Recovery of left ventricular function is associated with improved outcomes in LVAD recipients.

BACKGROUND: The significance of recovered left ventricular ejection fraction (LVEF) in LVAD recipients, outside of pump explantation, is unclear. METHODS: Patients undergoing first LVAD implantation at Duke University Hospital between 2006 and 2017 were evaluated for LVEF recovery up to 2 years following implant. Occurrence of gastrointestinal bleeding (GIB), hospitalization for heart failure (HF), pump thrombosis and death were assessed before and after LVEF recovery. RESULTS: Of 286 patients who met inclusion criteria, 9.8% reached a "threshold" of recovery with an LVEF ≥ 40%. 17.4% achieved "relative" recovery with an increase in LVEF ≥ 10% since LVAD implantation. For either definition, recovered patients had a lower incidence of a composite endpoint of GIB, HF hospitalization, pump thrombosis, or death compared to patients without recovery. Patients with "threshold" recovery had 4.7 events per 100 patient-years (95% CI, 0.7-33.6) compared to 48.8 events per 100 patient-years (95% CI, 39.5-60.3) without "threshold" recovery [p = .020]. Those with "relative" recovery had 14.1 events per 100 patient-years [95% CI, 5.9-33.8] versus 50.7 events per 100 patient-years (95% CI, 40.7-63.0) without "relative" recovery [p = 0.005]. However, improved outcomes in the "relative" recovery group were limited to those who also met the "threshold" definition. Importantly, among patients who achieved "threshold" recovery, the incidence of the composite endpoint declines in the postrecovery period, suggesting that LVEF recovery mechanistically results in improved outcomes. CONCLUSIONS: An LVEF ≥ 40% associates with better outcomes in LVAD recipients. Methods to promote recovery could reduce morbidity and mortality related to LVAD support.

In-Hospital Therapy for Heart Failure With Reduced Ejection Fraction in the United States.

OBJECTIVES: This study sought to characterize in-hospital treatment patterns and associated patient outcomes among patients hospitalized for heart failure (HF) in U.S. clinical practice. BACKGROUND: Hospitalizations for HF are common and associated with poor patient outcomes. Real-world patterns of in-hospital treatment, including diuretic therapy, in contemporary U.S. practice are unknown. METHODS: Using Optum de-identified Electronic Health Record data from 2007 through 2018, patients hospitalized for a primary diagnosis of HF (ejection fraction ≤40%) and who were hemodynamically stable at admission, without concurrent acute coronary syndrome or end-stage renal disease, and treated with intravenous (IV) diuretic agents within 48 h of admission were identified. Patients were categorized into 1 of 4 mutually exclusive hierarchical treatment groups defined by complexity of treatment during hospitalization (intensified treatment with mechanical support or IV vasoactive therapy, IV diuretic therapy reinitiated after discontinuation for ≥1 day without intensified treatment, IV diuretic dose increase/combination diuretic treatment without intensified treatment or IV diuretic reinitiation, or uncomplicated). RESULTS: Of 22,677 patients hospitalized for HF with reduced ejection fraction (HFrEF), 66% had uncomplicated hospitalizations without escalation of treatment beyond initial IV diuretic therapy. Among 7,809 remaining patients, the highest level of therapy received was IV diuretic dose increase/combination diuretic treatment in 25%, IV diuretic reinitiation in 36%, and intensified therapy in 39%. Overall, 19% of all patients had reinitiation of IV diuretic agents (26% of such patients had multiple instances), 12% were simultaneously treated with multiple diuretics, and 61% were transitioned to oral diuretic agents before discharge. Compared with uncomplicated treatment, IV diuretic reinitiation and intensified treatment were associated with significantly longer median length of stay (uncomplicated: 4 days; IV diuretic reinitiation: 8 days; intensified: 10 days) and higher rates of in-hospital (uncomplicated: 1.6%; IV diuretic reinitiation: 4.2%; intensified: 13.2%) and 30-day post-discharge mortality (uncomplicated: 5.2%; IV diuretic reinitiation: 9.7%; intensified: 12.7%). CONCLUSIONS: In this contemporary real-world population of U.S. patients hospitalized for HFrEF, one-third of patients had in-hospital treatment escalated beyond initial IV diuretic therapy. These more complex treatment patterns were associated with highly variable patterns of diuretic use, longer hospital lengths of stay, and higher mortality. Standardized and evidence-based approaches are needed to improve the efficiency and effectiveness of in-hospital HFrEF care.

Utilization of palliative care services for cardiac arrest patients undergoing therapeutic hypothermia: A retrospective analysis.

BACKGROUND: Palliative care (PC) services are integral to the care of patients with advanced medical illnesses. Given the significant morbidity and mortality associated with cardiac arrest, we sought to measure the use and impact of PC in the care of patients treated with therapeutic hypothermia (TH). METHODS: We conducted a retrospective study of 317 consecutive patients undergoing TH after cardiac arrest. We compared intensive care unit (ICU) characteristics and clinical outcomes of subjects who received PC consultation (n=125) to those who did not (n=192). RESULTS: The proportion of TH patients with PC consultations increased to greater than 60% by 2013, corresponding to our institution's expansion of PC services, development of a dedicated PC unit, and integration of this service into our published TH protocol. In the TH population, time to return of spontaneous circulation (ROSC) was associated with higher inpatient mortality (p<0.001) and placement of a PC consult (p=0.011). TH patients who received PC consultation had longer ICU stays (p=0.034), more ventilator days (p<0.001), and higher inpatient mortality (p<0.001). When these measures were analyzed cohort-wide comparing all TH patients pre- and post-2013, at which time the frequency of PC consultation had dramatically increased, there were no statistically significant differences in ICU care or outcomes. CONCLUSION: In our population of cardiac arrest patients undergoing TH, the utilization of PC services has increased over time, particularly for those patients with high morbidity and mortality. Future randomized studies may further delineate optimal patient selection for PC consultation to better facilitate goals of care discussions and timely medical decision-making.

The lack of obstructive coronary artery disease on coronary CT angiography safely reduces downstream cost and resource utilization during subsequent chest pain presentations.

OBJECTIVE: The purpose of this study is to investigate the cost and resource use due to chest pain (CP) evaluations after initial coronary CT angiography (CCTA) stratified by coronary artery disease (CAD) burden. METHODS: We examined 1518 patients referred for CCTA from January 2005 to July 2012 for downstream evaluation after CCTA during a median follow-up of 351 days. Results were stratified by CAD burden as quantified on CCTA into no CAD, nonobstructive CAD (<50% stenosis), or obstructive CAD (≥50% stenosis). The incidence of ischemic testing at the time of recurrent evaluation (defined as a composite of clinic visit, emergency department encounter, or ischemic testing after the index CCTA for CP, atypical CP, or angina defined by ICD-9 code), the testing modality used, and frequency of testing were abstracted and used to calculate the direct costs of downstream utilization. Major adverse cardiovascular events defined as all-cause mortality, nonfatal myocardial infarction, stroke, or revascularization >90 days from CCTA were abstracted using ICD-9 codes and Social Security Death Index query. RESULTS: A total of 174 patients (11.5%) underwent evaluation for CP after index CCTA with a higher rate of subsequent clinical visits among obstructive CAD patients compared to those with nonobstructive CAD and no CAD (17.8% vs 13.9% vs. 7.5%; P < .001). A significant reduction in the incidence of repeat ischemic testing was observed in patients with no CAD and nonobstructive CAD (P = .002). This resulted in a lower per-patient cost in the nonobstructive CAD and no CAD patients (median [interquartile range 25-75]: $2952 [$307-2952] and $235 [$0-2880]) when compared with patients with obstructive CAD (median [interquartile range 25-75]: $5832 [$5498-17,459]; P < .001). Major adverse cardiovascular events were not different in the 90 patients that underwent repeat testing at the time of CP evaluation when compared with the 84 patients for whom testing was deferred. CONCLUSION: Absence of CAD on initial CCTA was associated with lower costs and decreased downstream utilization compared to the presence of nonobstructive and obstructive CAD on CCTA during median follow-up of 351 days.

Magneto-Fluorescent Carbon Nanotube-Mediated siRNA for Gastrin-Releasing Peptide Receptor Silencing in Neuroblastoma.

We demonstrate a newly-developed magneto-fluorescent carbon nanotube (CNT) mediated siRNA (CNT-siRNA) delivery system, which significantly silences our target of interest, gastrin-releasing peptide receptor (GRP-R), in neuroblastoma. CNT-siGRP-R resulted in a 50% silencing efficiency and a sustained efficacy of 9 days for one-time siRNA treatment in vitro, whereas siRNA delivered by the commercial transfection reagent couldn't knockdown GRP-R expression. We further show that CNT-siRNA efficiently inhibits the growth of subcutaneous xenograft tumors in vivo. This system allows us to track the CNT-siRNA distribution via both near-infrared fluorescence and magnetic resonance imaging. Moreover, our delivery system can be used to knockdown GRP-R expression in other cancer cell types, such as human breast cancer cells. The high efficiency and sustained efficacy may indicate that the natural stacking interactions between CNTs and siRNAs can protect siRNAs from degradation and enhance their stability during the delivery process.