RESUMO
BACKGROUND: Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown. METHODS: To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders. RESULTS: These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions. CONCLUSIONS: This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Transcriptoma , Estudos Prospectivos , Fosfopeptídeos/metabolismo , Proteômica , Doadores de Tecidos , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismoRESUMO
Left ventricular assist devices (LVADs) are an established treatment modality for advanced heart failure (HF). It has been shown that through volume and pressure unloading they can lead to significant functional and structural cardiac improvement, allowing LVAD support withdrawal in a subset of patients. In the first part of this review, we discuss the historical background, current evidence on the incidence and assessment of LVAD-mediated cardiac recovery, and out-comes including quality of life after LVAD support withdrawal. In the second part, we discuss current and future opportunities to promote LVAD-mediated reverse remodeling and improve our pathophysiological understanding of HF and recovery for the benefit of the greater HF population.
RESUMO
We examined how convenience and financial incentives influence patient willingness to dispose of leftover prescription opioids after surgery. We also identified additional barriers and facilitators to disposal. Background: In the United States, up to 70% of surgical patients are prescribed opioids and up to 92% will have leftover tablets. Most do not dispose of leftover opioids, increasing the risk for opioid-related harm. Current interventions promoting opioid disposal have shown mixed success. Methods: We conducted a mixed methods study using a standard gamble survey and semi-structured interviews. Participants estimated willingness to dispose in 16 scenarios with varying convenience (time requirements of <5, 15, 30, and 60 minutes) and financial incentives ($0, $5, $25, $50). We estimated the likelihood of disposal using a multivariable mixed effects modified Poisson regression model. Semi-structured interviews explored how convenience, financial incentives, and other barriers and facilitators influenced decisions to dispose. Results: Fifty-five participants were surveyed and 42 were interviewed. Most were willing to dispose when the time required was <15 minutes. Few were willing to dispose if the process required 60 minutes, although a $50 financial incentive increased rates from 9% to 36%. Anxiety about future pain, opioid scarcity, recreational use, family safety, moral beliefs, addiction, theft, and environmental harm also influenced decision-making. Conclusions: Interventions promoting opioid disposal should focus on convenience, but the selective use of financial incentives can be effective. Tailoring interventions to individual barriers and facilitators could also increase disposal rates.
RESUMO
This diagnostic/prognostic study evaluates the 2 × 24-hour predischarge opioid consumption guideline for opioid prescribing.