Post-intensive cardiac care outpatient long-term outreach clinic (PICCOLO clinic): Defining health care needs and outcomes among coronary care unit survivors.

Objective: Patients who survive critical illness endure complex physical and mental health conditions, referred to as post-intensive care syndrome (PICS). The University of Michigan's post-intensive cardiac care outpatient long-term outreach (PICCOLO) clinic is designed for patients recently admitted to the coronary care unit (CCU). The long-term goal of this clinic is to understand post-CCU patients' needs and design targeted interventions to reduce their morbidity and mortality post-discharge. As a first step toward this goal, we aimed to define the post-discharge needs of CCU survivors. Design setting particpants: We retrospectively reviewed case-mix data (including rates of depression, PTSD, disability, and cognitive abnormalities) and health outcomes for patients referred to the PICCOLO clinic from July 1, 2018, through June 30, 2021 at Michigan Medicine. Results: Of the 134 referred patients meeting inclusion criteria, 74 (55 %) patients were seen in the PICCOLO clinic within 30 days of discharge. Patients seen in the clinic frequently screened positive for depression (PHQ-2 score ≥3, 21.4 %) and cognitive impairment (MOCA <26, 38.8 %). Further, patients also reported high rates of physical difficulty (mean WHODAS 2.0 score 28.4 %, consistent with moderate physical difficulty). Consistent with medical intensive care unit (ICU) patients, CCU survivors experience PICS. Conclusion: This work highlights the feasibility of an outpatient care model and the need to leverage information gathered from this care model to develop treatment strategies and pathways to address symptoms of PICS in CCU survivors, including depression, cognitive impairment, and physical disability.

A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia.

OBJECTIVES: Diagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. METHODS: We developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022-2023) and 5-year pre-intervention MVP controls (2017-2022). RESULTS: VAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122-131], post-intervention rate 102 [95% CI: 92-112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177-1205], post-intervention rate 1149 [95% CI: 1116-1184], p 0.03). DISCUSSION: Implementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted.

Implementation of a Nurse-Driven Spontaneous Awakening Trial Protocol in a Cardiac Intensive Care Unit.

BACKGROUND: In patients receiving mechanical ventilation, spontaneous awakening trials reduce morbidity and mortality when paired with spontaneous breathing trials. However, spontaneous awakening trials are not performed every day they are indicated and little is known about spontaneous awakening trial protocol use in cardiac intensive care units. LOCAL PROBLEM: Spontaneous awakening trial completion rate at the study institution was low and no trial protocol was regularly used. METHODS: A preintervention-postintervention retrospective cohort study was performed in adult patients with at least 24 hours of invasive mechanical ventilation in Michigan Medicine's cardiac intensive care unit. Patients with SARS-CoV-2 infection were excluded. Data included demographics, sedation, mechanical ventilation duration, and in-hospital mortality. A nurse-driven spontaneous awakening trial protocol modified for the cardiac intensive care unit was implemented in October 2020. RESULTS: Compared with the preintervention cohort (n = 29, May through July 2020), the postintervention cohort (n = 27, October 2020 through February 2021) had a higher ratio of number of trials performed to number of days eligible for trial (0.91 vs 0.52; P < .01). Median continuous sedative infusion duration was shorter after intervention (2.3 vs 3.6 days; P = .02). Median mechanical ventilation duration (3.8 vs 4.7 days; P = .18) and mortality (41% vs 41%; P = .95) were similar between groups. CONCLUSIONS: Spontaneous awakening trial protocol implementation led to a higher trial completion rate and a shorter duration of continuous sedative infusion. Larger studies are needed to assess the impact of protocolized spontaneous awakening trials on cardiac intensive care unit patient outcomes.

Integration of social media with targeted emails and in-person outreach for exception from informed consent community consultation.

BACKGROUND: Exception from informed consent (EFIC) enables the enrollment of research subjects with emergent conditions to clinical trials without prior consent. EFIC study approval requires community consultation and public disclosure. We hypothesized that the integration of social media with targeted emails and in-person outreach is an effective community consultation strategy. METHODS: We utilized social media with targeted emails and in-person outreach for the community consultation of the ACCESS cardiac arrest trial. Study advertisements were disseminated using Facebook and Instagram, and targeted emails were sent to emergency medicine, prehospital, and cardiology providers. We also interviewed at-risk individuals with cardiac conditions, their caretakers, and patient advocacy groups. Participants were asked to complete a survey about their opinions about the study. RESULTS: We collected 559 surveys over an 8-week period, and 70.5% of the surveys were obtained using social media. The median (IQR) age of survey respondents was 44 (33-57) years; 89.9% were White and 60.1% were women. A total of 91.3% believed ACCESS was an important study. Compared to the in-person group, more from social media (81.8% vs. 63.3%, p < 0.05) and targeted email (77.4% vs. 63.3%, p < 0.05) groups said they would include their loved ones in the study. More from the in-person group believed that their opinion would be considered seriously compared to the social media (75.9% vs. 62.6%, p < 0.05) and targeted email (75.9% vs. 54.5%, p < 0.05) groups. The incorporation of social media and targeted emails for community consultation reduced the cost per survey by fourfold compared to an in-person-only strategy. CONCLUSIONS: The integration of social media with targeted emails and in-person outreach was a feasible and cost-saving approach for EFIC community consultation. Future work is necessary to determine the perception and best utilization of social media for community consultation.

Impact of a pharmacist in an interdisciplinary post-cardiac intensive care unit clinic.

BACKGROUND: The complex needs of cardiac patients shortly after discharge from a cardiac intensive care unit (CICU) provides a unique opportunity for a pharmacist to help optimize medication management and guideline-directed medical therapy (GDMT). OBJECTIVE: This study describes the impact of a pharmacist in a multidisciplinary post-CICU clinic. METHODS: We performed a retrospective cohort study of patients ≥18 years of age who completed a visit in the University of Michigan Post Intensive Cardiac Care Outpatient Long-Term Outreach (PICCOLO) Clinic from July 2018 to May 2020. RESULTS: One hundred and six CICU survivors were referred. Of these 12 chose to follow-up with long term care providers. A total of 70 of the remaining 94 (74%) completed a visit. The median age was 65 (54-72) years, 71.4% were male, and 85.7% were Caucasian. The median number of pharmacist interventions at each visit was 4 (3-5), all patients had at least 1 intervention. Interventions included medication dose adjustment (n = 46); GDMT optimization (n = 42); medication change (n = 18); medication addition (n = 23) and cessation (n = 21); lab monitoring (n = 97); refill assistance (n = 16); pillbox provision (n = 8); and medication cost assistance (n = 8). CONCLUSIONS: Pharmacist led interventions in a post CICU clinic resulted in medication changes to optimize therapy, increased laboratory monitoring, medication cost savings for patients, and interventions to facilitate GDMT adherence.

Atypical Antipsychotic Safety in the CICU.

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Characteristics of Heart Failure Patients With or Without Hypotension When Transitioning From Nitroprusside to Sacubitril-Valsartan.

BACKGROUND: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction (HFrEF). Little is known about outcomes of HFrEF patients transitioned from sodium nitroprusside (SNP) to sacubitril-valsartan during an admission for acute decompensated heart failure. We sought to describe characteristics of patients initiated on sacubitril-valsartan while receiving SNP and, in particular, those patients who did and did not experience hypotension requiring interruption or discontinuation of sacubitril-valsartan. METHODS: We performed a retrospective case series of adult patients (>18 years) with HFrEF (left ventricular ejection fraction ≤40%) admitted to the University of Michigan cardiac intensive care unit between July 2018 to September 2020 who received sacubitril-valsartan while on SNP. RESULTS: A total of 15 patients with acute decompensated heart failure were initiated on sacubitril-valsartan while on SNP. The mean age was 57 ± 15.9 years. Seven (46.7%) patients experienced hypotension. The patients in the cohort who experienced hypotension were numerically older (60 ± 17 vs. 55 ± 15.5), and the majority were white (86%). Patients with hypotension had a numerically lower left ventricular ejection fraction (13 ± 4.2 vs. 18 ± 8.2) and higher serum creatinine (1.4 ± 0.54 vs. 0.88 ± 0.25). Seven (100%) patients received a diuretic on the day of sacubitril-valsartan initiation in those who experienced hypotension compared with 2 (25%) in those who did not experience hypotension. CONCLUSIONS: In almost half of patients admitted to the cardiac intensive care unit with acutely decompensated HFrEF, significant hypotension was seen when initiating sacubitril-valsartan while on SNP. Future studies should evaluate appropriate patients for this transition and delineate appropriate titration parameters.

Safety of dexmedetomidine in the cardiac intensive care unit.

AIMS: Dexmedetomidine is one of the sedative agents recommended by the Society of Critical Care Medicine as a preferred option over benzodiazepines in critically ill, mechanically ventilated patients. Little data exists describing sedation in the cardiac intensive care unit (CICU). The purpose of this study was to determine the prevalence of adverse events in CICU patients treated with dexmedetomidine. METHODS AND RESULTS: This was a retrospective cohort analysis of patients >18 years old admitted to the University of Michigan CICU from June 2014 to October 2019 who received dexmedetomidine therapy. The primary outcome was the composite of adverse events including bradycardia, hypotension, increasing vasopressor/inotrope requirements, and asystole. Secondary outcomes included individual components of the primary outcome. Patients that experienced adverse events were compared to those that did not experience adverse events to identify risk factors for adverse events. A total of 197 patients were included. There were 116 adverse events in 106 patients. Hypotension was the most common adverse event, making up 60.3% of adverse events reported. Increased vasopressor requirement and bradycardia both occurred in 22 patients (18.9%). Asystole occurred in two patients. B-type natriuretic peptide (BNP) levels were significantly higher in those experiencing an adverse event (848 pg/mL vs. 431 pg/mL; P = 0.03). CONCLUSIONS: Patients admitted to the CICU experienced a high rate of adverse events with dexmedetomidine use. Those experiencing adverse events were more likely to have a higher BNP. Future studies should explore the safety of alternative sedative agents to ascertain safe pharmacological options for patients admitted to the CICU.

Utilization of Cardiac Rehabilitation Among Cardiac Intensive Care Unit Survivors.

Cardiac rehabilitation (CR) is associated with decreased mortality and rehospitalization rates for patients with a variety of cardiac conditions. Although CR referral rates for STEMI patients have improved, rates for heart failure have remained low. Many of these patients are admitted to the cardiac intensive care unit (CICU). However, it is unknown how often CICU survivors qualify for cardiac rehabilitation, how often they are referred, and why eligible patients are not referred. This is a retrospective single-center study of 417 consecutive patients admitted to CICU for >48 hours from March 30, 2016 to March 30, 2017. We excluded patients with in-hospital mortality or those discharged AMA, to hospice or transferred. Chart abstraction was used to determine CR indications based on known American College of Cardiology/American Heart Association guidelines. If CR was indicated, medical records through September 2017 were reviewed to determine both referral and participation rates. In the absence of a referral, medical records were reviewed for potential barriers. A total of 296 CICU survivors were identified upon discharge with 185 (63%) having guideline-directed indications for CR referral. The most common indications were heart failure with reduced ejection fraction (HFrEF, 38%), cardiothoracic surgery (26%), and STEMI (23%). Upon discharge, only 30% of patients were referred to CR. The referral rate increased by 33% to 63% by 18 months postdischarge. CR referrals were most frequently placed following STEMI (91%), NSTEMI (80%), and postpercutaneous coronary intervention (80%). Only 35% of HFrEF discharges were referred to CR. Of patients not referred to CR, no explanation for a lack of referral was documented 87% of the time. In conclusion, nearly 2 of 3 patients discharged from the CICU had CR indications, most commonly HFrEF. CR referrals are frequently not placed and reason for nonreferral is rarely documented. CICU admission may provide a defined event to prompt referral.

Percutaneous coronary intervention strategies in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease.

PURPOSE OF REVIEW: This review aims to summarize recent reports on percutaneous coronary intervention (PCI) strategies for patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). RECENT FINDINGS: Recent randomized clinical trials and meta-analyses have suggested that patients with STEMI and multivessel CAD may benefit more from multivessel PCI (either multivessel primary PCI or staged PCI before hospital discharge) than culprit vessel-only primary PCI. These reports have changed clinical practice guideline recommendations that now conclude that multivessel PCI may be considered in selected hemodynamically stable patients with significant noninfarct artery stenoses based on anatomic criteria alone. Fractional flow reserve measurement can document functional significance in nonculprit stenoses, but fractional flow reserve-guided PCI has not been shown to impact mortality or myocardial infarction rates. Additionally, nonculprit artery chronic total occlusion PCI was not effective in improving left ventricular function in one randomized trial. SUMMARY: Multivessel primary PCI or staged PCI is effective and safe in selected patients with STEMI and multivessel coronary disease. Future randomized controlled trials are needed to define the optimal timing of multivessel PCI, as well as the appropriate use of PCI in nonculprit stenoses.

Temporal trends in peripheral arterial interventions: Observations from the blue cross blue shield of michigan cardiovascular consortium (BMC2 PVI).

OBJECTIVES: The aim is to examine trends in procedural indication, arterial beds treated, and device usage in peripheral arterial interventions (PVIs). BACKGROUND: There is little data on indication, vascular beds treated and devices utilized for peripheral arterial interventions. METHODS: We used data from 43 hospitals participating in the BMC2 VIC registry. PVIs were separated by year and divided by arterial segment. Lower extremity PVIs were subclassified as having been performed for claudication or critical limb ischemia (CLI). Yearly device usage was also included. A repeated measure ANOVA was used to determine trends. RESULTS: 44,650 PVIs were performed from 2006 to 2013. Renal interventions decreased from 18% of interventions in 2006 to 5.6% in 2013 (P < 0.001) and femoral-popliteal increased from 54.9% in 2006 to 64.5% in 2013 (P < 0.001). No significant trend was seen for aorta-iliac or below-the-knee interventions. 58.6% of PVIs were performed for claudication in 2006 and this decreased to 44.6% in 2013 (P = 0.025). Indications for CLI were 24.1% in 2006 and 47.5% in 2013 (P < 0.001). There were significant increases in the use of balloon angioplasty (P = 0.029) and cutting/scoring balloons (P < 0.001) while cryoballoon usage decreased (P < 0.001). No significant changes were found with stenting, atherectomy, and laser. CONCLUSIONS: There is a significant increase in patients presenting with CLI. Renal artery intervention rates are decreasing while femoral-popliteal interventions are increasing. Additionally, balloon angioplasty and cutting/scoring balloon usage is increasing. © 2017 Wiley Periodicals, Inc.

Update on primary PCI for patients with STEMI.

Primary PCI is the dominant reperfusion strategy for patients with ST-elevation myocardial infarction and continues to evolve. The purpose of this review is to summarize recent reports that focused on the relationship of door-to-balloon time with mortality, radial versus femoral artery access, aspiration thrombectomy, culprit versus multivessel primary PCI, drug-eluting stents, and anticoagulation and antiplatelet therapies.

Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point.

Recurrent mutations in the spliceosome are observed in several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of the branch point sequence (BPS) during selection of the 3' splice site (ss) in RNA splicing. Here, we report that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3' ss selection as the most frequent splicing defect. Strikingly, mutant SF3B1 utilizes a BPS that differs from that used by wild-type SF3B1 and requires the canonical 3' ss to enable aberrant splicing during the second step. Approximately 50% of the aberrantly spliced mRNAs are subjected to nonsense-mediated decay resulting in downregulation of gene and protein expression. These findings ascribe functional significance to the consequences of SF3B1 mutations in cancer.

Percutaneous Coronary Intervention Utilization and Appropriateness across the United States.

BACKGROUND: Substantial geographic variation exists in percutaneous coronary intervention (PCI) use across the United States. It is unclear the extent to which high PCI utilization can be explained by PCI for inappropriate indications. The objective of this study was to examine the relationship between PCI rates across regional healthcare markets utilizing hospital referral regions (HRRs) and PCI appropriateness. METHODS: The number of PCI procedures in each HRR was obtained from the 2010 100% Medicare limited data set. HRRs were divided into quintiles of PCI utilization with increasing rates of utilization progressing to quintile 5. NCDR CathPCI Registry® data were used to evaluate patient characteristics, appropriate use criteria (AUC), and outcomes across the HRR quintiles defined by PCI utilization with the study population restricted to HRRs where ≥ 80% of the PCIs were performed at institutions participating in the registry. PCI appropriateness was defined using 2012 AUC by the American College of Cardiology (ACC)/American Heart Association (AHA)/The Society for Cardiovascular Angiography and Interventions (SCAI). RESULTS: Our study cohort comprised of 380,981 patients treated at 178 HRRs. Mean PCI rates per 1,000 increased from 4.6 in Quintile 1 to 10.8 in Quintile 5. The proportion of non-acute PCIs was 27.7% in Quintile 1 increasing to 30.7% in Quintile 5. Significant variation (p < 0.001) existed across the quintiles in the categorization of appropriateness across HRRs of utilization with more appropriate PCI in lower utilization areas (Appropriate: Q1, 76.53%, Q2, 75.326%, Q3, 75.23%, Q4, 73.95%, Q5, 72.768%; Inappropriate: Q1 3.92%, Q2 4.23%, Q3 4.32%, Q4 4.35%, Q5 4.05%; Uncertain: Q1 8.29%, Q2 8.84%, Q3 8.08%, Q4 9.01%, Q5 8.93%; Not Mappable: Q1 11.26%, Q2 11.67%, Q3 12.37%, Q4 12.69%, Q5 14.34%). There was no difference in risk-adjusted mortality across quintiles of PCI utilization. CONCLUSIONS: Geographic regions with lower PCI rates have a higher proportion of PCIs performed for appropriate indications. Areas that perform more PCIs also appear to perform more elective PCI and many could not be mapped by the AUC.

Cor triatriatum: a reversible cause of severe pulmonary hypertension.

Cor triatriatum sinister is a congenital heart disorder that can lead to progressive dyspnea, pulmonary hypertension, and ultimately right ventricular (RV) failure. We report a case in which symptoms of progressive pulmonary hypertension were initially attributed to asthma, leading to a delayed diagnosis that resulted in suprasystemic pulmonary pressures and RV dysfunction. Rapid symptomatic and hemodynamic improvement was observed after surgical repair, with normalization of pulmonary artery pressures and RV function.

Acute necrotizing eosinophilic myocarditis in a patient taking Garcinia cambogia extract successfully treated with high-dose corticosteroids.

A previously healthy 48-year-old woman was evaluated for lightheadedness and chest heaviness 2 weeks after starting the herbal supplement Garcinia cambogia. She was found to be hypotensive and had an elevated serum troponin level. The patient had a progressive clinical decline, ultimately experiencing fulminant heart failure and sustained ventricular arrhythmias, which required extracorporeal membrane oxygenation support. Endomyocardial biopsy results were consistent with acute necrotizing eosinophilic myocarditis (ANEM). High-dose corticosteroids were initiated promptly and her condition rapidly improved, with almost complete cardiac recovery 1 week later. In conclusion, we have described a case of ANEM associated with the use of Garcinia cambogia extract.

Nedd8-activating enzyme inhibitor MLN4924 provides synergy with mitomycin C through interactions with ATR, BRCA1/BRCA2, and chromatin dynamics pathways.

MLN4924 is an investigational small-molecule inhibitor of the Nedd8-activating enzyme currently in phase I clinical trials. MLN4924 induces DNA damage via rereplication in most cell lines. This distinct mechanism of DNA damage may affect its ability to combine with standard-of-care agents and may affect the clinical development of MLN4924. As such, we studied its interaction with other DNA-damaging agents. Mitomycin C, cisplatin, cytarabine, UV radiation, SN-38, and gemcitabine demonstrated synergy in combination with MLN4924 in vitro. The combination of mitomycin C and MLN4924 was shown to be synergistic in a mouse xenograft model. Importantly, depletion of genes within the ataxia telangiectasia and Rad3 related (ATR) and BRCA1/BRCA2 pathways, chromatin modification, and transcription-coupled repair reduced the synergy between mitomycin C and MLN4924. In addition, comet assay demonstrated increased DNA strand breaks with the combination of MLN4924 and mitomycin C. Our data suggest that mitomycin C causes stalled replication forks, which when combined with rereplication induced by MLN4924 results in frequent replication fork collisions, leading to cell death. This study provides a straightforward approach to understand the mechanism of synergy, which may provide useful information for the clinical development of these combinations.