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Heart failure (HF) poses a major global health challenge with rising prevalence, significant morbidity and mortality, and substantial associated healthcare costs. With aging of the population and an increasing burden of comorbidities, the complex interplay between cardiovascular, kidney, and metabolic risk factors have been thrust into the spotlight and have broadened the traditional focus from HF treatment to an increased emphasis on prevention. In recognition of the evolving HF landscape, the American Heart Association released the PREVENT models which are comprehensive risk assessment tools that estimate 10- and 30-year risk of incident cardiovascular disease and its subtypes, including atherosclerotic cardiovascular disease (ASCVD) and, for the first time, HF. While it is an accurate risk estimation tool and represents a step forward in improving risk stratification for primary prevention of HF, there remain several limitations and unknowns like model performance across disaggregated racial and ethnic groups, the role of traditional ASCVD vs. HF-specific risk factors, HF prediction among those with known ASCVD, and the use of traditional regression techniques in lieu of potentially more powerful machine learning-based modeling approaches. Furthermore, it remains unclear how to optimize risk estimation in clinical care. The emergence of multiple novel pharmacological therapies that prevent incident HF, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists (MRAs), highlights the importance of accurate HF risk prediction. To provide HF prevention with these effective but costly therapies, we must understand the optimal strategy in sequencing and combining these therapies and prioritize patients at highest risk. Such implementation requires both accurate risk stratification and a better understanding of how to communicate risk to patients and providers. This state-of-the-art review aims to provide a comprehensive overview of recent trends in HF prevention, including risk assessment, care management strategies, and emerging and novel treatments. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease worldwide and may present with or without dynamic left ventricular outflow tract obstruction (LVOTO). Significant advances have been made in the management of obstructive HCM. On the other hand, despite their significant symptomatic burden, patients with non-obstructive HCM (nHCM) (i.e., without LVOTO) still do not have evidence-based therapeutical options. The recent IMPROVE-HCM study, a phase 2 randomized, double-blinded trial, aims to place a first step in filling this gap in knowledge. The study assessed the safety (primary endpoint) and efficacy (secondary endpoint) of ninerafaxstat, a novel cardiac mitotrope drug that increases adenosine triphosphate production. We highlighted the main findings of the trial, contextualizing these results within the larger landscape of completed and ongoing trials in nHCM. [ABSTRACT FROM AUTHOR]

Introduction: Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes. Methods: This retrospective cohort study included Reasons for Geographic and Racial Differences in Stroke (REGARDS) participants aged at least 65 years hospitalized for heart failure between 2003 and 2014. We calculated changes between hospital admission and discharge in medication count (Δcount) and in the validated Medication Regimen Complexity Index (ΔMRCI), which incorporates each medication's dosage formulation, frequency, timing, and special instructions. The primary outcome was a composite of 90-day all-cause readmission and all-cause mortality post-discharge. We calculated ΔMRCI and Δcount, identified their predictors, and examined their association with the primary outcome. Results: Among 725 patients hospitalized for heart failure, the mean (SD) age was 77 (7.2) years, 46% were female, and 35% were Black. At discharge, nearly 75% had an increase in their medication regimen complexity and 60% had an increase in their medication count. Patients with the highest ΔMRCI and Δcount were more likely to be female and Black. Predictors of the highest ΔMRCI included Charlson comorbidity index and not being discharged home; predictors of the highest Δcount included intensive care unit stay. Approximately 48% of patients experienced a 90-day readmission or death. Neither ΔMRCI (highest versus lowest tertile; HR 1.14, 95% CI 0.86, 1.50) nor Δcount (HR 0.97, 95% CI 0.73, 1.27) were associated with 90-day outcomes. Conclusion: Following a heart failure hospitalization, increased medication regimen complexity was common but was not associated with 90-day post-hospitalization outcomes. These are reassuring data, suggesting that it is reasonable for clinicians to focus on optimizing medication regimens for patients with heart failure even if it increases regimen complexity. [ABSTRACT FROM AUTHOR]

Natural language processing (NLP) is a burgeoning field of machine learning/artificial intelligence that focuses on the computational processing of human language. Researchers and clinicians are using NLP methods to advance the field of medicine in general and in heart failure (HF), in particular, by processing vast amounts of previously untapped semi-structured and unstructured textual data in electronic health records. NLP has several applications to clinical research, including dramatically improving processes for cohort assembly, disease phenotyping, and outcome ascertainment, among others. NLP also has the potential to improve direct clinical care through early detection, accurate diagnosis, and evidence-based management of patients with HF. In this state-of-the-art review, we present a general overview of NLP methods and review clinical and research applications in the field of HF. We also propose several potential future directions of this emerging and rapidly evolving technological breakthrough. [ABSTRACT FROM AUTHOR]

Aims: Worsening heart failure (WHF) events occurring in non‐inpatient settings are becoming increasingly recognized, with implications for prognostication. We evaluate the performance of a natural language processing (NLP)‐based approach compared with traditional diagnostic coding for non‐inpatient clinical encounters and left ventricular ejection fraction (LVEF). Methods and results: We compared characteristics for encounters that did vs. did not meet WHF criteria, stratified by care setting [i.e. emergency department (ED) and observation stay]. Overall, 8407 (22%) encounters met NLP‐based criteria for WHF (3909 ED visits and 4498 observation stays). The use of an NLP‐derived definition adjudicated 3983 (12%) of non‐primary HF diagnoses as meeting consensus definitions for WHF. The most common diagnosis indicated in these encounters was dyspnoea. Results were primarily driven by observation stays, in which 2205 (23%) encounters with a secondary HF diagnosis met the WHF definition by NLP. Conclusions: The use of standard claims‐based adjudication for primary diagnosis in the non‐inpatient setting may lead to misclassification of WHF events in the ED and overestimate observation stays. Primary diagnoses alone may underestimate the burden of WHF in non‐hospitalized settings. [ABSTRACT FROM AUTHOR]

The article discusses the ARISE-HF trial, which aimed to evaluate the safety and efficacy of a novel aldose reductase inhibitor (AT-001) in patients with diabetic cardiomyopathy (DbCM) and stage B heart failure (HF). DbCM is a complication of type 2 diabetes mellitus (T2DM) that can lead to structural and functional abnormalities in the heart. The study found that AT-001 did not significantly improve exercise capacity compared to placebo, but there was a potential benefit in patients not receiving other cardioprotective drugs. However, further research is needed to confirm these findings and determine the clinical role of AT-001 in combination with other therapies. [Extracted from the article]

Aims: Biologically active adrenomedullin (bio‐ADM) is a promising marker of residual congestion. The STRONG‐HF trial showed that high‐intensity care (HIC) of guideline‐directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio‐ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated. Methods and results: We measured plasma bio‐ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio‐ADM correlated with most signs of congestion, with the exception of rales. Changes in bio‐ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma −0.24; p = 0.0001). Patients in the highest tertile of baseline bio‐ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180‐day all‐cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42–3.22) and 180‐day HF rehospitalization (HR 2.33, 95% CI 1.38–3.94). Areas under the receiver‐operating characteristic curves were 0.5977 (95% CI 0.5561–0.6393), 0.5800 (95% CI 0.5356–0.6243), and 0.6159 (95% CI 0.5711–0.6607) for bio‐ADM, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and their combination, respectively, suggesting that both bio‐ADM and NT‐proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio‐ADM and NT‐proBNP than NT‐proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio‐ADM concentration (interaction p = 0.37). In contrast to NT‐proBNP, the 90‐day change in bio‐ADM did not differ significantly between HIC and usual care. Conclusions: Bio‐ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio‐ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT‐proBNP. [ABSTRACT FROM AUTHOR]

Aim: The TRANSFORM‐HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non‐adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on‐treatment analysis inclusive of all randomized patients except those confirmed non‐adherent to study diuretic. Methods and results: TRANSFORM‐HF was an open‐label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator‐selected dosage. This post‐hoc on‐treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non‐adherent to study diuretic. This modified on‐treatment definition was applied separately at time of hospital discharge and 30‐day follow‐up. All‐cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on‐treatment analyses at discharge and 30‐day follow‐up, respectively. There was no significant difference in all‐cause mortality between torsemide and furosemide in patients on‐treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83–1.22], p = 0.96) and at 30‐day follow‐up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81–1.27], p = 0.90). All‐cause mortality or all‐cause hospitalization was similar between torsemide and furosemide in patients who were on‐treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82–1.03]) and 30‐day follow‐up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82–1.05]). In patients who were on‐treatment at 30‐day follow‐up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86–1.14], p = 0.87). Conclusions: In TRANSFORM‐HF, a post‐hoc on‐treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide. Clinical Trail Registration: ClinicalTrials.gov Identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. Methods: PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. Results: A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1–77.04, P < 0.00001; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10–1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14–2.31, P = 0.007; I2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23–1.36, P = 0.20; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52–2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63–1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44–1.51, P = 0.52; I2 = 25%; low certainty) between the two groups. Conclusions: Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload. Systematic Review Registration: This systematic review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), registration number CRD498330. [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) is a common cause of hospitalization, particularly among older individuals, and has high mortality and readmission rates. Adherence to guideline-directed medical therapy (GDMT) is crucial for improving outcomes in heart failure (HF) patients, as non-adherence can lead to exacerbations and adverse outcomes. However, studies have shown that medication non-adherence rates among HF patients can be as high as 70%. Various factors contribute to non-adherence, including patient circumstances, treatment-related factors, and healthcare system and payer factors. Adherence interventions, such as patient education, medication regimen management, and reminders, have been shown to improve medication adherence and reduce mortality and hospital readmissions in HF patients. Improving adherence to GDMT is essential for improving AHF outcomes, and further research is needed to identify effective approaches to enhance medication adherence. [Extracted from the article]

The article discusses the EMPULSE trial, which investigated the efficacy of early initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors, specifically empagliflozin, in hospitalized heart failure (HF) patients. The trial enrolled 530 patients with HF symptoms, regardless of left ventricular ejection fraction (LVEF), and randomized them to receive either empagliflozin or a placebo. The results showed that empagliflozin had clinical benefits and a similar safety profile compared to the placebo, regardless of baseline LVEF. This analysis adds to the growing evidence supporting the early initiation and rapid up-titration of guideline-directed medical therapy (GDMT) in HF patients. [Extracted from the article]

The article discusses the Patient-Centered Care Transitions in Heart Failure (PACT-HF) randomized controlled trial, which aimed to improve medication adherence in heart failure patients. The study found that transitional care programs, which focus on coordinating care between inpatient and outpatient settings, did not significantly improve the uptake of guideline-directed medical therapy (GDMT) medications. The authors suggest that future interventions should prioritize medication initiation and titration immediately after a heart failure exacerbation, and that successful interventions should have a high intensity and duration to drive behavior change in both physicians and patients. Overall, the study highlights the need for further research to develop effective transitional care programs for heart failure patients. [Extracted from the article]

Adults with chronic kidney disease (CKD) are at increased risk for developing heart failure (HF). However, longitudinal cardiac remodeling in CKD has not been well-characterized and its association with HF outcomes remains unknown. We evaluated the association between change in echocardiographic parameters between baseline and year 4 with the subsequent risk of HF hospitalization and death using Cox proportional hazard models in a landmark analysis of a prospective multicenter CKD cohort. Among 2673 participants, mean ± SD age was 61 ± 11 years, with 45% women, and 56% non-white. A total of 472 hospitalizations for HF and 776 deaths occurred during a median (interquartile range) follow-up duration of 8.0 (6.3–9.1) years. Patients hospitalized for HF experienced larger preceding absolute increases in left ventricular (LV) volumes and decreases in LV ejection fraction. Adverse changes in LV ejection fraction, LV cavity volume, LV mass index, and LV geometry were independently associated with an increased risk of HF hospitalization and death. Among adults with CKD, deleterious cardiac remodeling occurs over a relatively short timeframe and adverse remodeling is associated with increased risk of HF-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Aims: There is considerable variability in the effect of intravenous iron on hard cardiovascular (CV)‐related outcomes in patients with heart failure (HF) in randomized controlled trials (RCTs). We use a meta‐analytic approach to analyse data from existing RCTs to derive a more robust estimate of the effect size of intravenous iron infusion on CV‐related outcomes in patients with HF. Method and results: PubMed/Medline was searched using the following terms: ('intravenous' and 'iron' and 'heart failure') from inception till 6 November 2022 for RCTs comparing intravenous iron infusion with placebo or standard of care in patients with HF and iron deficiency. Outcomes were the composite of CV mortality and first hospitalization for HF; all‐cause mortality; CV mortality; first hospitalization for HF; and total hospitalizations for HF. Random effects risk ratio (RR) with 95% confidence intervals (CIs) were calculated. Ten RCTs with a total of 3438 patients were included. Intravenous iron resulted in a significant reduction in the composite of CV mortality and first hospitalization for HF [RR 0.0.85; 95% CI (0.77, 0.95)], first hospitalization for HF [RR 0.82; 95% CI (0.67, 0.99)], and total hospitalizations for HF [RR 0.74; 95% CI (0.60, 0.91)] but no statistically significant difference in all‐cause mortality [RR 0.95; 95% CI. (0.83, 1.09)] or CV mortality [OR 0.89; 95% CI (0.75, 1.05)]. Conclusions: Intravenous iron infusion in patients with HF reduces the composite risk of first hospitalization for HF and CV mortality as well as the risks of first and recurrent hospitalizations for HF, with no effect on all‐cause mortality or CV mortality alone. [ABSTRACT FROM AUTHOR]

Aims: Low serum albumin levels are associated with poor prognosis in numerous chronic disease states but the relationship between albumin and outcomes in patients with heart failure (HF) and secondary mitral regurgitation (SMR) has not been described. Methods and results: The randomized COAPT trial evaluated the safety and effectiveness of transcatheter edge‐to‐edge repair (TEER) with the MitraClipTM plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate‐to‐severe or severe SMR. Baseline serum albumin levels were measured at enrolment. Among 614 patients enrolled in COAPT, 559 (91.0%) had available baseline serum albumin levels (median 4.0 g/dl, interquartile range 3.7–4.2 g/dl). Patients with albumin <4.0 g/dl compared with ≥4.0 g/dl were older and more likely to have ischaemic cardiomyopathy and a hospitalization within the year prior to enrolment. After multivariable adjustment, patients with albumin <4.0 g/dl had higher 4‐year rates of all‐cause death (63.7% vs. 47.6%; adjusted hazard ratio 1.34, 95% confidence interval 1.02–1.74; p = 0.032), but there were no significant differences in HF hospitalizations (HFH) or all‐cause hospitalizations according to baseline serum albumin level. The relative effectiveness of TEER plus GDMT versus GDMT alone was consistent in patients with low and high albumin levels (pinteraction = 0.19 and 0.35 for death and HFH, respectively). Conclusion: Low baseline serum albumin levels were independently associated with reduced 4‐year survival in patients with HF and severe SMR enrolled in the COAPT trial, but not with HFH. Patients treated with TEER derived similarly robust reductions in both death and HFH regardless of baseline albumin level. [ABSTRACT FROM AUTHOR]

The coronavirus 2019 (COVID‐19) infection pandemic has affected the care of patients with heart failure (HF). Several consensus documents describe the appropriate diagnostic algorithm and treatment approach for patients with HF and associated COVID‐19 infection. However, few questions about the mechanisms by which COVID can exacerbate HF in patients with high‐risk (Stage B) or symptomatic HF (Stage C) remain unanswered. Therefore, the type of HF occurring during infection is poorly investigated. The diagnostic differentiation and management should be focused on the identification of the HF phenotype, underlying causes, and subsequent tailored therapy. In this framework, the relationship existing between COVID and onset of acute decompensated HF, isolated right HF, and cardiogenic shock is questioned, and the specific management is mainly based on local hospital organization rather than a standardized model. Similarly, some specific populations such as advanced HF, heart transplant, patients with left ventricular assist device (LVAD), or valve disease remain under investigated. In this systematic review, we examine recent advances regarding the relationships between HF and COVID‐19 pandemic with respect to epidemiology, pathogenetic mechanisms, and differential diagnosis. Also, according to the recent HF guidelines definition, we highlight different clinical profile identification, pointing out the main concerns in understudied HF populations. [ABSTRACT FROM AUTHOR]

Although electrolyte abnormalities and acute kidney injury are often a barrier to adequate decongestion therapy, acetazolamide may be safely added to loop diuretics with proactive monitoring and electrolyte repletion. ADVOR is a rigorous randomized controlled trial establishing acetazolamide as both a safe and effective adjunct to standard decongestion therapy for ADHF. At 3 days, 42.2% in the acetazolamide group reached the primary endpoint (i.e. successful decongestion) compared to 30.5% of patients in the placebo group (risk ratio [RR] 1.46, 95% confidence interval [CI] 1.17-1.82; I p i < 0.001), and length of stay was 1.1 days shorter in the acetazolamide group (9.9 vs. 8.8 days; RR 0.89, 95% CI 0.81-0.98; I p i = 0.02). [Extracted from the article]

In conclusion, Chatur I et al i . capture a deeper spectrum of hospitalization of HF in the context of pooled data from large HF clinical trials. Unsurprisingly, patients experiencing complicated HF hospitalizations were at significantly higher risk for in-hospital mortality compared with those with uncomplicated hospitalizations in both DELIVER (16.7% vs. 2.3%) and DAPA-HF (15.1% vs. 3.8%). While the traditional focus of therapeutics has been to reduce HF hospitalizations, recent insights and methodological advances have broadened our perspectives on endpoint selection in HF trials. [Extracted from the article]

Purpose of Review: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection. Recent Findings: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Summary: Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications. [ABSTRACT FROM AUTHOR]

Aims: Hospitalization for heart failure (HF) constitutes a major healthcare and economic burden. Trends and characteristics of hospitalizations for HF for the recent years are not clear. We sought to determine the trends and characteristics of hospitalization for HF in the United States. Method and results: A retrospective analysis of the National Inpatient Sample weighted data between 1 January 2004 and 31 December 2018, which included hospitalized adults ≥ 18 years with primary discharge diagnosis of HF using International Classification of Diseases‐9/10 administrative codes. Main outcomes were trends in hospitalizations for HF (per 1000 person) and inpatient mortality (%) between 2004 and 2018. Conclusions: Hospitalizations for HF have been increasing across both sexes and age groups since 2013, whereas inpatient mortality has been decreasing over the study period. Blacks have the highest risk of hospitalization for HF, and Whites have the highest in‐hospital mortality. There are significant racial and geographic disparities related to hospitalizations for HF. [ABSTRACT FROM AUTHOR]

Inadequate at-home management and self-awareness of heart failure (HF) exacerbations are known to be leading causes of the greater than 1 million estimated HF-related hospitalizations in the USA alone. Most current at-home HF management protocols include paper guidelines or exploratory health applications that lack rigor and validation at the level of the individual patient. We report on a novel triage methodology that uses machine learning predictions for real-time detection and assessment of exacerbations. Medical specialist opinions on statistically and clinically comprehensive, simulated patient cases were used to train and validate prediction algorithms. Model performance was assessed by comparison to physician panel consensus in a representative, out-of-sample validation set of 100 vignettes. Algorithm prediction accuracy and safety indicators surpassed all individual specialists in identifying consensus opinion on existence/severity of exacerbations and appropriate treatment response. The algorithms also scored the highest sensitivity, specificity, and PPV when assessing the need for emergency care. Lay summary: Here we develop a machine-learning approach for providing real-time decision support to adults diagnosed with congestive heart failure. The algorithm achieves higher exacerbation and triage classification performance than any individual physician when compared to physician consensus opinion. [ABSTRACT FROM AUTHOR]

Background: The impact of the novel coronavirus disease 2019 (COVID‐19) pandemic on diet and nutrition among older adults with chronic medical conditions have not been well‐described. Methods: We conducted a survey addressing (1) food access, (2) diet quality and composition, (3) nutritional understanding, and (4) attitudes towards research among adults with heart failure (HF) within an integrated health system. Adults (≥18 years) with diagnosed HF and at least one prior hospitalization for HF within the last 12 months were approached to complete the survey electronically or by mail. Outcomes included all‐cause and HF‐specific hospitalizations and all‐cause death was ascertained via the electronic health record. Results: Among 1212 survey respondents (32.5% of eligible patients) between May 18, 2020 and September 30, 2020, mean ± SD age was 77.9 ± 11.4 years, 50.1% were women, and median (25th–75th) left ventricular ejection fraction was 55% (40%–60%). Overall, 15.1% of respondents were food insecure, and only 65% of participants answered correctly more than half of the items assessing nutritional knowledge. Although most respondents were willing to participate in future research, that number largely declined for studies requiring blood draws (32.2%), study medication (14.4%), and/or behavior change (27.1%). Food security, diet quality, and nutritional knowledge were not independently associated with outcomes at 90 or 180 days. Conclusion: In a cohort of older adults with HF and multiple comorbidities, a significant proportion reported issues with food access, diet quality, and nutritional knowledge during the COVID‐19 pandemic. Future research should evaluate interventions targeting these domains in at‐risk individuals. Key points: Upwards of 15% of respondents screened positive for food insecurity, and only approximately 65% of respondents answered more than half of the items correctly on a questionnaire assessing nutritional understanding.Although the majority of respondents indicated that would be willing to consider participating in future research, that proportion declined markedly for studies requiring blood draws, study drugs, and/or behavior change.None of the functional domains assessed by this survey were independently associated with clinical outcomes in our cohort. [ABSTRACT FROM AUTHOR]

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large phenotypic variability in CS, as a result of the diverse aetiologies, pathogenetic mechanisms, haemodynamics, and stages of severity. Although early revascularization remains the most important intervention for CS in settings of acute myocardial infarction, the administration of timely and effective antithrombotic therapy is critical to improving outcomes in these patients. In addition, other clinical settings or non‐acute myocardial infarction aetiologies, associated with high thrombotic risk, may require specific regimens of short‐term or long‐term antithrombotic therapy. In CS, altered tissue perfusion, inflammation, and multi‐organ dysfunction induce unpredictable alterations to antithrombotic drugs' pharmacokinetics and pharmacodynamics. Other interventions used in the management of CS, such as mechanical circulatory support, renal replacement therapies, or targeted temperature management, influence both thrombotic and bleeding risks and may require specific antithrombotic strategies. In order to optimize safety and efficacy of these therapies in CS, antithrombotic management should be more adapted to CS clinical scenario or specific device, with individualized antithrombotic regimens in terms of type of treatment, dose, and duration. In addition, patients with CS require a close and appropriate monitoring of antithrombotic therapies to safely balance the increased risk of bleeding and thrombosis. [ABSTRACT FROM AUTHOR]

Purpose of the Review: In the decades following the advent of percutaneous coronary intervention, the optimal treatment strategy for managing stable ischemic heart disease has remained a topic of debate. The purpose of this review is to discuss current literature that provides insight into preferred treatment strategies for managing stable coronary artery disease. Recent Findings: The COURAGE trial (2007) compared patients with stable coronary artery disease treated with percutaneous coronary intervention plus optimal medical therapy versus optimal medical therapy alone and found no difference in death from any cause and non-fatal myocardial infarction at 4.6 years. The more recent ISCHEMIA trial (2020) compared an initial invasive revascularization strategy with optimal medical therapy to optimal medical therapy alone and similarly found no difference in death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest at 5 years. Summary: When applied to a broad population with stable coronary artery disease, evidence suggests there is no benefit to an initial invasive revascularization strategy relative to optimal medical therapy alone. Further investigation is warranted to determine whether there are subgroups of individuals that may benefit from earlier revascularization. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury is a common complication of percutaneous coronary intervention and has been associated with an increased risk of death and progressive chronic kidney disease. However, whether the timing of acute kidney injury after urgent percutaneous coronary intervention could be used to improve patient risk stratification is not known.Methods: We conducted a retrospective cohort study in adults surviving an urgent percutaneous coronary intervention between 2008 and 2013 within Kaiser Permanente Northern California, a large integrated healthcare delivery system, to evaluate the impact of acute kidney injury during hospitalization at 12 (±6), 24 (±6) and 48 (±6) hours after urgent percutaneous coronary intervention and subsequent risks of adverse outcomes within the first year after discharge. We used multivariable Cox proportional hazards models with adjustment for a high-dimensional propensity score for developing acute kidney injury after percutaneous coronary intervention to examine the associations between acute kidney injury timing and all-cause death and worsening chronic kidney disease.Results: Among 7250 eligible adults undergoing urgent percutaneous coronary intervention, 306 (4.2%) had acute kidney injury at one or more of the examined time periods after percutaneous coronary intervention. After adjustment, acute kidney injury at 12 (±6) hours was independently associated with higher risks of death (adjusted hazard ratio [aHR] 3.55, 95% confidence interval [CI] 2.19-5.75) and worsening kidney function (aHR 2.40, 95% CI:1.24-4.63). Similar results were observed for acute kidney injury at 24 (±6) hours and death (aHR 3.90, 95% CI:2.29-6.66) and worsening chronic kidney disease (aHR 4.77, 95% CI:2.46-9.23). Acute kidney injury at 48 (±6) hours was associated with excess mortality (aHR 1.97, 95% CI:1.19-3.26) but was not significantly associated with worsening kidney function (aHR 0.91, 95% CI:0.42-1.98).Conclusions: Timing of acute kidney injury after urgent percutaneous coronary intervention may be differentially associated with subsequent risk of worsening kidney function but not death. [ABSTRACT FROM AUTHOR]

Aims: Associations between growth differentiation factor‐15 (GDF‐15), cardiovascular outcomes, and exercise capacity among patients with a recent hospitalization for heart failure (HHF) and heart failure with reduced ejection fraction (HFrEF) are unknown. We utilized data from the 'Functional Impact of GLP‐1 for Heart Failure Treatment' (FIGHT) study to address these knowledge gaps. Methods and results: FIGHT was a randomized clinical trial testing the effect of liraglutide (vs. placebo) among 300 participants with HFrEF and a recent HHF. Multivariable regression models evaluated associations between baseline GDF‐15 and change in GDF‐15 (per 1000 pg/mL increase from baseline to 30 days) with clinical outcomes (at 180 days) and declines in exercise capacity (6 min walk distance ≥ 45 m). At baseline (n = 249), median GDF‐15 value was 3221 pg/mL (interquartile range 1938–5511 pg/mL). Participants in the highest tertile of baseline GDF‐15 were more likely to be male and have more co‐morbidities. After adjustment, an increase in GDF‐15 over 30 days was associated with higher risk of death or HHF [hazard ratio 1.35, 95% confidence interval (CI) 1.11–1.64]. In addition, higher baseline GDF‐15 (per 1000 pg/mL until 6000 pg/mL) and an increase in GDF‐15 over 30 days were associated with declining 6 min walk distance (odds ratio 1.26, 95% CI 1.02–1.55 and odds ratio 1.37, 95% CI 1.12–1.69, respectively). GDF‐15 levels remained stable among participants randomized to liraglutide. Conclusions: An increase in GDF‐15 over 30 days among patients in HFrEF was independently associated with an increased risk of cardiovascular events and declining exercise capacity. These results support the value of longitudinal GDF‐15 trajectory in informing risk of heart failure disease progression. [ABSTRACT FROM AUTHOR]

These data strongly suggest that patients at risk of AHF, i.e. those with chronic HF with reduced ejection fraction and/or other cardiovascular diseases, should be heavily treated in order to prevent death when exposed to future AHF hospitalization. The study also confirms that despite the favourable trends in AHF survival in the past decades, death after AHF remained high, with one quarter of AHF patients dying in the following year. [Extracted from the article]

Aims: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition, and tissue congestion manifested by oedema is not present in all patients. We compared clinical characteristics, exercise capacity, and outcomes in patients with HFpEF with and without oedema. Methods and results: This study was a post hoc analysis of pooled data of patients with left ventricular ejection fraction of ≥50% enrolled in the DOSE, CARRESS‐HF, RELAX, ATHENA, ROSE, INDIE, and NEAT trials. Patients were dichotomized by the severity of oedema. Cox proportional hazard regression and generalized linear regression models were used to assess associations between oedema, symptoms, and clinical outcomes. The ambulatory cohort included 393 patients (228 with and 165 without oedema), and the hospitalized cohort included 338 patients (249 with ≥moderate oedema and 89 with mild or none). Among ambulatory patients, patients with oedema had a higher body mass index (35.2 kg/m2 [inter‐quartile range, IQR 30.5, 41.6] vs. 31.6 kg/m2 [IQR 27.9, 36.3], P < 0.001), greater burden of co‐morbidities, higher intravascular pressures estimated on physical examination (elevated jugular venous pressure: 50% vs. 24.7%, P < 0.001), poorer renal function (creatinine: 1.2 mg/dL [IQR 0.9, 1.5] vs. 1 mg/dL [IQR 0.8, 1.3], P = 0.003), and lower peak VO2 (adjusted mean difference −1.04 mL/kg/min, 95% confidence interval [−1.71, −0.37], P < 0.003). Among hospitalized patients, despite greater in‐hospital fluid/weight loss in the ≥moderate oedema group, there was no difference in the improvement in dyspnoea by the visual analogue scale or well‐being visual analogue scale from baseline to 3–4 days and no statistically significant difference in the rate of 60 day rehospitalization/death (adjusted hazard ratio 1.44, 95% confidence interval [0.87, 2.39], P = 0.156). Conclusions: Patients with HFpEF and oedema display higher body mass, greater burden of co‐morbidities, and more severe exercise intolerance, but clinical responses to treatment appear similar. Further research is required to better understand the nature of volume distribution in different HFpEF phenotypes. [ABSTRACT FROM AUTHOR]

Background: Prediction of readmission and death after hospitalization for heart failure (HF) is an unmet need. Aim: We evaluated the ability of clinical parameters, NT-proBNP level and noninvasive lung impedance (LI), to predict time to readmission (TTR) and time to death (TTD). Methods and Results: The present study is a post hoc analysis of the IMPEDANCE-HF extended trial comprising 290 patients with LVEF ≤45% and New York Heart Association functional class II–IV, randomized 1:1 to LI-guided or conventional therapy. Of all patients, 206 were admitted 766 times for HF during a follow-up of 57 ± 39 months. The normal LI (NLI), representing the "dry" lung status, was calculated for each patient at study entry. The current degree of pulmonary congestion (PC) compared with its dry status was represented by ΔLIR = ([measured LI/NLI] – 1) × 100%. Twenty-six parameters recorded during HF admission were used to predict TTR and TTD. To determine the parameter which mainly impacted TTR and TTD, variables were standardized, and effect size (ES) was calculated. Multivariate analysis by the Andersen-Gill model demonstrated that ΔLIRadmission (ES = 0.72), ΔLIRdischarge (ES = –3.14), group assignment (ES = 0.2), maximal troponin during HF admission (ES = 0.19), LVEF related to admission (ES = –0.22) and arterial hypertension (ES = 0.12) are independent predictors of TTR (p < 0.01, χ2 = 1,206). Analysis of ES showed that residual PC assessed by ∆LIRdischarge was the most prominent predictor of TTR. One percent improvement in predischarge PC, assessed by ∆LIRdischarge, was associated with a likelihood of TTR increase by 14% (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.13–1.15, p < 0.01) and TTD increase by 8% (HR 1.08, 95% CI 1.07–1.09, p < 0.01). Conclusion: The degree of predischarge PC assessed by ∆LIR is the most dominant predictor of TTR and TTD. [ABSTRACT FROM AUTHOR]

Patients hospitalized for heart failure (HF) remain at high risk for early readmission. A post hoc analysis was performed of the biomarker substudy of the ASCEND-HF trial. An in-hospital congestion score was derived using orthopnea, pedal edema, and NT-proBNP levels. Its added prognostic value beyond traditional risk factors was assessed by determining the net reclassification index (NRI). Study participants (n = 884) had a median age (years) of 67 (55–77), 68% were male, and the median (25th–75th) ejection fraction (%) was 26 (20–40). After adjustment, increasing congestion score was associated with 30-day all-cause mortality or HF hospitalization (odds ratio = 1.51, 95% confidence interval [CI] 1.28–1.77, p < 0.001) and 180-day all-cause mortality (hazard ratio = 1.48, 95% CI 1.28–1.72, p < 0.001). However, adding the congestion score to the multivariable model did not significantly impact the NRI. A higher in-hospital congestion score portended a poor short-term prognosis but did not significantly reclassify risk. [ABSTRACT FROM AUTHOR]

Aims: Worsening heart failure (HF) is associated with shorter left ventricular systolic ejection time (SET), but there are limited data describing the relationship between SET and clinical outcomes. Thus, the objective was to describe the association between SET and clinical outcomes in an ambulatory HF population irrespective of ejection fraction (EF).Methods and Results: We identified ambulatory patients with HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) who had an outpatient transthoracic echocardiogram performed between August 2008 and July 2010 at a tertiary referral centre. Multivariable logistic regression was used to evaluate the association between SET and 1-year outcomes. A total of 545 HF patients (171 HFrEF, 374 HFpEF) met eligibility criteria. Compared with HFpEF, HFrEF patients were younger [median age 60 years (25th-75th percentiles 50-69) vs. 64 years (25th-75th percentiles 53-74], with fewer females (30% vs. 56%) and a similar percentage of African Americans (36% vs. 35%). Median (25th-75th percentiles) EF with HFrEF was 30% (25-35%) and with HFpEF was 54% (48-58%). Median SET was shorter (280 ms vs. 315 ms, P < 0.001), median pre-ejection period was longer (114 ms vs. 89 ms, P < 0.001), and median relaxation time was shorter (78.7 ms vs. 93.3 ms, P < 0.001) among patients with HFrEF vs. HFpEF. Death or HF hospitalization occurred in 26.9% (n = 46) HFrEF and 11.8% (n = 44) HFpEF patients. After adjustment, longer SET was associated with lower odds of the composite of death or HF hospitalization at 1 year among HFrEF but not HFpEF patients.Conclusion: Longer SET is independently associated with improved outcomes among HFrEF patients but not HFpEF patients, supporting a potential role for normalizing SET as a therapeutic strategy with systolic dysfunction. [ABSTRACT FROM AUTHOR]

Aims: Non-cardiac comorbidities are highly prevalent in patients with heart failure (HF). Our objective was to define the association between non-cardiac comorbidity burden and clinical outcomes, costs of care, and length of stay within a large randomized trial of acute HF patients.Methods and Results: Patients with complete medical history for the following comorbidities were included: diabetes mellitus, chronic obstructive pulmonary disease, chronic liver disease, history of cancer within the last 5 years, chronic renal disease (baseline serum creatinine >3.0 mg/mL), current smoking, alcohol abuse, depression, anaemia, peripheral arterial disease, and cerebrovascular disease. Patients were classified by overall burden of non-cardiac comorbidities (0, 1, 2, 3, and 4+). Hierarchical generalized linear models were used to assess associations between comorbidity burden and 30-day all-cause death or HF hospitalization and 180-day all-cause death in addition to costs of care and length of stay. A total of 6945 patients were included in the final analysis. Mean comorbidity number was 2.2 (± 1.34). Patients with 4+ comorbidities had higher rates of 30-day all-cause death/HF hospitalization as compared with patients with no comorbidities [odds ratio (OR) 3.32, 95% confidence interval (CI) 1.61-6.84; P < 0.01]. Similar results were seen with respect to 180-day death (OR 2.13, 95% CI 1.33-3.43; P < 0.01). Higher comorbidity burden was associated with higher 180-day costs of care and length of stay.Conclusions: Higher comorbidity burden is associated with poor clinical outcomes, higher costs of care, and extended length of stay. Further studies are needed to define the impact of comorbidity management programmes on outcomes for HF patients. [ABSTRACT FROM AUTHOR]

Aims: Implantable cardioverter-defibrillator (ICD) therapy reduces mortality in patients with heart failure and current guidelines advise implantation of ICDs in patients with a life expectancy of >1 year. We examined trends in all-cause mortality in patients who underwent primary or secondary prevention ICD placement in the Veterans Affairs (VA) Health System.Methods and Results: US veterans receiving a new ICD placement for primary or secondary prevention of sudden cardiac death between January 2007 and January 2015, who had heart failure with reduced ejection fraction (HFrEF) were included in the analysis. We assessed all-cause mortality 1 year post-ICD implantation. ICD implantation and HFrEF diagnosis were established with associated ICD-9 codes. The VA death registry was utilized to identify mortality rates following ICD placement. Results were subsequently age-stratified. There were 17 901 veterans with HFrEF with ICD placement nationwide. There was no statistically significant difference in 1-year mortality from 2007 (13.1%) to 2014 (13.4%, P > 0.05). There was a significant increase in 1-year mortality in patients in the oldest age quartile (81.6 years, 32.3% mortality) compared to the youngest quartile (55.5 years, 7% mortality). The finding of diverging clinical outcomes extended to the 30-day but also 8-year mark.Conclusions: Our data suggest there is a high 1-year mortality in aging HFrEF patients undergoing primary and secondary prevention ICD placement. This highlights the importance of developing better predictive models for mortality in our ICD eligible patient population. [ABSTRACT FROM AUTHOR]

B This article refers to 'Liver tests, cardiovascular outcomes and effects of empagliflozin in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved trial' by M. Böhm I et al i ., published in this issue on pages 1375-1383. b Heart failure (HF) is a global epidemic affecting more than 64 million people worldwide.[1] Acute and chronic liver injury, as evidenced by elevations in liver function tests (LFTs) are a common manifestation of acute and chronic HF and may reflect systemic hypoperfusion or chronic passive, venous congestion, respectively.[2] Several recently published reports have demonstrated the potential utility of LFTs in HF prognostication.[[3], [5], [7], [9], [11]] Specifically, reduced levels of albumin and elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase (ALP) have traditionally been associated with increased mortality and HF hospitalizations.[[3], [5], [7], [9], [11]] However, these prior studies examined the role of LFTs in those with acute HF irrespective of left ventricular ejection fraction (LVEF) or ambulatory HF with reduced ejection fraction (HFrEF). The authors excluded patients based on abnormal LFTs (see definition above), which may not completely capture patients with underlying liver disease. In conclusion, Böhm I et al i .[12] enhance the current understanding of the prognostic implications of LFTs in HF and provide new insights into the associations between elevated LFTs and ambulatory HFmrEF/HFpEF. [Extracted from the article]