Faculty Bibliography

IMPORTANCE/UNASSIGNED:The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance. OBJECTIVE/UNASSIGNED:To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was an international, multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial including patients implanted with a de novo HM3 LVAD across 51 centers. Data analysis was conducted from April to July 2024. INTERVENTIONS/UNASSIGNED:Patients were randomized in a 1:1 ratio to receive aspirin (100 mg per day) or placebo, in addition to a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2 to 3 in both groups. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary end point (assessed for noninferiority) was a composite of survival free of any nonsurgical (>14 days after implant) HRAEs including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at 12 months. Secondary end points included nonsurgical bleeding, stroke, and pump thrombosis events. RESULTS/UNASSIGNED:Among 589 of 628 patients (mean [SD] age, 57.1 [13.7] years; 456 male [77.4%]) who contributed to the primary end point analysis, a history of PCI, CABG, stroke, or PVD was present in 41% (240 of 589 patients). There was no interaction between the presence of an atherosclerotic vascular condition and effect of aspirin compared with placebo (P for interaction= .23). The preset 10% noninferiority margin was not crossed for the studied subgroup of patients. Thrombotic events were rare, with no differences between aspirin and placebo in patients with and without vascular disease (P for interaction = .77). Aspirin treatment was associated with a higher rate of nonsurgical major bleeding events in the group with prior vascular condition history compared with those without aspirin (rate ratio for placebo compared with aspirin, 0.52; 95% CI, 0.35-0.79). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Results of this prespecified analysis of the ARIES-HM3 randomized clinical trial demonstrate that in patients with advanced heart failure who have classical indications for antiplatelet therapy use at the time of LVAD implantation, aspirin avoidance was safe and not associated with increased thrombosis risk. Importantly, elimination of aspirin was associated with no increased thrombosis but a reduction in nonsurgical bleeding events in patients with a history of PCI, CABG, stroke, or PVD. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04069156.

BACKGROUND AND AIMS/OBJECTIVE:Patients with acute myocardial infarction (AMI) who require invasive mechanical ventilation (IMV) represent a critically ill population with limited data on optimal sedative and analgesic use. Clinical trials assessing dexmedetomidine use exclude or poorly represent patients with AMI. This study aimed to compare the use of early sedation with dexmedetomidine to usual-care sedation in patients with AMI requiring IMV. METHODS:We utilized the Vizient® Clinical Data Base to identify patients aged ≥18 years admitted between 2015 and 2019 with a primary diagnosis of AMI who required IMV. Patients receiving dexmedetomidine on the first day of IMV were included in the early dexmedetomidine group while the remaining patients were assigned to the usual care group. Inverse probability of treatment weighting (IPTW) was used to estimate adjusted risk differences between groups. RESULTS:We identified 15,928 patients, of which 1,620 (10.2%) received early dexmedetomidine. Patients who received early dexmedetomidine were more likely to present with cardiogenic shock (52.0% vs. 47.7%, P=0.001). In unadjusted analyses, patients receiving early dexmedetomidine had lower in-hospital mortality (33.0% vs 42.1%) and more ventilator-free days (13.6 vs 12.1) compared to usual care (both, P<0.05). After IPTW, patients receiving early dexmedetomidine had a 11.0% (95% confidence interval [CI]: 8.6% to 13.5%) lower mortality and more ventilator-free days (mean difference: +2.2 days, 95% CI: 1.6-2.8 days). CONCLUSION/CONCLUSIONS:Early sedation with dexmedetomidine was associated with lower mortality compared to usual care in patients with AMI requiring IMV. A randomized controlled trial of sedative agents in this population is warranted.

Cardiogenic shock (CS) is a complex, multisystem disorder precipitated by hypoperfusion from cardiac dysfunction. Our current approach to defining and treating CS encompasses all patients under 1 umbrella regardless of phenotype. This has created challenges for clinical trials and patient care owing to the heterogeneity of the patient population with CS. The Society of Coronary Angiography and Interventions shock classification has created a universal language for CS that has been rapidly adopted by researchers and clinicians. Its latest iteration established the 3-axis model incorporating shock severity, risk modifiers, and phenotypes. Phenotypes of CS have unique hemodynamic profiles that require nuanced adjustment approaches. In this study, we discuss representative cases including acute myocardial infarction, acute-on-chronic heart failure, fulminant myocarditis, and right ventricular failure. For each phenotype, specific hemodynamic parameters may help confirm appropriate diagnosis and direct to therapeutic targets signaling stability and recovery. The underlying pathophysiology of each phenotype can also help predict the extent of stabilization with pharmacologic interventions or the need to escalate to mechanical circulatory support. In conclusion, this tailored approach to CS, rather than a 1-size-fits-all approach, could help improve outcomes.

IMPORTANCE/UNASSIGNED:Few person-centered, scalable models of collaborative intensive care unit (ICU) clinician-palliative care specialist care exist. OBJECTIVE/UNASSIGNED:To evaluate the effect of a collaborative palliative care intervention compared to usual care among family members of patients in the ICU. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This parallel-group randomized clinical trial with patient-level randomization was conducted between April 2021 and September 2023. The study was set at 6 medical and surgical ICUs in 1 academic hospital and 1 community hospital. The study participants included critically ill older adult patients with 1 of 11 poor outcome phenotypes, their family members with elevated palliative care needs, and their attending ICU physicians. INTERVENTION/UNASSIGNED:An automated electronic health record-integrated, mobile application-based communication platform that displayed family-reported needs over 7 days, coached ICU attending physicians on addressing needs, and prompted palliative care consultation if needs were not reduced within 3 study days. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was change in the family-reported Needs at the End-of-Life Screening Tool (NEST) score between study days 1 and 3. The 13-item NEST score is a number between 0 and 130, with higher scores indicating a greater need. Secondary outcomes included quality of communication and goal of care concordance, as well as 3-month psychological distress. RESULTS/UNASSIGNED:Of 151 family members, the mean (SD) age was 57.4 (12.9) years, and 110 (72.9%) were female. Of 151 patients, the mean (SD) age was 69.8 (9.7) years, and 86 (57.0%) were male. Thirty-five ICU physicians were male (68.6%). Seventy-six patients were randomized to the intervention group and 75 to the control group. Treatment group differences in estimated mean NEST scores were similar at 3 days between the intervention and control groups (-3.1 vs -2.0, respectively; estimated mean difference in differences, -1.3 points [95% CI, -6.0 to 3.5]) and 7 days (-2.3 vs -2.2, respectively; estimated mean difference in differences, 0 points [95% CI, -6.2 to 6.2]). Median (IQR) need scores were lower among individuals who remained in the ICU at day 3 for intervention participants vs controls (24.5 [16.5-34.5] vs 27.5 [13.0-40.0], respectively); median (IQR) need scores were also lower among those who remained in the ICU at day 7 for intervention vs controls (22.0 [11.0-35.0] vs 28.0 [14.0-35.0], respectively). Goal concordance, quality of communication, and psychological distress symptoms did not differ. Twenty-nine intervention participants (38.2%) had palliative care consultations, compared to only 3 (4.0%) among controls, (P < .001); 66 intervention participants (87.0%) had a family meeting, compared to 48 (64.0%) among controls (P = .001). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial, a collaborative, person-centered, ICU-based palliative care intervention had no effect on palliative care needs or psychological distress compared to usual care despite a higher frequency of palliative care consultations and family meetings among intervention participants. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04414787.

BACKGROUND:Implantable cardioverter-defibrillator (ICD) shocks are a common complication after left ventricular assist device (LVAD) implantation; however, data on their frequency and causes are limited. OBJECTIVE:The purpose of this study was to define the incidence, programming, patient characteristics, and factors associated with appropriate and inappropriate ICD shocks in persons with LVADs. METHODS:We performed a retrospective review at Duke University Hospital of all LVAD recipients implanted between January 1, 2013, to June 30, 2019, with a preexisting ICD. ICD shocks were adjudicated by the treating physician and a second reviewer for the purpose of this study. RESULTS:Among 421 patients with an ICD in situ undergoing LVAD implant, 147 (33.9%) had at least 1 shock after LVAD implantation. Among 134 patients with complete device history, a total of 330 shock episodes occurred: 255 (77.3%) appropriate and 75 (22.7%) inappropriate. Etiologies for inappropriate shocks included supraventricular tachycardia (n = 66 [20.0%]), physiological oversensing (n = 1 [0.3%]), and nonphysiological oversensing (n = 8 [2.4%]) including LVAD electromagnetic interference (n = 1 [0.3%]). ICD programming with shorter detection delay (P <.001) and absence of antitachycardia pacing programming (P = .001) in high-rate zones was seen more commonly in inappropriate shock than appropriate shock. CONCLUSIONS:The rate of inappropriate shocks in LVAD recipients is very high and most often is due to supraventricular arrhythmias. LVAD electromagnetic interference is a rare cause of ICD shock. Implementation of current consensus American Heart Association recommendations for LVAD programming with long detection delays and high rate cutoffs may help prevent inappropriate ICD shocks.

OBJECTIVE/UNASSIGNED:There is a paucity of data assessing the impact of nutritional status on outcomes in patients supported with the HeartMate 3 (HM3) left ventricular assist device (LVAD). METHODS/UNASSIGNED:Patients ≥18 years of age who underwent HM3 LVAD implantation between 2015 and 2020 were identified from a single tertiary care center. The primary outcome assessed was death or device replacement. A secondary outcome of driveline infection was also evaluated. Kaplan-Meier survival analysis and a multivariate Cox-proportional hazards model were used to identify predictors of outcome. RESULTS/UNASSIGNED: < .01). CONCLUSIONS/UNASSIGNED:Preoperative PNI scores may independently predict mortality and the need for device replacement in patients with HM3 LVAD. Routine use of the PNI score during preoperative evaluation and, when possible, supplementation to PNI >33, may be of value in this population.

BACKGROUND:It is common for clinicians to use the pulmonary artery diastolic pressure (PADP) as a surrogate for the pulmonary capillary wedge pressure (PCWP). Here, we determine the validity of this relationship in patients with various phenotypes of cardiogenic shock (CS). METHODS AND RESULTS/RESULTS:In this analysis of the Critical Care Cardiology Trials Network registry, we identified 1225 people admitted with CS who received pulmonary artery catheters. Linear regression, Bland-Altman and receiver operator characteristic analyses were performed to determine the strength of the association between PADP and PCWP in patients with left-, right-, biventricular, and other non-myocardia phenotypes of CS (eg, arrhythmia, valvular stenosis, tamponade). There was a moderately strong correlation between PADP and PCWP in the total population (r = 0.64, n = 1225) and in each CS phenotype, except for right ventricular CS, for which the correlation was weak (r = 0.43, n = 71). Additionally, we found that a PADP ≥ 24 mmHg can be used to infer a PCWP ≥ 18 mmHg with ≥ 90% confidence in all but the right ventricular CS phenotype. CONCLUSIONS:This analysis validates the practice of using PADP as a surrogate for PCWP in most patients with CS; however, it should generally be avoided in cases of right ventricular-predominant CS.

OBJECTIVE:To evaluate the effects of droxidopa or atomoxetine on intravenous (IV) vasoactive agent discontinuation in cardiothoracic intensive care unit (ICU) patients with hypotension refractory to midodrine. DESIGN/METHODS:Single-center, retrospective cohort study. SETTING/METHODS:Tertiary- and quaternary-care university teaching hospital. PARTICIPANTS/METHODS:Included patients who received at least 4 consecutive doses of droxidopa or atomoxetine and remained on concurrent midodrine. Patients were excluded if they received study medication before admission, had clinical deterioration after study medication initiation requiring additional vasoactives/escalation of IV vasoactive dosage for at least 12 hours, had a diagnosis of hepatorenal syndrome, were prisoners, or were pregnant. INTERVENTIONS/METHODS:Droxidopa, atomoxetine, or both. MEASUREMENTS AND MAIN RESULTS/RESULTS:The primary endpoint was time to discontinuation of IV vasoactive agents after initiation of study medication, analyzed using a Kaplan-Meier estimate with the Wilcoxon method, censoring death within 24 hours of the last dose of study medication. No adjustment for repetitive analyses was made, as the analysis was hypothesis-generating. Of the 72 charts reviewed, 45 patients met inclusion criteria (18 atomoxetine, 17 droxidopa, and 10 both). There were no differences in median time to discontinuation of IV vasoactive agents (21.9 days v 8.0 days v 13.9 days, respectively; p = 0.259) or ICU or hospital length of stay between groups. A higher percentage of patients who survived to hospital discharge received both study medications or droxidopa alone (90% v 76.5%) than atomoxetine alone (44.4%, p = 0.028). CONCLUSIONS:Droxidopa and atomoxetine are oral vasoactive agents with potential mechanisms to facilitate IV vasopressor weaning for patients in the ICU with hypotension refractory to midodrine, but further prospective research is needed.

Clinical practice in the contemporary cardiac intensive care unit (CICU) has evolved significantly over the last several decades. With more frequent multisystem organ failure, increasing use of advanced respiratory support, and the advent of new mechanical circulatory support platforms, clinicians in the CICU are increasingly managing patients with complex comorbid disease in addition to their high-acuity cardiovascular illnesses. Here, the authors discuss challenges associated with traditional trial design in the CICU setting and review novel clinical trial designs that may facilitate better evidence generation in the CICU.