Outcome of Patients With Systolic Heart Failure Who Underwent Sympathectomy for Ventricular Arrhythmia.

Cardiac sympathetic denervation (CSD) is a surgical procedure increasingly used for managing ventricular arrhythmia refractory to conventional medical therapy. Long-term outcomes of CSD in patients with systolic heart failure has not been well studied. This observational study aimed to evaluate the medical co-morbidities and outcomes of patients with systolic heart failure who underwent CSD performed as treatment for ventricular arrhythmia refractory to conventional therapy. A retrospective analysis in adult patients with ventricular arrhythmia and systolic heart failure who underwent unilateral or bilateral CSD at a single center was performed. Unadjusted Kaplan-Meier survival curves were constructed to evaluate survival after CSD. Between June 1, 2011 and March 31, 2021, 32 adult patients (age 62 ± 11.6 years, 88% male, left ventricular ejection fraction 22% ± 8.2%) with systolic heart failure underwent unilateral left (n = 4), unilateral right (n = 1), or bilateral CSD (n = 27). Mean survival after CSD was 613 ± 745 days, and the mean time from CSD to death was 291 ± 447 days. The cumulative probability of survival 1 year after CSD was 61.4%. In this single-center observational study, CSD performed for refractory ventricular arrhythmia showed favorable survival in patients with systolic heart failure. In conclusion, this study lays the groundwork for a more in-depth analysis of the potential survival benefits of CSD in this patient group.

The Rhodium Analogue of Coenzyme B12 as an Anti-Photoregulatory Ligand Inhibiting Bacterial CarH Photoreceptors.

Coenzyme B12 (AdoCbl; 5'-deoxy-5'-adenosylcobalamin), the quintessential biological organometallic radical catalyst, has a formerly unanticipated, yet extensive, role in photoregulation in bacteria. The light-responsive cobalt-corrin AdoCbl performs this nonenzymatic role by facilitating the assembly of CarH photoreceptors into DNA-binding tetramers in the dark, suppressing gene expression. Conversely, exposure to light triggers the decomposition of this AdoCbl-bound complex by a still elusive photochemical mechanism, activating gene expression. Here, we have examined AdoRhbl, the non-natural rhodium analogue of AdoCbl, as a photostable isostructural surrogate for AdoCbl. We show that AdoRhbl closely emulates AdoCbl in its uptake by bacterial cells and structural functionality as a regulatory ligand for CarH tetramerization, DNA binding, and repressor activity. Remarkably, we find AdoRhbl is photostable even when bound "base-off/His-on" to CarH in vitro and in vivo. Thus, AdoRhbl, an antivitamin B12, also represents an unprecedented anti-photoregulatory ligand, opening a pathway to precisely target biomimetic inhibition of AdoCbl-based photoregulation, with new possibilities for selective antibacterial applications. Computational biomolecular analysis of AdoRhbl binding to CarH yields detailed structural insights into this complex, which suggest that the adenosyl group of photoexcited AdoCbl bound to CarH may specifically undergo a concerted non-radical syn-1,2-elimination mechanism, an aspect not previously considered for this photoreceptor.

A new opportunity for patient selection and optimization: Systematic review of cognitive frailty in patients undergoing left ventricular assist device implantation.

The prognostic implication of cognitive frailty assessment in patients undergoing left ventricular assist device (LVAD) implantation remains unclear. We conducted a systematic review to evaluate assessment strategies and their significance for patients undergoing LVAD implantation. A comprehensive search of PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature from inception until September 2022 and a review of meeting proceedings were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that investigated the prognostic value of cognitive frailty or any related cognition-based assessment in patients undergoing LVAD implantation were included. Study characteristics, patient demographics, and type of cognitive assessment were extracted. Primary outcomes included length of stay, readmissions, and all-cause mortality. Of 664 records retrieved, 12 (4 prospective, 8 retrospective) involving 16 737 subjects (mean age, 56.9 years; 78.3% men) met inclusion criteria; 67% of studies used the Montreal Cognitive Assessment to assess cognitive frailty. Outcomes reported were highly variable, with 42% reporting readmission, 33% reporting LOS, and 83% reporting mortality data; only two studies provided data on all three. Cognitive frailty was associated with prolonged length of stay in 75% of studies reporting this outcome. Only 40% and 60% of studies that reported readmissions and mortality outcomes, respectively, suggested a predictive association. Pre-LVAD cognitive frailty is likely associated with worse outcomes postimplant. However, the heterogenous reporting of outcomes data and lack of consistent definitions in the literature limit its prognostic value. Additional research on markers for cognitive frailty and improved standards of reporting may allow for future analyses and enhance preoperative risk assessment and patient care. Geriatr Gerontol Int 2024; 24: 204-210.

Left Ventricular Assist Device Use in Minorities: An Analysis of the National Inpatient Sample.

Minorities are less likely to receive a left ventricular assist device (LVAD). This, however, is based on total implant data. By examining rates of LVAD implant among patients admitted with heart failure complicated by cardiogenic shock, we sought to further elucidate LVAD utilization rates and racial disparities. Utilizing the National Inpatient Sample from 2013 to 2019, all patients admitted with a primary diagnosis of heart failure complicated by cardiogenic shock were included for analysis. Those who then received an LVAD during that hospitalization defined the LVAD utilization which was examined for any racial disparities. Left ventricular assist device utilization was low across all racial groups with no significant difference noted in univariate analysis. Non-Hispanic Blacks had the highest length of stay (LOS), the highest proportion of discharge to home (71.52%), and the lowest inpatient mortality (6.33%). Multivariable modeling confirmed the relationship between race and LOS; however, no differences were noted in mortality. Non-Hispanic Blacks were found to be less likely to receive an LVAD; however, when controlling for payer, median household income, and comorbidities, this relationship was no longer seen. Left ventricular assist devices remain an underutilized therapy in cardiogenic shock. When using a multivariable model, race does not appear to affect LVAD utilization.

Reconsidering FDA Guidelines: A Single-Center Experience of Prolonged Impella 5.5 Support.

OBJECTIVE: Impella 5.5 (Abiomed, Danvers, MA, USA) is approved by the US Food and Drug Administration (FDA) for mechanical circulatory support for ≤14 days. It is unknown whether prolonged support is associated with worse outcomes. We sought to review our single-center experience with Impella 5.5 and compare outcomes based on support duration. METHODS: We retrospectively reviewed adult patients (≥18 years old) supported with Impella 5.5 at our institution (May 2020 to April 2023). Patients on prolonged support (>14 days) were compared with those supported for ≤14 days. RESULTS: There were 31 patients supported with Impella 5.5 including 14 (45.2%) supported >14 days. Median support duration for those on prolonged support was 43.5 (interquartile range [IQR] 25 to 63.5) days versus 8 (IQR 6, 13) days for those who were not (P < 0.001). Overall, the device-related complication rate was 9.7% and did not differ between groups (P = 0.08). Overall, 30-day postimplant survival was 71% and did not differ by support duration (P = 0.2). In-hospital mortality was 32% and did not differ between cohorts (P > 0.99). Among those surviving to explant (n = 22), long-term strategy included bridge to durable ventricular assist device (18%, n = 4), cardiac transplant (55%, n = 12), and cardiac recovery (27%, n = 6). CONCLUSIONS: High-risk patients with cardiogenic shock may be supported with Impella 5.5 beyond the FDA-approved duration without increased risk of complications or mortality.

Transthyretin Cardiac Amyloidosis Disguised as Light Chain Amyloidosis or Multiple Myeloma?

We describe 2 challenging cases of cardiac transthyretin amyloidosis initially treated as cardiac amyloidosis light chain in the setting of active myeloma. Endomyocardial biopsy with mass spectrometry was essential to confirm the appropriate diagnosis to direct the treatment.

Recurrent Cardiac Sarcoidosis and Giant Cell Myocarditis After Heart Transplant: A Case Report and Systematic Literature Review.

Recurrence of cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) after heart transplant is rare, with rates of 5% in CS and 8% in GCM. We aim to identify all reported cases of recurrence in the literature and to assess clinical course, treatments, and outcomes to improve understanding of the conditions. A systematic review, utilizing Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, was conducted by searching MEDLINE/PubMed and Embase of all available literature describing post-transplant recurrent granulomatous myocarditis, CS, or GCM. Data on demographics, transplant, recurrence, management, and outcomes data were collected from each publication. Comparison between the 2 groups were made using standard statistical approaches. Post-transplant GM recurrence was identified in 39 patients in 33 total publications. Reported cases included 24 GCM, 12 CS, and 3 suspected cases. Case reports were the most frequent form of publication. Mean age of patients experiencing recurrence was 42 years for GCM and 48 years for CS and favored males (62%). Time to recurrence ranged from 2 weeks to 9 years post-transplant, occurring earlier in GCM (mean 1.8 vs 3.0 years). Endomyocardial biopsies (89%) were the most utilized diagnostic method over cardiac magnetic resonance and positron emission tomography. Recurrence treatment regimens involved only steroids in 40% of CS, whereas other immunomodulatory regimens were utilized in 70% of GCM. In conclusion, GCM and CS recurrence after cardiac transplantation holds associated risks including concurrent acute cellular rejection, a higher therapeutic demand for GCM recurrence compared with CS, and mortality. New noninvasive screening techniques may help modify post-transplant monitoring regimens to increase both early detection and treatment of recurrence.

Learning and assessment strategies to develop specific and transversal competencies for a humanized medical education.

Introduction: Medical education should promote the development of skills and abilities that can be applied to real-world work performance. The aim of this study is to evaluate technical and methodological knowledge, as well as physician-patient communication skills, as one of the most important transversal competencies that a good physician should acquire; all this in a reliable, accurate and objective way. Methods: We present a rubric specifically designed and implemented for the evaluation of specific and transversal competencies in the physiology practical sessions, during the second year of the medical degree. The assessment consists in two evaluation tests: 1) a theoretical test that consists of multiple-choice questions. Students must demonstrate that they have acquired adequate theoretical knowledge (specific competency "to know"); 2) a practical test, in which students are evaluated by the rubric through the simulation of a medical consultation. Thus, demonstrating their ability to execute/apply what they have learned in class (specific competency "to know how to do"). They are also evaluated on the transversal competencies that we call "communication with the patient" (transversal competency "to know how to be there") and "dealing with the patient" (transversal competency "to know how to be"). Results: We evaluated whether there were differences in the grades obtained by students when the transversal competencies were not assessed (academic years 2017-2018 and 2018-2019; n = 289), and when the transversal competencies were assessed by applying the rubric in the academic years 2019-2020, 2021-2022, and 2022-2023 (n = 526). Furthermore, we present a student perception that supports the use of clinical simulation and our rubric as a good method within the competency learning process. Discussion: The acquisition of these competencies, starting from the first courses of undergraduate education, helps to raise the students' awareness in the development of a more humanized medicine, allowing a better response to the patients' needs. Our rubric, which clearly indicate the performance criteria, have become an excellent method to carry out the assessment of competencies, both for students and teachers, since they allow to obtain clear evidence of the level of acquisition and application of knowledge.

Utilization of the percutaneous left ventricular support as bridge to heart transplantation across the United States: In-depth UNOS database analysis.

BACKGROUND: Intra-aortic balloon pump (IABP) and Impella device utilization as a bridge to heart transplantation (HTx) have risen exponentially. We aimed to explore the influence of device selection on HTx outcomes, considering regional practice variation. METHODS: A retrospective longitudinal study was performed on a United Network for Organ Sharing (UNOS) registry dataset. We included adult patients listed for HTx between October 2018 and April 2022 as status 2, as justified by requiring IABP or Impella support. The primary end-point was successful bridging to HTx as status 2. RESULTS: Of 32,806 HTx during the study period, 4178 met inclusion criteria (Impella n = 650, IABP n = 3528). Waitlist mortality increased from a nadir of 16 (in 2019) to a peak of 36 (in 2022) per thousand status 2 listed patients. Impella annual use increased from 8% in 2019 to 19% in 2021. Compared to IABP, Impella patients demonstrated higher medical acuity and lower success rate of transplantation as status 2 (92.1% vs 88.9%, p < 0.001). The IABP:Impella utilization ratio varied widely between regions, ranging from 1.77 to 21.31, with high Impella use in Southern and Western states. However, this difference was not justified by medical acuity, regional transplant volume, or waitlist time and did not correlate with waitlist mortality. CONCLUSIONS: The shift in utilizing Impella as opposed to IABP did not improve waitlist outcomes. Our results suggest that clinical practice patterns beyond mere device selection determine successful bridging to HTx. There is a critical need for objective evidence to guide tMCS utilization and a paradigm shift in the UNOS allocation system to achieve equitable HTx practice across the United States.

Harmful Algae Impacting Aquatic Organisms: Recent Field and Laboratory Observations.

Algal blooms formed by some phytoplankton species can produce toxins or alter environmental conditions that can affect aquatic organisms and water quality, with impacts on the aquaculture and fisheries industries that can pose a risk to public health [...].

Pharmacological Therapy Optimization for Heart Failure: A Practical Guide for the Internist.

Heart failure carries significant morbidity and mortality and affects a large population of patients cared for predominantly by primary care physicians. The complexity of managing heart failure patients is increasing as new therapies continue to emerge. This review outlines important clinical pearls and proposes strategies for optimization of medical therapy.

Amyloid transthyretin cardiac amyloidosis with different manifestations, test findings and types.

Amyloid transthyretin amyloidosis usually presents with cardiac amyloidosis manifestations, most commonly with a heart failure syndrome. The history and physical examination offer clues of other cardiac and extracardiac manifestations. Taking a detailed history is essential in elucidating pertinent family and medical history that may increase suspicion for amyloidosis. Further, certain findings on electrocardiogram and imaging should raise suspicion and trigger further workup that can confirm the diagnosis, since treatment is evolving.

Prognostic Value of Frailty for Heart Failure Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review.

Frailty is associated with poor clinical outcomes in heart failure patients. The impact of frailty on outcomes following left ventricular assist device (LVAD) implantation, however, is less clearly defined. We therefore sought to conduct a systematic review to evaluate current frailty assessment strategies and their significance for patients undergoing LVAD implantation. We conducted a comprehensive electronic search of PubMed, Embase, and CINAHL databases from inception until April 2021 for studies examining frailty in patients undergoing LVAD implantation. Study characteristics, patient demographics, type of frailty measurement, and outcomes were extracted. Outcomes were organized into 5 basic categories: implant length of stay (iLOS), 1-year mortality, rehospitalization, adverse events, and quality of life (QOL). Of the 260 records retrieved, 23 studies involving 4935 patients satisfied the inclusion criteria. Approaches to measuring frailty varied, with the 2 most common being sarcopenia determined by computed tomography and Fried's frailty phenotype assessment. Outcomes of interest were also widely variable, with iLOS stay and mortality being the most frequently reported, albeit with differing definitions of both between studies. The heterogeneity among included studies precluded quantitative synthesis. Narrative synthesis showed that frailty by any measure is more likely to be associated with higher mortality, longer iLOS, more adverse events and worse QOL post-LVAD implant. Frailty can be a valuable prognostic indicator in patients undergoing LVAD implantation. Further studies are needed to determine the most sensitive frailty assessment, as well as the ways in which frailty may serve as a modifiable target to improve outcomes following LVAD implantation.

Artificial intelligence guidance of advanced heart failure therapies: A systematic scoping review.

Introduction: Artificial intelligence can recognize complex patterns in large datasets. It is a promising technology to advance heart failure practice, as many decisions rely on expert opinions in the absence of high-quality data-driven evidence. Methods: We searched Embase, Web of Science, and PubMed databases for articles containing "artificial intelligence," "machine learning," or "deep learning" and any of the phrases "heart transplantation," "ventricular assist device," or "cardiogenic shock" from inception until August 2022. We only included original research addressing post heart transplantation (HTx) or mechanical circulatory support (MCS) clinical care. Review and data extraction were performed in accordance with PRISMA-Scr guidelines. Results: Of 584 unique publications detected, 31 met the inclusion criteria. The majority focused on outcome prediction post HTx (n = 13) and post durable MCS (n = 7), as well as post HTx and MCS management (n = 7, n = 3, respectively). One study addressed temporary mechanical circulatory support. Most studies advocated for rapid integration of AI into clinical practice, acknowledging potential improvements in management guidance and reliability of outcomes prediction. There was a notable paucity of external data validation and integration of multiple data modalities. Conclusion: Our review showed mounting innovation in AI application in management of MCS and HTx, with the largest evidence showing improved mortality outcome prediction.

DIAPH1 mediates progression of atherosclerosis and regulates hepatic lipid metabolism in mice.

Atherosclerosis evolves through dysregulated lipid metabolism interwoven with exaggerated inflammation. Previous work implicating the receptor for advanced glycation end products (RAGE) in atherosclerosis prompted us to explore if Diaphanous 1 (DIAPH1), which binds to the RAGE cytoplasmic domain and is important for RAGE signaling, contributes to these processes. We intercrossed atherosclerosis-prone Ldlr-/- mice with mice devoid of Diaph1 and fed them Western diet for 16 weeks. Compared to male Ldlr-/- mice, male Ldlr-/- Diaph1-/- mice displayed significantly less atherosclerosis, in parallel with lower plasma concentrations of cholesterol and triglycerides. Female Ldlr-/- Diaph1-/- mice displayed significantly less atherosclerosis compared to Ldlr-/- mice and demonstrated lower plasma concentrations of cholesterol, but not plasma triglycerides. Deletion of Diaph1 attenuated expression of genes regulating hepatic lipid metabolism, Acaca, Acacb, Gpat2, Lpin1, Lpin2 and Fasn, without effect on mRNA expression of upstream transcription factors Srebf1, Srebf2 or Mxlipl in male mice. We traced DIAPH1-dependent mechanisms to nuclear translocation of SREBP1 in a manner independent of carbohydrate- or insulin-regulated cues but, at least in part, through the actin cytoskeleton. This work unveils new regulators of atherosclerosis and lipid metabolism through DIAPH1.

Thrombotic and Hemorrhagic Complications Following Left Ventricular Assist Device Placement: An Emphasis on Gastrointestinal Bleeding, Stroke, and Pump Thrombosis.

The left ventricular assist device (LVAD) is a mechanical circulatory support device that supports the heart failure patient as a bridge to transplant (BTT) or as a destination therapy for those who have other medical comorbidities or complications that disqualify them from meeting transplant criteria. In patients with severe heart failure, LVAD use has extended survival and improved signs and symptoms of cardiac congestion and low cardiac output, such as dyspnea, fatigue, and exercise intolerance. However, these devices are associated with specific hematologic and thrombotic complications. In this manuscript, we review the common hematologic complications of LVADs.

Proton Transfers to DNA in Native Electrospray Ionization Mass Spectrometry: A Quantum Mechanics/Molecular Mechanics Study.

Native electrospray ionization-ion mobility mass spectrometry (N-ESI/IM-MS) is a powerful approach for low-resolution structural studies of DNAs in the free state and in complex with ligands. Solvent vaporization is coupled with proton transfers from ammonium ions to the DNA, resulting in a reduction of the DNA charge. Here we provide insight into these processes by classical molecular dynamics and quantum mechanics/molecular mechanics free energy calculations on the d(GpCpGpApApGpC) heptamer, for which a wealth of experiments is available. Our multiscale simulations, consistent with experimental data, reveal a highly complex scenario. The proton either sits on one of the molecules or is fully delocalized on both, depending on the level of hydration of the analytes and the size of the droplets formed during the electrospray experiments. This work complements our previous study of the intramolecular proton transfer on the same heptamer occurring after the processes studied here, and together, they provide a first molecular view of proton transfer in N-ESI/IM-MS.

A glutamine-based single α-helix scaffold to target globular proteins.

The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-helices. These interactions offer opportunities for therapeutic intervention but their modulation with small molecules is challenging because they bury large surfaces. Linear peptides that display the residues that are key for binding can be targeted to globular proteins when they form stable helices, which in most cases requires their chemical modification. Here we present rules to design peptides that fold into single α-helices by instead concatenating glutamine side chain to main chain hydrogen bonds recently discovered in polyglutamine helices. The resulting peptides are uncharged, contain only natural amino acids, and their sequences can be optimized to interact with specific targets. Our results provide design rules to obtain single α-helices for a wide range of applications in protein engineering and drug design.

Role of miR-199a-5p in the post-transcriptional regulation of ABCA1 in response to hypoxia in peritoneal macrophages.

Hypoxia is a crucial factor contributing to maintenance of atherosclerotic lesions. The ability of ABCA1 to stimulate the efflux of cholesterol from cells in the periphery, particularly foam cells in atherosclerotic plaques, is an important anti-atherosclerotic mechanism. The posttranscriptional regulation by miRNAs represents a key regulatory mechanism of a number of signaling pathways involved in atherosclerosis. Previously, miR-199a-5p has been shown to be implicated in the endocytic and retrograde intracellular transport. Although the regulation of miR-199a-5p and ABCA1 by hypoxia has been already reported independently, the role of miR-199a-5p in macrophages and its possible role in atherogenic processes such us regulation of lipid homeostasis through ABCA1 has not been yet investigated. Here, we demonstrate that both ABCA1 and miR-199a-5p show an inverse regulation by hypoxia and Ac-LDL in primary macrophages. Moreover, we demonstrated that miR-199a-5p regulates ABCA1 mRNA and protein levels by directly binding to its 3'UTR. As a result, manipulation of cellular miR-199a-5p levels alters ABCA1 expression and cholesterol efflux in primary mouse macrophages. Taken together, these results indicate that the correlation between ABCA1-miR-199a-5p could be exploited to control macrophage cholesterol efflux during the onset of atherosclerosis, where cholesterol alterations and hypoxia play a pathogenic role.