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We describe a case of an orthotopic heart transplant recipient who presented with chest pain related to blunt chest trauma 3 weeks post-transplantation. Electrocardiogram showed anterior ST-segment elevation. Coronary angiography revealed a dissection of the mid-distal left anterior descending artery with preserved antegrade flow. Conservative management of the coronary artery dissection was pursued. While the patient had a favorable long-term clinical outcome, the coronary dissection persisted on 1- and 2-year follow-up coronary angiography., Competing Interests: Declaration of competing interest We assure that:, (Copyright © 2022 Elsevier Inc. All rights reserved.)

From bacterial quorum sensing to human language, communication is essential for social interactions. Nematodes produce and sense pheromones to communicate among individuals and respond to environmental changes. These signals are encoded by different types and mixtures of ascarosides, whose modular structures further enhance the diversity of this nematode pheromone language. Interspecific and intraspecific differences in this ascaroside pheromone language have been described previously, but the genetic basis and molecular mechanisms underlying the variation remain largely unknown. Here, we analyzed natural variation in the production of 44 ascarosides across 95 wild Caenorhabditis elegans strains using high-performance liquid chromatography coupled to high-resolution mass spectrometry. We discovered wild strains defective in the production of specific subsets of ascarosides ( e.g. , the aggregation pheromone icas#9) or short- and medium-chain ascarosides, as well as inversely correlated patterns between the production of two major classes of ascarosides. We investigated genetic variants that are significantly associated with the natural differences in the composition of the pheromone bouquet, including rare genetic variants in key enzymes participating in ascaroside biosynthesis, such as the peroxisomal 3-ketoacyl-CoA thiolase, daf-22 , and the carboxylesterase cest-3 . Genome-wide association mappings revealed genomic loci harboring common variants that affect ascaroside profiles. Our study yields a valuable dataset for investigating the genetic mechanisms underlying the evolution of chemical communication.

Background: Gastrointestinal bleeding (GIB) is one of the most common bleeding complications associated with left ventricular assist devices (LVAD). Currently, there is no strong evidence or clear guidance for which secondary GIB prophylaxis strategy should be implemented after the discontinuation of aspirin., Methods: Our single-center study describes the outcomes of 26 LVAD patients who experienced a total of 49 GIB events: these individuals were either in Group-1 (lower INR target range) or Group-2 (lower INR target plus a hemostatic agent) as the secondary prophylaxis strategy. Each GIB event was considered an independent event. Outcomes assessed were bleeding reoccurrence rates, time to next GIB, acute GIB strategies, GIB-free days, thromboembolic events, survival, coagulation, and hematologic parameters., Results: GIB reoccurrence rates were not statistically different: Group-1, 9 (40.9%), versus Group-2, 15 (55.6%); p = 0.308. Danazol was utilized 81.5% of the time as the designated hemostatic agent. Additionally, no significant differences were observed with all of our secondary outcome measures for bleeding, ischemic events, or survival., Conclusion: While our study was not powered to assess the clinical outcomes related to survival and thromboembolic events, no discernable increased risk for ischemic events including pump thrombosis were observed. Our data suggest that a lower INR target range plus danazol does not confer any additional benefit over a lower INR target range only approach. The results of this report are hypothesis-generating and additional studies are warranted to elucidate the optimal antithrombotic strategy and role of hemostatic agents in reducing the risk of recurrent GIB events., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Individuals can exhibit differences in metabolism that are caused by the interplay of genetic background, nutritional input, microbiota and other environmental factors 1-4 . It is difficult to connect differences in metabolism to genomic variation and derive underlying molecular mechanisms in humans, owing to differences in diet and lifestyle, among others. Here we use the nematode Caenorhabditis elegans as a model to study inter-individual variation in metabolism. By comparing three wild strains and the commonly used N2 laboratory strain, we find differences in the abundances of both known metabolites and those that have not to our knowledge been previously described. The latter metabolites include conjugates between 3-hydroxypropionate (3HP) and several amino acids (3HP-AAs), which are much higher in abundance in one of the wild strains. 3HP is an intermediate in the propionate shunt pathway, which is activated when flux through the canonical, vitamin-B 12 -dependent propionate breakdown pathway is perturbed 5 . We show that increased accumulation of 3HP-AAs is caused by genetic variation in HPHD-1, for which 3HP is a substrate. Our results suggest that the production of 3HP-AAs represents a 'shunt-within-a-shunt' pathway to accommodate a reduction-of-function allele in hphd-1. This study provides a step towards the development of metabolic network models that capture individual-specific differences of metabolism and more closely represent the diversity that is found in entire species., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Hemodynamic values from right heart catheterization aid diagnosis and clinical decision-making but may not predict outcomes. Mixed venous oxygen saturation percentage and pulmonary capillary wedge pressure relate to cardiac output and congestion, respectively. We theorized that a novel, simple ratio of these measurements could estimate cardiovascular prognosis., Methods: We queried Veterans Affairs' databases for clinical, hemodynamic, and outcome data. Using the index right heart catheterization between 2010 and 2016, we calculated the ratio of mixed venous oxygen saturation-to-pulmonary capillary wedge pressure, termed ratio of saturation-to-wedge (RSW). The primary outcome was time to all-cause mortality; secondary outcome was 1-year urgent heart failure presentation. Patients were stratified into quartiles of RSW, Fick cardiac index (CI), thermodilution CI, and pulmonary capillary wedge pressure alone. Kaplan-Meier curves and Cox proportional hazards models related comparators with outcomes., Results: Of 12 019 patients meeting inclusion criteria, 9826 had values to calculate RSW (median 4.00, interquartile range, 2.67-6.05). Kaplan-Meier curves showed early, sustained separation by RSW strata. Cox modeling estimated that increasing RSW by 50% decreases mortality hazard by 19% (estimated hazard ratio, 0.81 [95% CI, 0.79-0.83], P <0.001) and secondary outcome hazard by 28% (hazard ratio, 0.72 [95% CI, 0.70-0.74], P <0.001). Among the 3793 patients with data for all comparators, Cox models showed RSW best associated with outcomes (by both C statistics and Bayes factors). Furthermore, pulmonary capillary wedge pressure was superior to thermodilution CI and Fick CI. Multivariable adjustment attenuated without eliminating the association of RSW with outcomes., Conclusions: In a large national database, RSW was superior to conventional right heart catheterization indices at assessing risk of mortality and urgent heart failure presentation. This simple calculation with routine data may contribute to clinical decision-making in this population.

Purpose of Review: Progression of heart failure (HF) and its unpredictable and volatile nature, often requires advanced therapies including heart transplant. Mechanical circulatory support plays an integral part in the advanced treatment options. This technology can be deployed in several ways, particularly in the preparation and patient optimization for heart transplants. This article discusses the use of temporary and durable devices and their deployment strategies in the pre and posttransplant period., Recent Findings: Recently temporary mechanical support devices have allowed us to improve survival to transplant as well as posttransplant. Early implementation of temporary devices both for stabilization of advanced HF patients being considered for transplant as well as those with posttransplant primary graft dysfunction (although utilization of extracorporeal membrane oxygenation has repeatedly shown to be associated with worse outcomes compared to the other devices discussed), is reflective of the degree of disease progression in these patients. The outcomes of patients supported with durable devices have significantly improved with advancing technology. HeartMate 3 device has not only been shown to improve survival as well as the quality of life but in comparison to its predecessor, has been shown to decrease the morbidity associated with this technology., Summary: Both temporary and durable devices are now associated with improved survival and allow us to transplant patients in a more stable and safer manner with fewer adverse events. Based on the new United Network of Organ Sharing allocation system, it allows us to upgrade those who do not have the luxury of time to wait for a transplant. Primary graft dysfunction now also can be assisted with those devices, which is reflected in improved survival of posttransplant patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) has resulted in many challenges in patient care, especially among high-risk populations such as heart transplant recipients. Patients with heart transplant experience a significantly higher mortality rate with COVID-19 infection, and management is based on extrapolation from clinical trials done on nontransplant patients and from clinical experience. Here we report 4 cases of patients with heart transplant who presented with COVID-19 infection in late 2020. Patients presented with symptoms similar to those seen in the general population. All 4 patients were admitted to the hospital, and they were all treated with dexamethasone. In addition, 2 patients received remdesivir. Immunosuppressive medications were adjusted to maintain adequate levels of immunosuppression but at the same time allow for an adequate immune response against the infection. All patients were discharged alive from the hospital. We then performed a literature review on studies that included heart transplant patients who developed the infection and developed suggestions for a standardized management approach, which we share in this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To our knowledge, no cases of Bartonella henselae endocarditis leading to subsequent heart transplantation salvage therapy have been published. We present a case of a 29-year-old man with cat-inflicted B henselae endocarditis and concurrent worsening heart failure, who then underwent successful heart transplantation 50 days following diagnosis. Treatment and monitoring strategies used in this patient are discussed. Furthermore, we review literature related to heart transplantation salvage therapy for endocarditis due to other intracellular pathogens., (© 2019 Wiley Periodicals, Inc.)

Purpose of Review: Pulmonary arterial hypertension (PAH) leads to progressive increases in pulmonary vascular resistance (PVR), right heart failure, and death if left untreated. This review will summarize and discuss recent updates in the classification and management of patients with PAH., Recent Findings: PAH requires careful hemodynamic assessment and is defined by a mean pulmonary artery pressure > 20 mmHg with normal left-sided filling pressures and a PVR ≥ 3 Wood units. Most patients with PAH require targeted pharmacotherapy based on multiparametric risk stratification. Significant improvements in clinical outcome have been realized through the approval of 14 unique pharmacotherapeutic options. The latest clinical recommendations provide the updated hemodynamic definition and clinical classification as well as evidence-based treatment recommendations. An important change is the focus on initial upfront combination therapy for most patients with PAH. Structured follow-up and escalation of treatment for those not achieving low-risk status is paramount.

Heart failure is a progressive condition that continues to increase in both incidence and prevalence despite pharmacologic treatment. The high rate of morbidity and mortality associated with advanced heart failure has led to exploration of additional treatments, which include surgical interventions to improve outcomes. Heart transplant remains the gold standard but, because of the persistent donor shortage and increasing number of patients with advanced heart failure, mechanical circulatory support is gaining acceptance and can be used as a bridge to heart transplant for those eligible or as destination therapy., (Published by Elsevier Inc.)

Background: Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established., Methods: MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control., Results: Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; P < 0.001), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, P = 0.14 and OR 1.23; CI: 0.96-1.58, P = 0.101, respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, P = 0.0048 and 4.88: 95% CI 0.756 to 9.0133, P = 0.0204, respectively)., Conclusions: Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients.

Spontaneous retrobulbar hemorrhage is a rare phenomenon observed after surgery not directly involving the orbit. When it occurs, presentation is usually obvious, and it carries high morbidity unless emergent and timely surgical treatment is instituted. There are only a handful of cases associated with cardiac surgery, and to our knowledge no cases with heart transplantation. We present a case of a 35-year-old woman who underwent orthotopic heart transplantation for peripartum cardiomyopathy and developed spontaneous retrobulbar hemorrhage., (Published by Elsevier Inc.)