Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve blood glucose control by blocking renal glucose reabsorption with little subsequent risk of hypoglycemia. Consequently, there are decreases in plasma volume, body weight, and blood pressure. Additional putative benefits include improved cardiovascular energetics, decreased systemic inflammation, and less renal dysfunction. Multiple cardiovascular outcome trials in diabetic patients have demonstrated this drug class reduces the risk of adverse cardiovascular events. Reductions in heart failure (HF) hospitalization suggested that SGLT2 inhibitors might prove useful for the primary treatment of HF. Two large subsequent trials studying SGLT2 inhibitors in heart failure with reduced ejection fraction (HFrEF) demonstrated a reduction in cardiovascular mortality, HF hospitalizations, and renal-specific adverse events. This medication class is now recognized as a new pillar of therapy for patients with HFrEF. The cardiovascular and HF community await the results of ongoing trials of SGLT2 inhibition in patients with HF with preserved ejection fraction.

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

Bridge-to-transplant temporary mechanical circulatory support and risk of allosensitization.

INTRODUCTION: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. METHODS: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. RESULTS: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028. CONCLUSIONS: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support.

The "Microplastome" - A Holistic Perspective to Capture the Real-World Ecology of Microplastics.

Microplastic pollution, an emerging pollution issue, has become a significant environmental concern globally due to its ubiquitous, persistent, complex, toxic, and ever-increasing nature. As a multifaceted and diverse suite of small plastic particles with different physicochemical properties and associated matters such as absorbed chemicals and microbes, future research on microplastics will need to comprehensively consider their multidimensional attributes. Here, we introduce a novel, conceptual framework of the "microplastome", defined as the entirety of various plastic particles (<5 mm), and their associated matters such as chemicals and microbes, found within a sample and its overall environmental and toxicological impacts. As a novel concept, this paper aims to emphasize and call for a collective quantification and characterization of microplastics and for a more holistic understanding regarding the differences, connections, and effects of microplastics in different biotic and abiotic ecosystem compartments. Deriving from this lens, we present our insights and prospective trajectories for characterization, risk assessment, and source apportionment of microplastics. We hope this new paradigm can guide and propel microplastic research toward a more holistic era and contribute to an informed strategy for combating this globally important environmental pollution issue.

Pharmaceutical Residues in Edible Oysters along the Coasts of the East and South China Seas and Associated Health Risks to Humans and Wildlife.

The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.

Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association.

Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

Interrupted Time Series Analysis of Donor Heart Use Before and After the 2018 UNOS Heart Allocation Policy Change.

BACKGROUND: Donor heart scarcity remains the fundamental barrier to increased transplant access. We examined whether 2018 United Network for Organ Sharing (UNOS) policy changes have had an impact on donor heart acceptance rates. METHODS AND RESULTS: We performed an interrupted time series analysis in UNOS to evaluate for abrupt changes in donor heart-acceptance rates associated with the new policy. All adult donor offers were evaluated between 2015 and 2021 (n = 66,654 donors). Donor volumes and transplants increased during this period, but the donor acceptance rate declined significantly from 31% in quarter 3 of 2018 to 26% acceptance in quarter 3 of 2021 (slope change -0.4% per quarter; P < 0.001). We identified 2 trends associated with this decline: (1) a growing number of donors with high-risk features, and (2) decreased acceptance of donors with certain high-risk features in the new allocation system. CONCLUSIONS: Heart transplant volumes have increased in recent years as a result of increased donor volumes, but donor heart acceptance rates began decreasing under the current allocation system. Changes in the donor pool and acceptance patterns for certain donor-risk features may explain this shift and warrant further evaluation to maximize donor heart use.

Simultaneous Dissemination of Nanoplastics and Antibiotic Resistance by Nematode Couriers.

Nanoplastics (NPs) are increasingly recognized as a newly emerging pollutant in the environment. NPs can enable the colonization of microbial pathogens on their surfaces and adsorb toxic pollutants, such as heavy metals and residual antibiotics. Although the dissemination of plastic particles in water bodies and the atmosphere is widely studied, the dissemination of NPs and adsorbed pollutants on land, via biological means, is poorly understood. Since soil animals, such as the bacterivorous nematode Caenorhabditis elegans (C. elegans), are highly mobile, this raises the possibility that they play an active role in disseminating NPs and adsorbed pollutants. Here, we established that antibiotic-resistant bacteria could aggregate with antibiotic-adsorbed NPs to form antibiotic-adsorbed NP-antibiotic resistant bacteria (ANP-ARB) aggregates, using polymyxins (colistin) as a proof-of-concept. Colistin-resistant mcr-1 bearing Escherichia coli from a mixed population of resistant and sensitive bacteria selectively aggregate with colistin-ANPs. In the soil microcosm, C. elegans fed on ANP-ARB clusters, resulting in the rapid spread of ANP-ARB by the nematodes across the soil at a rate of 40-60 cm per day. Our work revealed insights into how NPs could still disseminate across the soil faster than previously thought by "hitching a ride" in soil animals and acting as agents of antibiotic-resistant pathogens and antibiotic contaminants. This poses direct risks to ecology, agricultural sustainability, and human health.

Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial.

AIM: Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF). METHODS AND RESULTS: The GALACTIC-HF enrolled patients with baseline SBP ≥85 mmHg with a primary outcome of time to cardiovascular death or first heart failure event. In this analysis, patients were divided according to their baseline SBP (≤100 vs. >100 mmHg). Among the 8232 analysed patients, 1473 (17.9%) had baseline SBP ≤100 mmHg and 6759 (82.1%) had SBP >100 mmHg. The primary outcome occurred in 715 (48.5%) and 2415 (35.7%) patients with SBP ≤100 and >100 mmHg, respectively. Patients with lower SBP were at higher risk of adverse outcomes. Omecamtiv mecarbil, compared with placebo, appeared to be more effective in reducing the primary composite endpoint in patients with SBP ≤100 mmHg [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.94] compared with those with SBP >100 mmHg (HR, 0.95; 95% CI, 0.88-1.03; P-value for interaction = 0.051). In both groups, omecamtiv mecarbil did not change SBP values over time and did not increase the risk of adverse events, when compared with placebo. CONCLUSION: In GALACTIC-HF, risk reduction of heart failure outcomes with omecamtiv mecarbil compared with placebo was large and significant in patients with low SBP. Omecamtiv mecarbil did not affect SBP and was well tolerated independent of SBP values.

Hemodynamics for the Heart Failure Clinician: A State-of-the-Art Review.

Heart failure (HF) fundamentally reflects an inability of the heart to provide adequate blood flow to the body without incurring the cost of increased cardiac filling pressures. This failure occurs first during the stressed state, but progresses until hemodynamic derangements become apparent at rest. As such, the measurement and interpretation of both resting and stressed hemodynamics serve an integral role in the practice of the HF clinician. In this review, we discuss conceptual and technical best practices in the performance and interpretation of both resting and invasive exercise hemodynamic catheterization, relate important pathophysiologic concepts to clinical care, and discuss updated, evidence-based applications of hemodynamics as they pertain to the full spectrum of HF conditions.

Metolazone Versus Intravenous Chlorothiazide for Decompensated Heart Failure Sequential Nephron Blockade: A Retrospective Cohort Study.

BACKGROUND: Metolazone and intravenous (IV) chlorothiazide are commonly used diuretics for sequential nephron blockade (SNB) in patients with acute decompensated heart failure (ADHF). Previous studies suggest metolazone may be comparable with chlorothiazide in terms of efficacy and safety. The objective of this study was to determine whether IV chlorothiazide is superior to metolazone in increasing net urine output (UOP) of hospitalized patients with ADHF. METHODS AND RESULTS: This retrospective cohort study included hospitalized patients with ADHF and evidence of loop diuretic resistance in a tertiary academic medical center. The primary end point was the change in net 24-hour UOP in patients treated with IV chlorothiazide compared with metolazone. The relative cost of chlorothiazide doses and metolazone doses administered during SNB was a notable secondary end point. The median change in net 24-hour UOP in the IV chlorothiazide group was -1481.9 mL (interquartile range -2696.0 to -641.0 mL) and -1780.0 mL (interquartile range -3084.5 to -853.5 mL) in the metolazone group (P = .05) across 220 hospital encounters. The median cost of chlorothiazide and metolazone doses used during SNB was $360 and $4, respectively (P < .01). CONCLUSIONS: Chlorothiazide was not superior to metolazone in changing the net 24-hour UOP of patients with ADHF and loop resistance. Preferential metolazone use in SNB is a potential cost-saving measure.

Outcomes in Patients With Chronic Kidney Disease and End-stage Renal Disease and Durable Left Ventricular Assist Device: Insights From the United States Renal Data System Database.

BACKGROUND: There is paucity of data regarding durable left ventricular assist device (LVAD) outcomes in patients with chronic kidney disease (CKD) stages 3-5 and CKD stage 5 on dialysis (end-stage renal disease [ESRD]). METHODS AND RESULTS: We conducted a retrospective study of Medicare beneficiaries with ESRD and a 5% sample of patients with CKD with an LVAD (2006-2018) to determine 1-year outcomes using the United States Renal Data System database. The LVAD implantation, comorbidities, and outcomes were identified using appropriate International Classification of Diseases, 9th and 10th edition codes. We identified 496 patients with CKD and 95 patients with ESRD who underwent LVAD implantation. The patients with ESRD were younger (59 years vs 66 years; P < .001), had more Blacks (40% vs 24.6%, P = .009), compared with the CKD group. The 1-year mortality (49.5% vs 30.9%, P < .001) and index mortality (27.4% vs 16.7%, P = .014) rates were higher for patients with ESRD. A subgroup analysis showed significantly higher mortality in ESRD vs CKD 3 (49.5% vs 30.2%, adjusted P = .009), but no significant difference in mortality between stage 3 vs 4/5 (30.2% vs 30.8%, adjusted P = .941). There was no significant difference in secondary outcomes (bleeding, stroke, and sepsis/infection) during follow-up between the 2 groups. CONCLUSIONS: Patients with ESRD undergoing LVAD implantation had significantly higher index and 1-year mortality rates compared with patients with CKD.

Quantifying the Impact of Atrial Fibrillation on Heart Failure-Related Patient-Reported Outcomes in the Utah mEVAL Program.

BACKGROUND: Atrial fibrillation (AF) frequently complicates heart failure (HF), and each is associated with lower overall health-related quality of life. We aimed to quantify the incremental burden of AF on the health-related quality of life of patients with HF in clinical practice. METHODS AND RESULTS: We used data from the Utah mEVAL program to analyze patient-reported outcomes (PROs) among patients with HF with and without AF. The primary outcome was the HF-specific Kansas City Cardiomyopathy Questionnaire, with generic PROs as secondary outcomes. Among 1707 patients with HF, 36% had AF (n = 616). Those with HF and AF were older (mean age 69 years vs 58 years, P < .001), more likely to have prior stroke (29% vs 17%, P < .001) and ischemic cardiomyopathy (28% vs 23%, P = .01), but had similar ejection fractions (mean 44% each, P = .6). After adjustment, and compared with HF alone, HF with AF was associated with worse Kansas City Cardiomyopathy Questionnaire scores (adjusted mean difference -3.45, 95% confidence interval [CI] -6.24 to -0.65), and worse Patient-Reported Outcomes Measurement Information System physical function scores (adjusted mean difference -1.63, 95% CI -2.59 to -0.67). The difference in visual analog scale general health was borderline (adjusted mean difference -2.01, 95% CI -4.51 to 0.49), and Patient-Reported Outcomes Measurement Information System depression scores were similar (adjusted mean difference 0.54, 95% CI -0.48 to 1.57). CONCLUSIONS: AF complicates nearly one-third of HF cases, and patients with HF and AF are substantially older and sicker. After adjustment, AF was independently associated with worse disease-specific and overall health-related quality of life than HF alone. Whether maintaining sinus rhythm can improve the HF-related health status of patients with HF in clinical practice should be explored further.

2022 American College of Cardiology/American Heart Association/Heart Failure Society of America Guideline for the Management of Heart Failure: Executive Summary.

BACKGROUND: The 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America (AHA/ACC/HFSA) Guideline for the Management of Heart Failure replaces the 2013 ACCF/AHA Guideline for the Management of Heart Failure and the 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose and manage patients with heart failure. METHODS: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews and other evidence conducted in human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies published through September 2021 were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. RESULTS AND CONCLUSIONS: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments that have high-quality published economic analyses.

The onset of surface-enhanced Raman scattering for single-particle detection of submicroplastics.

Microplastics represent an emerging environmental problem worldwide, raising ecological and food safety concerns. Compared to microplastics, there is growing evidence of an even higher abundance of submicro- and nanoplastics in the environment, but a reliable monitoring method for detecting these smaller-sized plastics is lacking. Herein we presented the application of surface-enhanced Raman scattering (SERS) for this purpose. Particles of polystyrene (PS; 600 nm) were used as the probe analyte. Gold nanourchins (AuNU; 50 nm), i.e. urchin-shaped nanoparticles with irregular spikes around the core, were used as the SERS-active substrate. The effectiveness of SERS on PS was evaluated at a single-particle level with different numbers of AuNU in order to determine the minimum conditions required for the onset of the SERS effect. Our findings suggest that SERS of a single particle of PS can be induced by as few as 1-5 particles of AuNU, and that the use of excitation wavelength at 785 nm is appropriate to meet the red-shifted surface plasmon resonance of AuNU upon aggregation. These specifications provide additional information for the development of SERS-based tools for detecting plastic particles < 1 µm in food and environmental samples.

Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement From the American Heart Association.

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.

The Role of Nonglycolytic Glucose Metabolism in Myocardial Recovery Upon Mechanical Unloading and Circulatory Support in Chronic Heart Failure.

BACKGROUND: Significant improvements in myocardial structure and function have been reported in some patients with advanced heart failure (termed responders [R]) following left ventricular assist device (LVAD)-induced mechanical unloading. This therapeutic strategy may alter myocardial energy metabolism in a manner that reverses the deleterious metabolic adaptations of the failing heart. Specifically, our previous work demonstrated a post-LVAD dissociation of glycolysis and oxidative-phosphorylation characterized by induction of glycolysis without subsequent increase in pyruvate oxidation through the tricarboxylic acid cycle. The underlying mechanisms responsible for this dissociation are not well understood. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose-phosphate pathway and 1-carbon metabolism, which may mediate myocardial recovery in R. METHODS: We prospectively obtained paired left ventricular apical myocardial tissue from nonfailing donor hearts as well as R and nonresponders at LVAD implantation (pre-LVAD) and transplantation (post-LVAD). We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy. RESULTS: Western blot analysis shows significant increase in rate-limiting enzymes of pentose-phosphate pathway and 1-carbon metabolism in post-LVAD R (post-R) as compared with post-LVAD nonresponders (post-NR). The metabolite levels of these enzyme substrates, such as sedoheptulose-6-phosphate (pentose phosphate pathway) and serine and glycine (1-carbon metabolism) were also decreased in Post-R. Furthermore, post-R had significantly higher reduced nicotinamide adenine dinucleotide phosphate levels, reduced reactive oxygen species levels, improved mitochondrial density, and enhanced glycosylation of the extracellular matrix protein, α-dystroglycan, all consistent with enhanced pentose-phosphate pathway and 1-carbon metabolism that correlated with the observed myocardial recovery. CONCLUSIONS: The recovering heart appears to direct glycolytic metabolites into pentose-phosphate pathway and 1-carbon metabolism, which could contribute to cardioprotection by generating reduced nicotinamide adenine dinucleotide phosphate to enhance biosynthesis and by reducing oxidative stress. These findings provide further insights into mechanisms responsible for the beneficial effect of glycolysis induction during the recovery of failing human hearts after mechanical unloading.