden was significantly associated with all-cause mortality, cardiovascular (CV) mortality and HF hospitalization. Compared to patients without NT-proBNP burden, the risk for composite outcome increased by 210% (HR 3.10, 95% CI 1.72-5.58, p<0.001) in NT-proBNP burden 1 (mild) group, 432% (HR 5.32, 95% CI 2.93-9.67, p<0.001) in NT-proBNP burden 2 (moderate) group and over 12 times (HR 13.15, 95% CI 7.42-23.33, p<0.001) in NT-proBNP burden 3 (severe) group. Sensitivity analyses stratified by age and renal function yielded similar results.<br /><b>Conclusions</b><br />Higher NT-proBNP burden was associated with significant increase in risks of all-cause mortality, CV mortality, HF hospitalization and composite outcome. The results suggested that NT-proBNP burden could be an important predictor of the prognosis of patients with HFrEF.<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 22 Oct 2023; epub ahead of print</small></div>