RNA m6 A modification enzymes shape innate responses to DNA by regulating interferon ß.

Modification of mRNA by N6-adenosine methylation (m6A) on internal bases influences gene expression in eukaryotes. How the dynamic genome-wide landscape of m6A-modified mRNAs impacts virus infection and host immune responses remains poorly understood. Here, we show that type I interferon (IFN) production triggered by dsDNA or human cytomegalovirus (HCMV) is controlled by the cellular m6A methyltrasferase subunit METTL14 and ALKBH5 demethylase. While METTL14 depletion reduced virus reproduction and stimulated dsDNA- or HCMV-induced IFNB1 mRNA accumulation, ALKBH5 depletion had the opposite effect. Depleting METTL14 increased both nascent IFNB1 mRNA production and stability in response to dsDNA. In contrast, ALKBH5 depletion reduced nascent IFNB1 mRNA production without detectably influencing IFN1B mRNA decay. Genome-wide transcriptome profiling following ALKBH5 depletion identified differentially expressed genes regulating antiviral immune responses, while METTL14 depletion altered pathways impacting metabolic reprogramming, stress responses, and aging. Finally, we determined that IFNB1 mRNA was m6A-modified within both the coding sequence and the 3' untranslated region (UTR). This establishes that the host m6A modification machinery controls IFNß production triggered by HCMV or dsDNA. Moreover, it demonstrates that responses to nonmicrobial dsDNA in uninfected cells, which shape host immunity and contribute to autoimmune disease, are regulated by enzymes controlling m6A epitranscriptomic changes.

Call to action for drug interactions between tirzepatide and heart failure guideline-directed medical therapy.

BACKGROUND: No drug interaction between the guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) and glucose-dependent insulinotropic polypeptide (GIP)-glucagon-like peptide-1 (GLP-1) agonists is currently indexed in available drug interaction databases or package inserts for tirzepatide, the first dual GIP/GLP-1 agonist. The objective of our case series is to present 3 patients with HF who required modification in GDMT regimens for HFrEF or loop diuretic therapy after tirzepatide initiation. CASE SUMMARY: Three patients older than 60 years with HFrEF receiving GDMT agents (angiotensin receptor neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors) were initiated on tirzepatide for weight loss management. After initiating tirzepatide therapy, all 3 patients developed symptomatic hypotension. Two cases had acute kidney injury owing to tirzepatide's direct vasodilation, natriuresis, reduction in extracellular volume, and weight loss. GDMT regimens and diuretic therapy were significantly modified to improve these adverse reactions. PRACTICE IMPLICATIONS: Clinicians must closely monitor vital signs and volume status after initiating tirzepatide for potential need to modify GDMT regimens. Authors request a call to action to index the drug interaction between GDMT agents and tirzepatide in major drug interaction databases for a potential hypotension or dehydration risk.

Quantitative single photon emission computed tomography derived standardized uptake values on 99mTc-PYP scan in patients with suspected ATTR cardiac amyloidosis.

Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR.

Age stratified sex-related differences in incidence, management, and outcomes of cardiogenic shock.

BACKGROUND: There is a lack of data on age-stratified sex differences in the incidence, treatment, and outcomes of cardiogenic shock (CS). We sought to study these differences from a contemporary database. METHODS: Patients admitted with CS (2004-2018) were identified from the United States National Inpatient Sample. We compared CS (acute myocardial infarction-related cardiogenic shock [AMI-CS] and non-acute myocardial infarction-related cardiogenic shock [Non-AMI-CS]) incidence, management, and outcomes in males and females, stratified into four age groups (20-44, 45-64, 65-84, and ≥85 years of age). Propensity score matching (PSM) was used for adjustment. RESULTS: A total of 1,506,281 weighted hospitalizations for CS were included (AMI-CS, 39%; Non-AMI-CS, 61%). Across all age groups, females had a lower incidence of CS compared with males. After PSM and among the AMI-CS cohort, higher mortality among females compared with males was observed in the age groups 45-64 (28.5% vs. 26.3%) and 65-84 years (39.3% vs. 37.9%) (p < 0.01, for all). Among the Non-AMI-CS cohort, higher mortality among females compared with males was observed in the age groups 20-44 (33.5% vs. 30.5%), 45-64 (35.1% vs. 31.9%), and 65-84 years (41.7% vs. 40.3%) (p < 0.01, for all). Similar age-dependent differences in the management of CS were also observed between females and males. CONCLUSIONS: Females have a lower incidence of CS regardless of age. Significant disparities in the management and outcomes of CS were observed based on sex. However, these disparities varied by age and etiology of CS (AMI-CS vs. Non-AMI-CS) with pronounced disparity among females in the age range of 45-84 years.

Repression of eEF2K transcription by NF-κB tunes translation elongation to inflammation and dsDNA-sensing.

Gene expression is rapidly remodeled by infection and inflammation in part via transcription factor NF-κB activation and regulated protein synthesis. While protein synthesis is largely controlled by mRNA translation initiation, whether cellular translation elongation factors are responsive to inflammation and infection remains poorly understood. Here, we reveal a surprising mechanism whereby NF-κB restricts phosphorylation of the critical translation elongation factor eEF2, which catalyzes the protein synthesis translocation step. Upon exposure to NF-κB-activating stimuli, including TNFα, human cytomegalovirus infection, or double-stranded DNA, eEF2 phosphorylation on Thr56, which slows elongation to limit protein synthesis, and the overall abundance of eEF2 kinase (eEF2K) are reduced. Significantly, this reflected a p65 NF-κB subunit-dependent reduction in eEF2K pre-mRNA, indicating that NF-κB activation represses eEF2K transcription to decrease eEF2K protein levels. Finally, we demonstrate that reducing eEF2K abundance regulates protein synthesis in response to a bacterial toxin that inactivates eEF2. This establishes that NF-κB activation by diverse physiological effectors controls eEF2 activity via a transcriptional repression mechanism that reduces eEF2K polypeptide abundance to preclude eEF2 phosphorylation, thereby stimulating translation elongation and protein synthesis. Moreover, it illustrates how nuclear transcription regulation shapes translation elongation factor activity and exposes how eEF2 is integrated into innate immune response networks orchestrated by NF-κB.

Evaluating Sacubitril/Valsartan Dose Dependence on Clinical Outcomes in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Limited evidence is available regarding low (24/26 mg) and middle (49/51 mg) doses of sacubitril/valsartan. OBJECTIVES: The purpose of this study was to investigate the effect of sacubitril/valsartan dose on heart failure (HF) hospitalization and mortality in patients with HF with reduced ejection fraction (HFrEF). METHODS: A retrospective multicenter cohort study compared 3 doses of sacubitril/valsartan in patients with HFrEF. The coprimary outcomes were all-cause mortality and rehospitalization for HF. Propensity matching analysis was performed. RESULTS: Of 721 eligible patients, propensity matching created a cohort with an effective sample size of 652 (24/26-mg group [n = 326], 49/51-mg group [n = 147], 97/103-mg group [n = 179]). The HF hospitalization rates were 29.14% in the 24/26-mg group, 19.51% in the 49/51-mg group, and 16.10% in the 97/103-mg group (24/26 vs 49/51 mg: HR = 1.56, 95% CI = 1.04-2.34; 24/26 vs 97/103 mg: HR = 1.79, 95% CI = 1.18-2.73; 49/51 vs 97/103 mg: HR = 1.15, 95% CI = 0.70-1.89). All-cause mortality rates were 29.63% in the 24/26-mg group, 17.58% in the 49/51-mg group, and 9.27% in the 97/103-mg group (24/26 vs 49/51 mg: HR = 1.67, 95% CI = 1.07-2.59; 24/26 vs 97/103 mg: HR = 2.56, 95% CI = 1.54-4.24; 49/51 vs 97/103 mg: HR = 1.54, 95% CI = 0.84-2.82). CONCLUSION AND RELEVANCE: Sacubitril/valsartan 97/103- or 49/51-mg dose is associated with a lower mortality or hospitalization rate for HF in patients receiving sacubitril/valsartan compared with the 24/26-mg dose group.

Microtubule Inhibitors and Cardiotoxicity.

PURPOSE OF REVIEW: Cancer and heart disease are the leading causes of mortality in the USA. Advances in cancer therapies, namely, the development and use of chemotherapeutic agents alone or in combination, are becoming increasingly prevalent. RECENT FINDINGS: Many chemotherapeutic agents have been associated with adverse cardiovascular manifestations. The mechanisms of these sequelae remain incompletely understood. In particular, microtubule inhibitor (MTI) agents have been related to the development of heart failure, myocardial ischemia, and conduction abnormalities. At present, there are no guidelines for patients undergoing MTI therapy as it pertains to both preventative and mitigatory strategies for cardiovascular complications. We conducted a literature review focusing on content related to the use of MTIs and their effect on the cardiovascular system. MTIs have been associated with various forms of cardiotoxicity, and fatal cardiotoxicities are rare. The most well-described cardiotoxicities are brady- and tachyarrhythmias. The co-administration of anthracycline-based agents with MTIs can increase the risk of cardiotoxicity.

Induced Hypothermia in Patients with Cardiac Arrest and a Non-shockable Rhythm: Meta-analysis and Trial Sequential Analysis.

BACKGROUND: Controversy surrounds utilization of induced hypothermia (IHT) in comatose cardiac arrest (CA) survivors with a non-shockable rhythm. METHODS: We conducted a meta-analysis and trial sequential analysis (TSA) comparing IHT with no IHT approaches in patients with CA and a non-shockable rhythm. The primary outcome of interest was favorable neurological outcomes (FNO) defined using the Cerebral Performance Category (CPC) score of 1 or 2. Secondary endpoints were survival at discharge and survival beyond 90 days. RESULTS: A total of 9 studies with 10,386 patients were included. There was no difference between both groups in terms of FNO (13% vs. 13%, RR 1.34, 95% CI 0.96-1.89, p = 0.09, I2 = 88%), survival at discharge (20% vs. 22%, RR 1.09, 95% CI 0.88-1.36, p = 0.42, I2 = 76%), or survival beyond 90 days (16% vs. 15%, RR 0.92, 95% CI 0.61-1.40, p = 0.69, I2 = 83%). The TSA showed firm evidence supporting the lack of benefit of IHT in terms of survival at discharge. However, the Z-curves failed to cross the conventional and TSA (futility) boundaries for FNO and survival beyond 90 days, indicating lack of sufficient evidence to draw firm conclusions regarding these outcomes. CONCLUSION: In this meta-analysis of 9 studies, the utilization of IHT was not associated with a survival benefit at discharge. Although the meta-analysis showed lack of benefit of IHT in terms of FNO and survivals beyond 90 days, the corresponding TSA showed high probability of type-II statistical error, and therefore more randomized controlled trials powered for these outcomes are needed.

Cardiac mechanics in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical entity associated with significant morbidity and mortality. Common comorbidities including hypertension, coronary artery disease, diabetes, chronic kidney disease, obesity, and increasing age predispose to preclinical diastolic dysfunction that often progresses to frank HFpEF. Clinical HFpEF is typically associated with some degree of diastolic dysfunction, but can occur in the absence of many conventional diastolic dysfunction indices. The exact biologic links between risk factors, structural changes, and clinical manifestations are not clearly apparent. Innovative approaches including deformation imaging have enabled deeper understanding of HFpEF cardiac mechanics beyond conventional metrics. Furthermore, predictive analytics through data-driven platforms have allowed for a deeper understanding of HFpEF phenotypes. This review focuses on the changes in cardiac mechanics that occur through preclinical myocardial dysfunction to clinically apparent HFpEF.

Interaction of Quinone-Related Electron Acceptors with Hydropersulfide Na2S2: Evidence for One-Electron Reduction Reaction.

We previously reported that 9,10-phenanthraquinone (9,10-PQ), an atmospheric electron acceptor, undergoes redox cycling with dithiols as electron donors, resulting in the formation of semiquinone radicals and monothiyl radicals; however, monothiols have little reactivity. Because persulfide and polysulfide species are highly reducing, we speculate that 9,10-PQ might undergo one-electron reduction with these reactive sulfides. In the present study, we explored the redox cycling capability of a variety of quinone-related electron acceptors, including 9,10-PQ, during interactions with the hydropersulfide Na2S2 and its related polysulfides. No reaction occurred when 9,10-PQ was incubated with Na2S; however, when 5 µM 9,10-PQ was incubated with either 250 µM Na2S2 or Na2S4, we detected extensive consumption of dissolved oxygen (84 µM). Under these conditions, both the semiquinone radicals of 9,10-PQ and their thiyl radical species were also detected using ESR, suggesting that a redox cycle reaction occurred utilizing one-electron reduction processes. Notably, the perthiyl radicals remained stable even under aerobic conditions. Similar phenomenon has also been observed with other electron acceptors, such as pyrroloquinoline quinone, vitamin K3, and coenzyme Q10. Our experiments with N-methoxycarbonyl penicillamine persulfide (MCPSSH), a precursor for endogenous cysteine persulfide, suggested the possibility of a redox coupling reaction with 9,10-PQ inside cells. Our study indicates that hydropersulfide and its related polysulfides are efficient electron donors that interact with quinones. Redox coupling reactions between quinoid electron acceptors and such highly reactive thiols might occur in biological systems.

Restriction of Human Cytomegalovirus Replication by ISG15, a Host Effector Regulated by cGAS-STING Double-Stranded-DNA Sensing.

Accumulation of the interferon-stimulated gene 15 (ISG15) protein product, which is reversibly conjugated to numerous polypeptide targets, impacts the proteome and physiology of uninfected and infected cells. While many viruses, including human cytomegalovirus (HCMV), blunt host antiviral defenses by limiting ISG expression, the overall abundance of ISG15 monomer and protein conjugates rises in HCMV-infected cells. However, the molecular signals underlying ISG15 accumulation and whether the ISG15 polypeptide itself influences HCMV infection biology remain unknown. Here, we establish that the ISG15 gene product itself directly regulates HCMV replication and that its accumulation restricts productive virus growth. Although ISG15 monomer and protein conjugate accumulation was induced in cells infected with UV-inactivated HCMV, it was subsequently reduced, but not eliminated, by an immediate-early (IE) or early (E) virus-encoded function(s). Instead, HCMV-induced ISG15 monomer and protein conjugate accumulation was dependent upon the double-stranded DNA (dsDNA) sensor cyclic GMP-AMP synthase (cGAS), the innate immune adaptor STING, and interferon signaling. Significantly, dsDNA itself was sufficient to induce cGAS-, STING-, and interferon signaling-dependent ISG15 monomer and conjugate protein accumulation in uninfected cells. Accumulation of ISGylated proteins in uninfected cells treated with dsDNA was prevented by expressing the HCMV multifunctional IE1 transactivator. This demonstrates that expression of a single host interferon-stimulated gene, ISG15, restricts HCMV replication, and that IE1 is sufficient to blunt ISGylation in response to dsDNA sensing in uninfected cells. Moreover, it establishes that ISGylation modifies the proteomes of virus-infected and uninfected normal cells in response to cell-intrinsic dsDNA sensing dependent upon cGAS-STING.IMPORTANCE By antagonizing type I interferon production and action, many viruses, including human cytomegalovirus (HCMV), evade host defenses. However, levels of the interferon-induced ISG15 protein, which is covalently conjugated to host and viral proteins, increase in HCMV-infected cells. How ISG15 accumulation is regulated and whether the ISG15 polypeptide influences HCMV replication remain unknown. This study establishes that ISG15 itself restricts HCMV replication and that HCMV-induced ISG15 accumulation is triggered by host defenses that detect cytoplasmic double-stranded DNA (dsDNA). Remarkably, dsDNA triggered ISG15 accumulation even in uninfected cells, and this was reduced by HCMV IE1 expression. This shows that ISG15 itself controls the replication of HCMV, which causes life-threatening disease among the immunocompromised and is a significant source of congenital morbidity and mortality among newborns. Moreover, it demonstrates that ISG15 modifies the uninfected cell proteome in response to dsDNA, potentially impacting responses to DNA vaccines, gene therapy, and autoimmune disease pathogenesis.

Heart Transplantation in Giant Cell Myocarditis: Analysis of the United Network for Organ Sharing Registry.

BACKGROUND: Giant cell myocarditis (GCM) is a lethal, rapidly progressive disease, for which heart transplantation is the treatment of choice. We sought to describe the characteristics and outcomes of patients with GCM who undergo heart transplantation. METHODS AND RESULTS: We used the United Network for Organ Sharing thoracic organ transplantation registry to identify adults with GCM as the primary diagnosis and compared their characteristics and outcomes with patients who underwent transplantation for other types of myocarditis and for idiopathic dilated cardiomyopathy (IDCMP). A total of 32 patients with GCM were compared with 219 patients with myocarditis and 14,221 patients with IDCMP. Median age at listing for GCM was 52 years (interquartile range 40-55 y), and the majority were white (94%), male (63%), and listed as 1A (44%). Biventricular assist devices were used more frequently in GCM compared with IDCMP (31% vs 2%; P < .001). After transplantation, there were no statistically significant differences among GCM, myocarditis, and IDCMP patients regarding pacemaker implantation, dialysis initiation, or stroke rate. GCM patients had increased risk of acute rejection compared with IDCMP patients (16% vs 5.0%; P = .021) but no difference in rehospitalization for rejection among the 3 etiologies (P = .88). The cumulative survivals for GCM patients at 1, 5, and 10 years were 94%, 82%, and 68%, respectively, which was similar to the other etiologies (P = .11). CONCLUSIONS: Compared with patients with IDCMP, those with GCM present more acutely and have significantly higher utilization of biventricular mechanical circulatory support. Despite higher rates of early rejection, post-transplantation survival of patients with GCM was similar to that of other myocarditides and IDCMP.

The chemical biology of HNO signaling.

Nitroxyl (HNO) is a simple molecule with significant potential as a pharmacological agent. For example, its use in the possible treatment of heart failure has received recent attention due to its unique therapeutic properties. Recent progress has been made on the elucidation of the mechanisms associated with its biological signaling. Importantly, the biochemical mechanisms described for HNO bioactivity are consistent with its unique and novel chemical properties/reactivity. To date, much of the biology of HNO can be associated with interactions and modification of important regulatory thiol proteins. Herein will be provided a description of HNO chemistry and how this chemistry translates to some of its reported biological effects.

Advanced Heart Failure Therapies for Cancer Therapeutics-Related Cardiac Dysfunction.

End-stage heart failure in cancer survivors may result from cardiotoxic chemotherapy and/or chest radiation and require advanced therapies, including left ventricular assist devices (LVADs) and transplantation. Traditionally, such therapies have been underutilized in cancer survivors owing to lack of experience and perceived risk of cancer recurrence. Recent data from large registries, however, have shown excellent outcomes of LVADs and transplantation in cancer survivors, albeit subject to careful selection and special considerations. This article summarizes all aspects of advanced heart failure therapies in patients with cancer therapy-related cardiac dysfunction and underscores the need for careful selection of these candidates.

The chemical biology of hydropersulfides (RSSH): Chemical stability, reactivity and redox roles.

Recent reports indicate the ubiquitous prevalence of hydropersulfides (RSSH) in mammalian systems. The biological utility of these and related species is currently a matter of significant speculation. The function, lifetime and fate of hydropersulfides will be assuredly based on their chemical properties and reactivity. Thus, to serve as the basis for further mechanistic studies regarding hydropersulfide biology, some of the basic chemical properties/reactivity of hydropersulfides was studied. The nucleophilicity, electrophilicity and redox properties of hydropersulfides were examined under biological conditions. These studies indicate that hydropersulfides can be nucleophilic or electrophilic, depending on the pH (i.e. the protonation state) and can act as good one- and two-electron reductants. These diverse chemical properties in a single species make hydropersulfides chemically distinct from other, well-known sulfur containing biological species, giving them unique and potentially important biological function.

Effect of Cocaine, Amphetamine, and Cannabis Use Disorders on 30-day Readmissions of Patients with Heart Failure.

There is limited evidence demonstrating whether cannabis, cocaine, amphetamine, or other stimulants use contributes to heart failure (HF) readmissions. We used the National Readmissions Database years 2016-2018 to identify patients with HF with and without substance use disorder (SUD) (defined as a composite of cannabis, cocaine, or other stimulant use disorders). The main outcome was to assess the risk of 30-day readmissions in HF patients with and without SUD. Of 978,217 HF hospitalizations that met the inclusion criteria, 34,717 (3.5%) had concomitant SUD. HF patients with SUD had significantly higher hazard for 30-day all-cause readmissions (adjusted hazard ratio [aHR] 1.16 [1.12-1.21]; P < 0.01) compared to HF patients without SUD. In conclusion, HF patients with SUD have an elevated risk of 30-day all-cause readmissions, mainly driven by cocaine and other stimulant disorders. Screening for substance use in hospitalized HF patients as well as timely referral for treatment are important to prevent HF readmissions.

Sacubitril/Valsartan Does Not Change the Use and Dose of Loop Diuretics in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: There is no standard approach for managing the use or dose of loop diuretics after initiating sacubitril/valsartan. OBJECTIVE: To investigate longitudinal trends in loop diuretic therapy use and doses during the initial 6 months following sacubitril/valsartan initiation. METHODS: This retrospective cohort study included adult patients who were initiated on sacubitril/valsartan in cardiology clinics. Inclusion criteria were patients diagnosed with heart failure with reduced ejection fraction (ejection fraction ≤40%) and initiated on sacubitril/valsartan in an outpatient setting. We investigated longitudinal trends in the prevalence of loop diuretic use and furosemide equivalent dose at baseline, 2 weeks, 1 month, 3 month and 6 months following sacubitril/valsartan initiation. RESULTS: A total of 427 patients were included in the final cohort. Compared to the baseline loop diuretic use and dose, there were no significant longitudinal changes in the prevalence of loop diuretic use or the furosemide equivalent dose over the 6 months following sacubitril/valsartan initiation. The use of sacubitril/valsartan was not significantly associated with reductions in the use or dose of loop diuretics over a 6-month follow-up period. CONCLUSION: The use of sacubitril/valsartan did not significantly change the use or dose of loop diuretics over 6-month follow-up period. Initiation of sacubitril/valsartan may not need a pre-emptive loop diuretic dose reduction.

Evaluation of a pharmacist-provider collaborative clinic for treatment of iron deficiency in patients with heart failure.

PURPOSE: Intravenous iron therapy is recommended to improve symptoms and exercise tolerance in patients with heart failure (HF) with -reduced ejection fraction and iron deficiency (ID), but there are limited published data on the implementation of intravenous iron therapy in practice. A pharmacist-provider collaborative ID treatment clinic was established within an advanced HF and pulmonary hypertension service to optimize IV iron therapy. The objective was to evaluate the clinical impacts of the pharmacist-provider collaborative ID treatment clinic. METHODS: A retrospective cohort study was performed to compare clinical outcomes among patients of the collaborative ID treatment clinic (the postimplementation group) and a cohort of patients who received usual care (the preimplementation group). The study included patients 18 years of age or older with diagnosed HF or pulmonary hypertension who met prespecified criteria for ID. The primary outcome was adherence to institutional intravenous iron therapy guidance. A key secondary outcome was ID treatment goal achievement. RESULTS: A total of 42 patients in the preimplementation group and 81 in the postimplementation group were included in the study. The rate of adherence to the institutional guidance was significantly improved in the postimplementation group (93%) compared to the preimplementation group (40%). There was no significant difference in the ID therapeutic target achievement rate between the pre- and postimplementation groups (38% vs 48%). CONCLUSION: Implementing a pharmacist-provider collaborative ID treatment clinic significantly increased the number of patients who adhered to intravenous iron therapy guidance compared to usual care.

Sex-based outcomes of surgical myectomy for hypertrophic cardiomyopathy: An analysis from the National Readmission Database.

BACKGROUND: There is a paucity of data on sex differences in outcomes after surgical myectomy (SM) for hypertrophic cardiomyopathy (HCM). METHODS: Patients who received SM for HCM during October 1, 2015, through December 31, 2018, were identified from the US National Readmission Database. The primary end point of this study was in-hospital mortality. The secondary end points were major bleeding, acute kidney injury, new pacemaker implantation, severe disability surrogates (non-home discharge and need for mechanical ventilation), resources utilization surrogates (length of stay and cost of hospitalization), and 30-day outcomes (readmission rate, mortality, and new pacemaker insertion). RESULTS: A total of 3031 patients were included in the current analysis. Using propensity score matching, 2 well matched cohorts were compared (women = 1170 and men = 1127). Women had a higher requirement for new pacemaker insertion compared with men (10.9% vs 6.8%; P = .029), higher number of non-home discharges (13.8% vs 7.9%; P < .01), and longer length of hospital stay (median = 7 [interquartile range, 5-9] days) versus (median = 6 [interquartile range, 5-8] days). There was no difference in in-hospital mortality, major bleeding, blood transfusion, acute kidney injury, or hospitalization costs for women versus men. At 30 days, women continued to show a higher need for pacemaker insertion (11.3% vs 7.1%; P = .03) and had a higher readmission rate than men (10.9% vs 7.1%; P = .02). There was no difference in 30-day mortality between women and men (3% vs 2.4%; P = .54). CONCLUSIONS: Among the HCM cohort who received SM, significant sex-based differences in the outcomes were observed. Women had higher new pacemaker insertion rate, higher non-home discharge rate, and higher rate of 30-day readmission compared with men.