Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.

Advancing the care of individuals with cancer through innovation & technology: Proceedings from the cardiology oncology innovation summit 2020 and 2021.

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era.

Novel Application of a Dynamic, In-room Survey Platform to Measure Surgical Team Satisfaction.

OBJECTIVE: To elucidate the potential usage of continuous feedback regarding team satisfaction and correlations with operative performance and patient outcomes. BACKGROUND: Continuous, actionable assessment of teamwork quality in the operating room (OR) is challenging. This work introduces a novel, data-driven approach to prospectively and dynamically assess health care provider satisfaction with teamwork in the OR. METHODS: Satisfaction with teamwork quality for each case was assessed utilizing a validated prompt displayed on HappyOrNot Terminals placed in all ORs, with separate panels for circulators, scrub nurses, surgeons, and anesthesia providers. Responses were cross-referenced with OR log data, team familiarity indicators, efficiency parameters, and patient safety indicator events through continuous, semiautomated data marts. Deidentified responses were analyzed through logistic regression modeling. RESULTS: Over a 24-week period, 4123 responses from 2107 cases were recorded. The overall response rate per case was 32.5%. Greater scrub nurse specialty experience was strongly associated with satisfaction (odds ratio: 2.15, 95% CI: 1.53-3.03, P < 0.001). Worse satisfaction was associated with longer than expected procedure time (odds ratio: 0.91, 95% CI: 0.82-1.00, P = 0.047), nighttime (0.67, 95% CI: 0.55-0.82, P < 0.001), and add-on cases (0.72, 95% CI: 0.60-0.86, P < 0.001). Higher material costs (22%, 95% CI: 6-37, P = 0.006) were associated with greater team satisfaction. Cases with superior teamwork ratings were associated with a 15% shorter length of hospital stay (95% CI: 4-25, P = 0.006). CONCLUSIONS: This study demonstrates the feasibility of a dynamic survey platform to report actionable health care provider satisfaction metrics in real-time. Team satisfaction is associated with modifiable team variables and some key operational outcomes. Leveraging qualitative measurements of teamwork as operational indicators may augment staff engagement and measures of performance.

Operative Team Familiarity and Specialization at an Academic Medical Center.

OBJECTIVE: To propose a framework for quantification of surgical team familiarity. BACKGROUND: Operating room (OR) teamwork quality is associated with familiarity among team members and their individual specialization. We describe novel measures of OR team familiarity and specialty experience. METHODS: Surgeon-scrub (SS) and surgeon-circulator (SC) teaming scores, defined as the pair's proportion of interactions relative to the surgeon's total cases in the preceding 6 months were calculated between 2017 and 2021 at an academic medical center. Nurse service-line (SL) experience scores were defined as the proportion of a nurse's cases performed within the given specialty. SS, SC, and nurse-SL scores were analyzed by specialty, case urgency, robotic approach, and surgeon academic rank. Two-sample Kolmogorov-Smirnov tests were used to determine heterogeneity between distributions. RESULTS: A total of 37,364 operations involving 150 attending surgeons and 222 nurses were analyzed. Median SS and SC scores were 0.08 (interquartile range: 0.03-0.19) and 0.06 (interquartile range: 0.03-0.13), respectively. Higher margin SLs, senior faculty rank, elective, and robotic cases were associated with greater SS, SC, and nurse-SL scores ( P <0.001). CONCLUSIONS: These novel measures of teaming and specialization illustrate the low levels of OR team familiarity and objectively highlight differences that necessitate a deliberate evaluation of current OR scheduling practices.

Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis: Report from an international registry.

PURPOSE: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis. METHODS: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram. RESULTS: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057). CONCLUSION: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis.

CD-19 CART therapy and orthostatic hypotension: a single center retrospective cohort study.

BACKGROUND: Chimeric antigen receptor T-cell (CART) therapy is a form of cellular immunotherapy used to treat hematologic malignancies. Major adverse cardiovascular events have been seen in CART patients who have high grade CRS, higher baseline creatinine, and troponin elevation. However, the incidence and factors associated with orthostatic hypotension after CART therapy have not previously been reported in the literature. METHODS: We looked at patients who underwent CD-19 directed CART therapy at UPMC Shadyside hospital from April 1st 2018 to December 1st 2020. Patients were classified as having orthostatic hypotension if they had recorded orthostatic vital signs that were positive or provider notes indicated that vitals had been taken and were positive in the time period from discharge to 3 months post-CART. Data was analyzed with univariate and multivariate analysis using logistic regression. RESULTS: 79% of patients had orthostatic hypotension after discharge from their CART hospitalization and 64% of those patients were symptomatic. Older age, lower BMI, lower ambulatory diastolic blood pressure and grade 2 CRS were associated with orthostatic hypotension in the univariate analysis. Older age and lower ambulatory systolic blood pressure were associated with orthostatic hypotension in the multivariate analysis. Symptomatic orthostatic hypotension was associated with a history of hypertension in both the univariate and multivariate analysis. Patients with symptoms also had a higher pre-CART ejection fraction but this association was not seen in the regression model. CONCLUSION: There is a high incidence of orthostatic hypotension after CART therapy even after discharge. Therefore, orthostatic vitals signs and associated symptoms should be assessed in both the inpatient and outpatient setting. Older patients and patients with lower BMIs, lower ambulatory blood pressures, grade 2 CRS, or a history of hypertension may need closer monitoring.

Improving Code Status Documentation Rates Using Communication Skills Training in Vascular Surgery: A Quality Improvement Initiative.

Introduction: Code status discussions are poorly understood by patients and variably performed by admitting providers, yet they are used as a quality metric. Surgical specialties, such as Vascular Surgery, admit patients with urgent and life-threatening illness. Surgical trainees are less likely to receive communication skills interventions when compared with nonsurgical specialties. Without a documented code status, nurses and physicians lack guidance on patient preference in the case of cardiopulmonary arrest and may deliver unwanted measures, which may also result in poor outcomes. Methods: We conducted a before-after Plan-Do-Study-Act quality improvement project between May 2018 and May 2019. A needs assessment included baseline code status documentation rates for the Vascular Surgery department admissions. A communication skills training (CST) and documentation intervention was provided to all Vascular Surgery trainees and advance practice providers (APPs). Departmental e-mails were sent over the 12-month intervention period, which demonstrated the code status documentation rates and served as reminders to document code status. Results: A total of 29 vascular surgery trainees and APPs received the intervention. At completion of the intervention, learners reported increased comfort initiating a code status discussion, making a recommendation for cardiopulmonary resuscitation (CPR) status, and having a strategy to discuss code status. A total of 2762 patient admissions were reviewed, with 1562 patient admissions occurring during the 12-month intervention period. The average code status documentation rate for the three months before the intervention was 7.8%. At the end of the 12-month intervention, documentation rates were 44.9% and 6 months after completion of the study period, average rates remained 45.2%. There was no change in admission rates during the study period. Discussion: CST and regular reminders increased vascular surgery residents' and APPs' comfort in engaging in code status discussions. After intervention, documentation of code status discussions increased with persistence up to six months after the intervention.

A new classification of cardio-oncology syndromes.

Increasing evidence suggests a multifaceted relationship exists between cancer and cardiovascular disease (CVD). Here, we introduce a 5-tier classification system to categorize cardio-oncology syndromes (COS) that represent the aspects of the relationship between cancer and CVD. COS Type I is characterized by mechanisms whereby the abrupt onset or progression of cancer can lead to cardiovascular dysfunction. COS Type II includes the mechanisms by which cancer therapies can result in acute or chronic CVD. COS Type III is characterized by the pro-oncogenic environment created by the release of cardiokines and high oxidative stress in patients with cardiovascular dysfunction. COS Type IV is comprised of CVD therapies and diagnostic procedures which have been associated with promoting or unmasking cancer. COS Type V is characterized by factors causing systemic and genetic predisposition to both CVD and cancer. The development of this framework may allow for an increased facilitation of cancer care while optimizing cardiovascular health through focused treatment targeting the COS type.

Case Report: Single Dose Anti-PD1 in a Patient With Metastatic Melanoma and Cardiac Allograft.

Background: Immune-checkpoint inhibition has improved outcomes in metastatic melanoma. However, limited data describes the safety and efficacy of this treatment in the setting of cardiac allograft. Emerging translational and clinical evidence suggests that the majority of the benefit from these therapies is driven by the initial dose(s), and that attenuated dosing schedules may be as effective as continuous treatment. Case presentation: We present a case vignette of a cardiac transplant recipient with metastatic melanoma who experienced six months of clinical benefit after one dose of pembrolizumab and did not suffer allograft rejection. Conclusion: This case adds to the current available literature on the administration of checkpoint inhibitors in patients with cardiac allografts. Further, it explores potential markers of immunotherapy response and supports the potential of shorter or individualized immune-checkpoint blockade dosing strategies.

Standardization of Inpatient CPR Status Discussions and Documentation Within the Division of Hematology-Oncology at UPMC Shadyside: Results From PDSA Cycles 1 and 2.

PURPOSE: In December 2016, 49% of patients admitted to inpatient oncology services at University of Pittsburgh Medical Center Shadyside Hospital had cardiopulmonary resuscitation (CPR) status discussion documentation before discharge. The aim of this project was to improve the rate of CPR status conversations. METHODS: During Plan-Do-Study-Act (PDSA) cycle 1, a stakeholder workgroup was formed in January 2017 by oncology faculty, fellows, nurses, advance practice providers (APPs), medicine housestaff, and palliative care faculty. All oncology clinicians and inpatient team members were reminded weekly to discuss and document CPR status preferences. APPs received training on efficient and effective CPR status assessment from palliative care faculty. Oncology leadership received monthly e-mail updates of CPR status documentation rates and endorsed CPR status best practice guidelines. For PDSA cycle 2, patient charts without CPR status documentation in March 2018 were reviewed, and themes were shared with oncology leadership and reviewed with APPs. RESULTS: After PDSA cycle 1, CPR status assessment rates increased from 49% to greater than 80%. In 2017, more than 1,500 more CPR status discussions were documented than in 2016. The percentage of patients discharged with "comfort measures only" or "do not resuscitate" orders increased from 14.2% (95% CI, 9.5% to 19.0%) to 19.8% (95% CI, 15.6% to 24.0%). For PDSA cycle 2, charts of 60 patients without CPR assessment were reviewed. Of these, 52% were admitted overnight by nocturnists and 48% by daytime APPs. Fifty-five percent of patients (n = 33 of 60) had metastatic disease. CPR status was documented on previous admissions for 53% of patients (n = 31 of 60) in the past 12 months. Fifteen percent (n = 11 of 60) were admitted for scheduled inpatient chemotherapy. CONCLUSION: A multipronged approach significantly increased CPR status assessments. More patients transitioned to comfort measures only or do not resuscitate when their preferences were clearly assessed and documented.

Myocardial extravascular extracellular volume fraction measurement by gadolinium cardiovascular magnetic resonance in humans: slow infusion versus bolus.

BACKGROUND: Myocardial extravascular extracellular volume fraction (Ve) measures quantify diffuse fibrosis not readily detectable by conventional late gadolinium (Gd) enhancement (LGE). Ve measurement requires steady state equilibrium between plasma and interstitial Gd contrast. While a constant infusion produces steady state, it is unclear whether a simple bolus can do the same. Given the relatively slow clearance of Gd, we hypothesized that a bolus technique accurately measures Ve, thus facilitating integration of myocardial fibrosis quantification into cardiovascular magnetic resonance (CMR) workflow routines. Assuming equivalence between techniques, we further hypothesized that Ve measures would be reproducible across scans. METHODS: In 10 volunteers (ages 20-81, median 33 yr, 3 females), we compared serial Ve measures from a single short axis slice from two scans: first, during a constant infusion, and second, 12-50 min after a bolus (0.2 mmol/kg gadoteridol) on another day. Steady state during infusion was defined when serial blood and myocardial T1 data varied <5%. We measured T1 on a 1.5 T Siemens scanner using a single-shot modified Look Locker inversion recovery sequence (MOLLI) with balanced SSFP. To shorten breath hold times, T1 values were measured with a shorter sampling scheme that was validated with spin echo relaxometry (TR = 15 sec) in CuSO4-Agar phantoms. Serial infusion vs. bolus Ve measures (n = 205) from the 10 subjects were compared with generalized estimating equations (GEE) with exchangeable correlation matrices. LGE images were also acquired 12-30 minutes after the bolus. RESULTS: No subject exhibited LGE near the short axis slices where Ve was measured. The Ve range was 19.3-29.2% and 18.4-29.1% by constant infusion and bolus, respectively. In GEE models, serial Ve measures by constant infusion and bolus did not differ significantly (difference = 0.1%, p = 0.38). For both techniques, Ve was strongly related to age (p < 0.01 for both) in GEE models, even after adjusting for heart rate. Both techniques identically sorted older individuals with higher mean Ve values. CONCLUSION: Myocardial Ve can be measured reliably and accurately 12-50 minutes after a simple bolus. Ve measures are also reproducible across CMR scans. Ve estimation can be integrated into CMR workflow easily, which may simplify research applications involving the quantification of myocardial fibrosis.

Molecular and imaging techniques for bacterial biofilms in joint arthroplasty infections.

Biofilm formation on surfaces is an ancient and integral strategy for bacterial survival. Billions of years of adaptation provide microbes with the ability to colonize any surface, including those used in orthopaedic surgery. Although remarkable progress has been made in the treatment of orthopaedic diseases with implanted prostheses, infection rates remain between 1% and 2%, and are higher for revision surgeries. The chronic nature of implant infections, their nonresponsiveness to antibiotics, and their frequent culture negativity can be explained by the biofilm paradigm of infectious disease. However, the role of biofilms in orthopaedic implant infections and aseptic loosening is controversial. To address these issues, we developed molecular diagnostic and confocal imaging techniques to identify and characterize biofilms associated with infected implants. We designed PCR and reverse transcription (RT)-PCR-based assays that can be used to detect bacterial infections associated with culture-negative joint effusions that distinguish between physiologically active Staphylococcus aureus and Staphylococcus epidermidis. Using clinical isolates of Pseudomonas aeruginosa, we constructed a series of reporter strains expressing colored fluorescent proteins to observe biofilms growing on 316L stainless steel and titanium orthopaedic screws. Three-dimensional structures of Pseudomonas aeruginosa and staphylococci biofilms growing on the screws were documented using confocal microscopy. The application of these tools for clinical diagnosis and biofilm research in animal and in vitro models is discussed.