A retrospective analysis of anticoagulant safety among heart transplant recipients undergoing endomyocardial biopsy.

BACKGROUND: Transvenous endomyocardial biopsy is an invasive procedure which is used to diagnose rejection following an orthotopic heart transplant. Endomyocardial biopsy is widely regarded as low risk with all-cause complication rates below 5% in most safety studies. Following transplant, some patients require therapeutic anticoagulation. It is unknown whether anticoagulation increases endomyocardial biopsy bleeding risk. METHODS: Records from 2061 endomyocardial biopsies performed for post-transplant rejection surveillance at our institution between November 2016 and August 2022 were reviewed. Bleeding complications were defined as vascular access-related hematoma or bleeding, procedure-related red blood cell transfusion, and new pericardial effusion. Relative risk and small sample-adjusted 95% confidence interval was calculated to investigate the association between bleeding complications and anticoagulation. RESULTS AND CONCLUSIONS: The overall risk of bleeding was 1.2% (25/2061 cases). There was a statistically significant increase in bleeding among patients on intravenous (RR 4.46, CI 1.09-18.32) but not oral anticoagulants (RR .62, CI .15-2.63) compared to patients without anticoagulant exposure. There was a trend toward increased bleeding among patients taking warfarin with INR ≥ 1.8 (RR 3.74, CI .90-15.43). Importantly, no bleeding events occurred in patients taking direct oral anticoagulants such as apixaban. Based on these results, intravenous rather than oral anticoagulation was associated with a significantly higher risk of bleeding complications following endomyocardial biopsy.

Bias in team decision-making for advanced heart failure therapies: model application.

Bias in advanced heart failure therapy allocation results in inequitable outcomes for minoritized populations. The purpose of this study was to examine how bias is introduced during group decision-making with an interprofessional team using Breathett's Model of Heart Failure Decision-Making. This was a secondary qualitative descriptive analysis from a study focused on bias in advanced heart failure therapy allocation. Team meetings were recorded and transcribed from four heart failure centers. Breathett's Model was applied both deductively and inductively to transcripts (n = 12). Bias was identified during discussions about patient characteristics, clinical fragility, and prior clinical decision-making. Some patients were labeled as "good citizens" or as adherent/non-adherent while others benefited from strong advocacy from interprofessional team members. Social determinants of health also impacted therapy allocation. Interprofessional collaboration with advanced heart failure therapy allocation may be enhanced with the inclusion of patient advocates and limit of clinical decision-making using subjective data.

Safety of direct oral anticoagulants in solid organ transplant recipients: A meta-analysis.

There is limited evidence comparing direct oral anticoagulants (DOACs) and warfarin in solid organ transplant (SOT) recipients. We performed a pooled analysis to study the safety and efficacy of DOACs in this patient population. We searched PubMed, Embase, and Scopus databases using the search terms "heart transplant" or "lung transplant" or "liver transplant" or "kidney transplant" or "pancreas transplant" and "direct oral anticoagulant" for literature search. Random effects model with Mantel-Haenszel method was used to pool the outcomes. Pooled analysis included 489 patients, of which 259 patients received DOACs and 230 patients received warfarin. When compared to warfarin, the use of DOACs was associated with decreased risk of composite bleed (RR .49, 95% CI .32-.76, p = .002). There were no differences in rates of major bleeding (RR .55, 95% CI .20-1.49, p = .24) or venous thromboembolism (RR .65, 95% CI .25-1.70, p = .38) between the two groups. Evidence from pooled analysis suggests that DOACs are comparable to warfarin in terms of safety in SOT recipients. Further research is warranted to conclusively determine whether DOACs are safe alternatives to warfarin for anticoagulation in SOT recipients.

The epitranscriptome landscape of small noncoding RNAs in stem cells.

Stem cells (SCs) are unique cells that have an inherent ability to self-renew or differentiate. Both fate decisions are strongly regulated at the molecular level via intricate signaling pathways. The regulation of signaling networks promoting self-renewal or differentiation was thought to be largely governed by the action of transcription factors. However, small noncoding RNAs (ncRNAs), such as vault RNAs, and their post-transcriptional modifications (the epitranscriptome) have emerged as additional regulatory layers with essential roles in SC fate decisions. RNA post-transcriptional modifications often modulate RNA stability, splicing, processing, recognition, and translation. Furthermore, modifications on small ncRNAs allow for dual regulation of RNA activity, at both the level of biogenesis and RNA-mediated actions. RNA post-transcriptional modifications act through structural alterations and specialized RNA-binding proteins (RBPs) called writers, readers, and erasers. It is through SC-context RBPs that the epitranscriptome coordinates specific functional roles. Small ncRNA post-transcriptional modifications are today exploited by different mechanisms to facilitate SC translational studies. One mechanism readily being studied is identifying how SC-specific RBPs of small ncRNAs regulate fate decisions. Another common practice of using the epitranscriptome for regenerative applications is using naturally occurring post-transcriptional modifications on synthetic RNA to generate induced pluripotent SCs. Here, we review exciting insights into how small ncRNA post-transcriptional modifications control SC fate decisions in development and disease. We hope, by illustrating how essential the epitranscriptome and their associated proteome are in SCs, they would be considered as novel tools to propagate SCs for regenerative medicine.

Transcatheter Mitral Valve Repair in Patients with Heart Failure: A Meta-Analysis.

BACKGROUND: Severe secondary mitral regurgitation (MR) is associated with poor prognosis in heart failure patients with left ventricular systolic dysfunction. Few observational and randomized controlled studies demonstrated the efficacy of transcatheter mitral valve repair in heart failure patients with significant MR. A meta-analysis of published studies was performed to evaluate the role of transcatheter mitral valve repair using the MitraClip device in heart failure patients with significant secondary MR. METHODS: A literature search was performed using PubMed, Cochran CENTRAL, and Embase databases using the search terms "percutaneous mitral valve repair" or "transcatheter mitral valve repair" and "heart failure." Studies that compared medical therapy plus transcatheter mitral valve repair using MitraClip to medical therapy alone in heart failure patients with significant secondary MR were included for pooled analysis. A random-effects model with the Mantel-Haenszel method was used to analyze the data. RESULTS: Four studies, 2 randomized controlled and 2 nonrandomized studies met the criteria for analysis. Pooled analysis included a total of 1,421 patients, of which 746 patients underwent transcatheter mitral valve repair and 675 patients received medical therapy alone. When compared to medical therapy, transcatheter mitral valve repair significantly decreased all-cause mortality (OR 0.58, 95% CI 0.37-0.91; p = 0.02). A trend toward significant reduction in rehospitalizations (OR 0.35, 95% CI 0.12-1.00; p = 0.05) was also observed. Periprocedural complications ranged from 7.5 to 12.6%. CONCLUSION: Evidence from pooled analysis suggests that transcatheter mitral valve repair using MitraClip on top of medical therapy, in appropriately selected symptomatic heart failure patients with significant secondary MR, provides survival benefit and may decrease hospitalizations when compared with guideline-directed medical therapy alone.

Electrostatically coupled SiO2 nanoparticles/poly (L-DOPA) antifouling coating on a nanofiltration membrane.

In this work, the fouling resistance of TFC (thin film composite) nanofiltration membranes have been enhanced using an electrostatically coupled SiO2 (silica dioxide) nanoparticles/poly(L-DOPA) (3-(3,4-dihydroxyphenyl)-l-alanine) antifouling coating. SiO2 nanoparticles were synthesized in different size ranges and combined with L-DOPA; and then coated as an anti-fouling layer on the membrane surface by recirculated deposition. Membranes were coated with S-NP (silica nanoparticles) in small (19.8 nm), medium (31.6 nm) and large (110.1 nm) sizes. The zwitterionic compound L-DOPA in the form of self-polymerized poly(L-DOPA) (PDOPA) helped with the attachment of the S-NP to the membrane surface. It was confirmed by AFM (atomic force microscopy) measurement that coating of membranes led to an increase in hydrophilicity and reduction in surface roughness, which in turn led to a 60% reduction in the adhesion force of the foulant on the membrane as compared to the neat membrane. The modified membranes experienced almost no flux decline during the filtration experimental period, whereas the unmodified membrane showed a sharp flux decline. The best coating conditions of silica nanoparticles resulting in enhanced anti-fouling properties were identified. The biofouling film formation on the membranes was evaluated quantitatively using the flow cytometry method. The results indicated that the modified membranes had 50% lower microbial population growth in terms of total event count compared to the neat membrane. Overall, the experimental results have confirmed that the coating of electrostatically coupled SiO2 nanoparticles and PDOPA (S-NP/PDOPA) on TFC-NF (nanofiltration) membrane surfaces is effective in improving the fouling resistance of the membranes. This result has positive implications for reducing membrane fouling in desalination and industrial wastewater treatment applications.

Continuous-Flow Left Ventricular Assist Devices and the Aortic Valve: Interactions, Issues, and Surgical Therapy.

PURPOSE OF REVIEW: Concomitant valve disease is common in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation. In this review, we characterize the epidemiology and management of aortic valve disease following CF-LVAD. RECENT FINDINGS: Studies suggest that 20-40% of patients have mild or greater aortic insufficiency (AI) at baseline and that AI progresses following CF-LVAD implantation. AI, either pre-existing or de novo, can have deleterious effects on LVAD efficacy and clinical outcomes. Surgical methods to correct AI in patients supported with CF-LVAD include central oversewing of the aortic valve, complete closure of the aortic valve, patch closure of the ventriculo-aortic junction, or aortic valve replacement with a bioprosthesis. Transcatheter options have recently emerged as feasible modalities to address AI. CF-LVADs contribute to the progression of aortic insufficiency (AI) and its development de novo. Prompt recognition, assessment, and treatment are important. Aortic valve repairs and replacements, now including TAVR, are the primary surgical methods to correct AI.

Heart Transplantation in Women.

Over the past 5 decades, heart transplantation has become an established therapy with greater quality of life and survival than expected from end-stage heart failure. Nonetheless, challenges still exist, especially for women undergoing heart transplantation. Women have greater post-transplant survival than their male counterparts but worse quality of life. Pregnancy may occur, especially because more women are reaching child-bearing age after transplantation. Successful outcomes have been reported but require a systematic multidisciplinary approach. Women are more likely to be sensitized, with preformed anti-human leukocyte antigens antibodies related to prior pregnancies, posing challenges for their pretransplant and post-transplant management.

Systematic analysis of the role of RNA-binding proteins in the regulation of RNA stability.

mRNA half-lives are transcript-specific and vary over a range of more than 100-fold in eukaryotic cells. mRNA stabilities can be regulated by sequence-specific RNA-binding proteins (RBPs), which bind to regulatory sequence elements and modulate the interaction of the mRNA with the cellular RNA degradation machinery. However, it is unclear if this kind of regulation is sufficient to explain the large range of mRNA stabilities. To address this question, we examined the transcriptome of 74 Schizosaccharomyces pombe strains carrying deletions in non-essential genes encoding predicted RBPs (86% of all such genes). We identified 25 strains that displayed changes in the levels of between 4 and 104 mRNAs. The putative targets of these RBPs formed biologically coherent groups, defining regulons involved in cell separation, ribosome biogenesis, meiotic progression, stress responses and mitochondrial function. Moreover, mRNAs in these groups were enriched in specific sequence motifs in their coding sequences and untranslated regions, suggesting that they are coregulated at the posttranscriptional level. We performed genome-wide RNA stability measurements for several RBP mutants, and confirmed that the altered mRNA levels were caused by changes in their stabilities. Although RBPs regulate the decay rates of multiple regulons, only 16% of all S. pombe mRNAs were affected in any of the 74 deletion strains. This suggests that other players or mechanisms are required to generate the observed range of RNA half-lives of a eukaryotic transcriptome.

Impact of induction immunosuppression on survival in heart transplant recipients: a contemporary analysis of agents.

INTRODUCTION: The impact of induction immunosuppression on long-term survival in heart transplant recipients is unclear. Over the past three decades, practices have varied as induction agents have changed and experiences grew. We sought to evaluate the effect of contemporary induction immunosuppression agents in heart transplant recipients with the primary endpoint of survival, utilizing national registry data. METHODS: We queried the United Network for Organ Sharing (UNOS) data registry for all heart transplants from 1987 to 2012. We restricted our analysis to adult (≥18 yr) recipients performed from 2001-2011 (to allow for the potential for a minimum of 12 months post-transplant follow-up) who received either: no antibody based induction (NONE) or the contemporary agents (INDUCED) of either: basiliximab/daclizumab (IL-2Rab), alemtuzumab, or ATG/ALG/thymoglobulin. Kaplan-Meier estimates of the survival function as well as Cox proportional hazards models were utilized. RESULTS: Of the 17 857 heart transplants that met the inclusion criteria, there were 4635 (26%) reported deaths during the follow-up period. There were 8216 (46%) patients who were INDUCED. Of the INDUCED agents, 55% were IL-2Rab, 4% alemtuzumab, and 40% ALG/ATG/thymoglobulin. Donor and recipient characteristics were evaluated. Overall, being INDUCED did not significantly affect survival in univariable (p = 0.522) and multivariable (p = 0.130) Cox models as well as a propensity score adjusted model (p = 0.733). Among those induced, ATG/ALG/thymoglobulin appeared to have superior survival as compared with IL-2Rab (log-rank p = 0.007, univariable hazard ratio [HR] = 0.886; 95% CI: 0.811-0.968; p = 0.522). However, in a multivariable Cox model that adjusted for recipient age, VAD, BMI, steroid use, CMV match, and ischemic time, the hazard ratio for ALG/ATG/thymoglobulin vs. IL-2Rab was no longer statistically significant (HR = 0.948; 95% CI: 0.850-1.058; p = 0.341). CONCLUSION: In a contemporary analysis of heart transplant recipients, an overall analysis of induction agents does not appear to impact survival, as compared to no induction immunosuppression. While ALG/ATG/thymoglobulin appeared to have a beneficial effect on survival compared to IL-2Rab in the univariable model, this difference was no longer statistically significant once we adjusted for clinically relevant covariates.

The impact of insurance and socioeconomic status on outcomes for patients with left ventricular assist devices.

BACKGROUND: There has been a steady increase of patients living in the community with Left Ventricular Assist Devices (LVADs). There is a significant gap in our fund of knowledge with respect to the impact that insurance and socioeconomic status has on outcomes for LVAD patients. We thus hypothesize that low neighborhood socioeconomic status and receipt of Medicaid, respectively, lead to earlier readmissions, earlier death, as well as longer time to transplantation among LVAD patients. METHODS: This was a retrospective review of 101 patients using existing data in the medical information warehouse database at The Ohio State University Medical Center. Primary outcomes measured included time to first event (first readmission or death), death, and time to rehospitalization. Our secondary outcome of interest included time from LVAD implantation to cardiac transplantation. RESULTS: Recipients of Medicaid did not have an increased risk of adverse events compared with patients without Medicaid coverage. Low Median Household Income (MHI) was associated with an increased risk of readmission (log-rank P = 0.0069) and time to first event (log-rank P = 0.0088). Bridge to transplantation was the only independent predictor of time to death (Hazard Ratio 2.1, [95% confidence interval = 1.03-4.37]). Low MHI and a history of atherosclerosis were both significant predictors for readmission and time to first event. Aldosterone antagonist use decreased the risk of readmission or time to first event by 46%. CONCLUSIONS: LVAD recipients with a low MHI were more likely to be readmitted to the hospital after LVAD implantation. Whether these patients are adequately monitored on an outpatient basis remains unclear.

Functional characterization of Upf1 targets in Schizosaccharomyces pombe.

Nonsense-mediated mRNA decay (NMD) is a highly conserved mechanism of mRNA degradation. NMD eliminates mRNAs containing premature termination codons (PTCs), preventing the production of truncated proteins with possible deleterious effects. However, there is mounting evidence that NMD factors, like Upf1, Upf2 and Upf3, participate in general regulation of gene expression, affecting the expression of genes lacking PTCs. We have used the fission yeast Schizosaccharomyces pombe to identify mRNAs directly regulated by NMD. Using a combination of genetic and biochemical approaches, we have defined a population of fission yeast mRNAs specifically regulated by Upf1. We show that other components of the Upf complex, Upf2 and Upf3, are required for binding of Upf1 to its RNA targets and for the proper response of fission yeast to oxidative stress. Finally, we investigated the physiological importance of this phenomenon, and demonstrate that the Upf1-dependent downregulation of some of its direct targets is necessary for normal resistance to oxidative stress.

Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure.

AIMS: Periodic breathing with central sleep apnoea (CSA) is common in heart failure patients and is associated with poor quality of life and increased risk of morbidity and mortality. We conducted a prospective, non-randomized, acute study to determine the feasibility of using unilateral transvenous phrenic nerve stimulation for the treatment of CSA in heart failure patients. METHODS AND RESULTS: Thirty-one patients from six centres underwent attempted transvenous lead placement. Of these, 16 qualified to undergo two successive nights of polysomnography-one night with and one night without phrenic nerve stimulation. Comparisons were made between the two nights using the following indices: apnoea-hypopnoea index (AHI), central apnoea index (CAI), obstructive apnoea index (OAI), hypopnoea index, arousal index, and 4% oxygen desaturation index (ODI4%). Patients underwent phrenic nerve stimulation from either the right brachiocephalic vein (n = 8) or the left brachiocephalic or pericardiophrenic vein (n = 8). Therapy period was (mean ± SD) 251 ± 71 min. Stimulation resulted in significant improvement in the AHI [median (inter-quartile range); 45 (39-59) vs. 23 (12-27) events/h, P = 0.002], CAI [27 (11-38) vs. 1 (0-5) events/h, P≤ 0.001], arousal index [32 (20-42) vs. 12 (9-27) events/h, P = 0.001], and ODI4% [31 (22-36) vs. 14 (7-20) events/h, P = 0.002]. No significant changes occurred in the OAI or hypopnoea index. Two adverse events occurred (lead thrombus and episode of ventricular tachycardia), though neither was directly related to phrenic nerve stimulation therapy. CONCLUSION: Unilateral transvenous phrenic nerve stimulation significantly reduces episodes of CSA and restores a more natural breathing pattern in patients with heart failure. This approach may represent a novel therapy for CSA and warrants further study.

Impact of Temporary Preoperative Mechanical Support on Heart Transplant Outcomes.

We sought to assess the impact of temporary preoperative mechanical circulatory support (TPMCS) on heart transplantation outcomes. A total of 4,060 adult heart transplants from June 1, 2006, to December 31, 2019, were identified in the Scientific Registry of Transplant Recipients database as having TPMCS. Recipients were divided into groups based on their type of TPMCS: intra-aortic balloon pump (IABP), temporary ventricular assist device (VAD), biventricular assist device (BIVAD), and extracorporeal membrane oxygenation (ECMO). Perioperative outcomes and survival were compared among groups. Recipients with IABP were associated with older age, a smoking history, and a significantly shorter wait list time ( p < 0.01). Recipients with ECMO had a significantly increased in-hospital mortality as well as an increased incidence of dialysis ( p < 0.01). Kaplan-Meier analysis revealed worse 1 and 5 year survival for recipients with ECMO. Cox model demonstrated a significantly increased risk of mortality with BIVAD (hazard ratio [HR], 1.33; 95% CI, 1.12-1.57; p < 0.01) and ECMO (HR, 1.64; 95% CI, 1.33-2.03; p < 0.01). While patients with IABP have a survival comparable to patients without TPMCS or durable left VAD, outcomes for BIVADs and ECMO are not as favorable. Transplantation centers must continue to make careful choices about the type of TPMCS utilized before heart transplant.

Allocation changes in heart transplantation: What has really changed?

OBJECTIVE: In 2018, the heart allocation system changed status classifications and broadened geographic distribution. We examined this change at a national level based on the immediate pre- and postchange periods. METHODS: Using the Scientific Registry of Transplant Recipients database, we identified all adult primary, isolated heart transplants from October 18, 2017, to October 17, 2019. Two time periods were compared: (1) October 18, 2017, to October 17, 2018 (pre); and (2) October 18, 2018, to October 17, 2019 (post). Comparisons were made between groups, and a multivariable logistic regression model was created to identify factors associated with pretransplant temporary mechanical circulatory support. Volume analysis at the regional, state, and center level was also conducted as the primary focus. RESULTS: A total of 5381 independent heart transplants were identified within the time frame. On unadjusted analysis, there was a significant increase in temporary mechanical circulatory support (pre, 11.1%; post, 36.2%, P < .01) and decrease in waitlist days (pre, 93 days; post, 41 days; P < .01). Distance traveled (nautical miles) (pre, 83; post, 225; P < .01) and ischemic time (hours) (pre, 3.0; post, 3.4; P < .01) were significantly increased. On multivariable analysis, the postallocation time period was independently associated with temporary MCS (odds ratio, 4.463; 95% confidence interval, 3.844-5.183; P < .001). Transplant volumes did not significantly change after the allocation change at a regional, state, and center level. CONCLUSIONS: Since the planned alteration to the allocation system, there have been changes in the use of temporary mechanical circulatory support as well as distance and ischemic time associated with transplant, but no significant volume changes were observed. Continued observation of outcomes and volume under the new allocation system will be necessary in the upcoming years.

Group Dynamics and Allocation of Advanced Heart Failure Therapies-Heart Transplants and Ventricular Assist Devices-By Gender, Racial, and Ethnic Group.

Background US regulatory framework for advanced heart failure therapies (AHFT), ventricular assist devices, and heart transplants, delegate eligibility decisions to multidisciplinary groups at the center level. The subjective nature of decision-making is at risk for racial, ethnic, and gender bias. We sought to determine how group dynamics impact allocation decision-making by patient gender, racial, and ethnic group. Methods and Results We performed a mixed-methods study among 4 AHFT centers. For ≈ 1 month, AHFT meetings were audio recorded. Meeting transcripts were evaluated for group function scores using de Groot Critically Reflective Diagnoses protocol (metrics: challenging groupthink, critical opinion sharing, openness to mistakes, asking/giving feedback, and experimentation; scoring: 1 to 4 [high to low quality]). The relationship between summed group function scores and AHFT allocation was assessed via hierarchical logistic regression with patients nested within meetings nested within centers, and interaction effects of group function score with gender and race, adjusting for patient age and comorbidities. Among 87 patients (24% women, 66% White race) evaluated for AHFT, 57% of women, 38% of men, 44% of White race, and 40% of patients of color were allocated to AHFT. The interaction between group function score and allocation by patient gender was statistically significant (P=0.035); as group function scores improved, the probability of AHFT allocation increased for women and decreased for men, a pattern that was similar irrespective of racial and ethnic groups. Conclusions Women evaluated for AHFT were more likely to receive AHFT when group decision-making processes were of higher quality. Further investigation is needed to promote routine high-quality group decision-making and reduce known disparities in AHFT allocation.

A novel approach for assessing bias during team-based clinical decision-making.

Many clinical processes include multidisciplinary group decision-making, yet few methods exist to evaluate the presence of implicit bias during this collective process. Implicit bias negatively impacts the equitable delivery of evidence-based interventions and ultimately patient outcomes. Since implicit bias can be difficult to assess, novel approaches are required to detect and analyze this elusive phenomenon. In this paper, we describe how the de Groot Critically Reflective Diagnoses Protocol (DCRDP) can be used as a data analysis tool to evaluate group dynamics as an essential foundation for exploring how interactions can bias collective clinical decision-making. The DCRDP includes 6 distinct criteria: challenging groupthink, critical opinion sharing, research utilization, openness to mistakes, asking and giving feedback, and experimentation. Based on the strength and frequency of codes in the form of exemplar quotes, each criterion was given a numerical score of 1-4 with 1 representing teams that are interactive, reflective, higher functioning, and more equitable. When applied as a coding scheme to transcripts of recorded decision-making meetings, the DCRDP was revealed as a practical tool for examining group decision-making bias. It can be adapted to a variety of clinical, educational, and other professional settings as an impetus for recognizing the presence of team-based bias, engaging in reflexivity, informing the design and testing of implementation strategies, and monitoring long-term outcomes to promote more equitable decision-making processes in healthcare.

Percutaneous left ventricular partitioning in patients with chronic heart failure and a prior anterior myocardial infarction: Results of the PercutAneous Ventricular RestorAtion in Chronic Heart failUre PaTiEnts Trial.

OBJECTIVES: The aim of this study was to assess the feasibility, safety, and preliminary efficacy of a novel percutaneous left ventricular partitioning device (VPD) in patients with chronic heart failure (HF) and a prior anterior myocardial infarction. BACKGROUND: Anterior myocardial infarction is frequently followed by left ventricular remodeling, HF, and increased long-term morbidity and mortality. METHODS: Thirty-nine patients were enrolled in a multinational, nonrandomized, longitudinal investigation. The primary end point was an assessment of safety, defined as the successful delivery and deployment of the VPD and absence of device-related major adverse cardiac events over 6 months. Secondary (exploratory) efficacy end points included changes in hemodynamics and functional status and were assessed serially throughout the study. RESULTS: Ventricular partitioning device placement was not attempted in 5 (13%) of 39 subjects. The device was safely and successfully implanted in 31 (91%) of the remaining 34 patients or 79% of all enrolled patients. The 6-month rate of device-related major adverse cardiac event occurred in 5 (13%) of 39 enrolled subjects and 5 (15%) of 34 treated subjects, with 1 additional event occurring between 6 and 12 months. For patients discharged with the device to 12 months (n = 28), New York Heart Association class (2.5 ± 0.6 to 1.3 ± 0.6, P < .001) and quality-of-life scores (38.6 ± 6.1 to 28.4 ± 4.4, P < .002) improved significantly; however, the 6-minute hall walk distance (358.5 ± 20.4 m to 374.7 ± 25.6 m, P nonsignificant) only trended toward improvement. CONCLUSIONS: The left VPD appears to be relatively safe and potentially effective in the treatment for patients with HF and a prior anterior myocardial infarction. However, these limited results suggest the need for further evaluation in a larger randomized controlled trial.

Telemonitoring in chronic heart failure.

Clinical management of refractory heart failure remains challenging, with a high rate of rehospitalizations despite advances in medical and device therapy. Care can be provided in person, via telehomecare (by telephone), or telemonitoring, which involves wireless technology for remote follow-up. Telemonitoring wirelessly transmits parameters such as weight, heart rate, or blood pressure for review by health-care professionals. Cardiac implantable devices (defibrillators and cardiac resynchronization therapy) also transmit continually interrogated physiological data, such as heart rate variability or intrathoracic impedance, which may be of value to predict patients at greater risk of hospitalization for heart failure. The use of remote monitoring techniques facilitates a rapid and regular review of such data by health-care workers as part of a heart failure management programme. Current evidence supports the feasibility of such an approach but routinely assessed parameters have been shown not to impact patient outcomes. Devices that directly assess cardiac haemodynamic status through invasive measurement of pressures are currently under investigation and could potentially increase the sensitivity and specificity of predicting heart failure events. The current evidence for telemonitoring and remote monitoring, including implantable haemodynamic devices, will be reviewed.

Interfacing Machine Learning and Microbial Omics: A Promising Means to Address Environmental Challenges.

Microbial communities are ubiquitous and carry an exceptionally broad metabolic capability. Upon environmental perturbation, microbes are also amongst the first natural responsive elements with perturbation-specific cues and markers. These communities are thereby uniquely positioned to inform on the status of environmental conditions. The advent of microbial omics has led to an unprecedented volume of complex microbiological data sets. Importantly, these data sets are rich in biological information with potential for predictive environmental classification and forecasting. However, the patterns in this information are often hidden amongst the inherent complexity of the data. There has been a continued rise in the development and adoption of machine learning (ML) and deep learning architectures for solving research challenges of this sort. Indeed, the interface between molecular microbial ecology and artificial intelligence (AI) appears to show considerable potential for significantly advancing environmental monitoring and management practices through their application. Here, we provide a primer for ML, highlight the notion of retaining biological sample information for supervised ML, discuss workflow considerations, and review the state of the art of the exciting, yet nascent, interdisciplinary field of ML-driven microbial ecology. Current limitations in this sphere of research are also addressed to frame a forward-looking perspective toward the realization of what we anticipate will become a pivotal toolkit for addressing environmental monitoring and management challenges in the years ahead.