Osimertinib-induced biventricular cardiomyopathy with abnormal cardiac MRI findings: a case report.

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) inhibitor that is currently the first-line treatment for metastatic EGFR-mutated non-small-cell lung cancer (NSCLC) due to its favorable efficacy and tolerability profile compared to previous generations of EGFR inhibitors. However, it can cause uncommon, yet serious, cardiovascular adverse effects. CASE PRESENTATION: We present the case of a 63-year-old man with EGFR-mutated NSCLC treated with osimertinib who developed new-onset non-ischemic cardiomyopathy with biventricular dysfunction and heart failure in the context of an enlarging pericardial effusion. For the first time, we demonstrate cardiac MR imaging findings associated with osimertinib-associated cardiomyopathy, including focal late gadolinium enhancement and myocardial edema. The patient's biventricular function normalized after initiation of goal-directed medical therapy for heart failure and holding osimertinib. The patient was subsequently started on afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), without recurrence of cardiomyopathy. CONCLUSIONS: This case highlights the need to better understand osimertinib-induced cardiotoxicity and strategies to optimize oncologic care in patients who develop severe cardiac toxicities from cancer therapy. It further underlines the importance of specialized multidisciplinary care of cancer patients who develop cardiotoxicities to optimize their oncologic outcomes.

CathAI: fully automated coronary angiography interpretation and stenosis estimation.

Coronary angiography is the primary procedure for diagnosis and management decisions in coronary artery disease (CAD), but ad-hoc visual assessment of angiograms has high variability. Here we report a fully automated approach to interpret angiographic coronary artery stenosis from standard coronary angiograms. Using 13,843 angiographic studies from 11,972 adult patients at University of California, San Francisco (UCSF), between April 1, 2008 and December 31, 2019, we train neural networks to accomplish four sequential necessary tasks for automatic coronary artery stenosis localization and estimation. Algorithms are internally validated against criterion-standard labels for each task in hold-out test datasets. Algorithms are then externally validated in real-world angiograms from the University of Ottawa Heart Institute (UOHI) and also retrained using quantitative coronary angiography (QCA) data from the Montreal Heart Institute (MHI) core lab. The CathAI system achieves state-of-the-art performance across all tasks on unselected, real-world angiograms. Positive predictive value, sensitivity and F1 score are all ≥90% to identify projection angle and ≥93% for left/right coronary artery angiogram detection. To predict obstructive CAD stenosis (≥70%), CathAI exhibits an AUC of 0.862 (95% CI: 0.843-0.880). In UOHI external validation, CathAI achieves AUC 0.869 (95% CI: 0.830-0.907) to predict obstructive CAD. In the MHI QCA dataset, CathAI achieves an AUC of 0.775 (95%. CI: 0.594-0.955) after retraining. In conclusion, multiple purpose-built neural networks can function in sequence to accomplish automated analysis of real-world angiograms, which could increase standardization and reproducibility in angiographic coronary stenosis assessment.

Intracoronary Imaging and Physiology to Guide PCI: Are We Ready for a Class I Guideline Recommendation?

PURPOSE OF REVIEW: Over the last decade, there has been a plethora of evidence to support the utilization of intravascular coronary imaging and physiological assessment to guide percutaneous coronary interventions (PCI). While there is a class I recommendation for the use of coronary physiology to guide PCI, the use of intravascular coronary imaging remains a class IIa recommendation. Herein, we aimed to review the recent scientific evidence from major trials highlighting the consideration for a future class I guideline recommendation for the use of intracoronary imaging. RECENT FINDINGS: The benefits of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) to guide and optimize PCI have been demonstrated in several large trials. These trials have demonstrated that IVUS reduces major adverse cardiovascular events. Similarly, intracoronary physiology has been demonstrated to be an important tool to guide revascularization decision-making and been associated with a lower incidence of death, non-fatal myocardial infarction, and repeat revascularization compared with angiography alone. With existing clinical outcomes data on the benefit of intracoronary physiology and imaging-guided PCI as well as forthcoming data from ongoing trials regarding the use of these modalities, the interventional cardiology community is bound to transition from routine PCI to precision-, image-, and physiology-guided PCI.

Acute coronary syndrome in patients with hemophilia: a delicate balancing act.

Therapeutic advances have resulted in increased life expectancy in patients with hemophilia. Consequently, the prevalence of coronary artery disease in this population is increasing. Little is known about the optimal management of acute coronary syndrome in these patients. Current guidelines for the management of this condition are based mainly on expert opinion and generally recommend administration of the clotting factor prior to the anticoagulant, antiplatelet, and interventional therapies. We report a case that illustrates the potential harm that may come from this approach: evolution of non-ST-segment elevation acute coronary syndrome into ST-elevation acute coronary syndrome during the administration of recombinant clotting factor. We review available literature and describe the refined informatics-based guidelines for managing acute coronary syndrome in patients with hemophilia we developed in response to the presented clinical case. We propose adopting this novel informatics-based approach, which aids in the identification and early treatment of these patients, operationalizes timely involvement of hematology experts, and gathers data for further study.

Outcomes of primary percutaneous coronary intervention in acute myocardial infarction due to unprotected left main thrombosis: The Asia-Pacific Left Main ST-Elevation Registry (ASTER).

INTRODUCTION: Prior studies of ULM STEMI have been confined to small cohorts. Recent registry data with larger patient cohorts have shown contrasting results. We aim to study the outcomes of patients with unprotected left main (ULM) ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: The Asia-pacific left main ST-Elevation Registry (ASTER) is a multicenter retrospective registry involving 4 sites in Singapore, South Korea, and the United States. The registry included patients presenting with STEMI due to an ULM coronary artery culprit lesion who underwent emergency PCI. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events. RESULTS: A total of 67 patients (mean age 64.2 ± 12.8 years, 53 [79.1%] males) were included. The distal left main bifurcation was most commonly involved (85%, n = 57). Fifty one (76%) patients had TIMI 3 flow post-PCI. The in-hospital mortality rate was 47.8% (n = 32); 61% (n = 41) had cardiac failure, 4% (n = 3) had emergency coronary artery bypass grafting, 1% (n = 1) had a re-infarction, 3% (n = 2) had stroke and 55% (n = 37) had malignant ventricular arrhythmias. On multivariate analysis, predictors of in-hospital mortality included older age (odds ratio (OR) 1.085 (95% confidence interval (CI) 1.002-1.175), P = 0.044), diabetes mellitus (OR 10.882 (95%CI 11.074-110.287), P = 0.043) and absence of post-PCI TIMI 3 flow (OR 71.429 (95%CI 2.985-1000), P = 0.008). CONCLUSIONS: STEMI from culprit unprotected left main coronary artery stenosis is associated with significant mortality and morbidity. Emergency PCI provides an important treatment option in this high-risk group, but in-hospital mortality remains high.

Long-term outcomes of angiographically confirmed coronary stent thrombosis: results from a multicentre California registry.

AIMS: Limited data exist on long-term outcomes of patients with stent thrombosis (ST). Our aim was to describe the long-term outcomes after angiographically confirmed ST. METHODS AND RESULTS: In this multicentre registry, consecutive cases of definite ST were identified between 2005 and 2013. Clinical and procedural characteristics, in-hospital outcomes and long-term survival up to five years were compared between those with and those without adverse cardiovascular and cerebrovascular events (MACCE), defined as all-cause mortality, myocardial infarction and stroke. Two hundred and twenty-one patients with 239 stent thrombosis events were identified. Patients who developed MACCE were older, less likely to be men, and less likely to have hypertension. Angiographic characteristics were similar. Patients who had a MACCE event showed a trend towards a lower likelihood of procedural success (86% vs. 91%, p=0.05). MACCE rates were 22% at one year and 41% at five years. All-cause mortality was 13% at one year and 24% at five years. On multivariable analysis, age, diabetes mellitus, active smoking and ST at a bifurcation were independently associated with the occurrence of MACCE up to five years. CONCLUSIONS: Age, active smoking, diabetes mellitus and bifurcation disease are independently associated with long-term MACCE over a five-year follow-up period.

"Not so fast!" the complexity of attempting to decrease door-to-floor time for emergency department admissions.

BACKGROUND: Successful quality improvement is fundamental to high-performing health care systems, but becomes increasingly difficult as systems become more complex. Previous attempts at the University of California, San Francisco (UCSF) Medical Center to reduce door-to-floor (D2F) time -the time required to move an ill patient through the emergency department (ED) to an appropriate inpatient bed-had not resulted in meaningful improvement. An analysis of why attempts at decreasing D2F times in the ED had failed, with attention to contextual factors, yields recommendations on how to decrease D2F time. METHODS: A team of 11 internal medicine residents, in partnership with the Patient Flow Executive Steering Committee, performed a literature review, process mapping, and analysis of the admissions process. The team conducted interviews with medical center staff across disciplines, members of high-performing patient care units, and leaders of peer institutions who had undertaken similar efforts. FINDINGS AND RECOMMENDATIONS: Each of the following three domains-(1) Improving Work Flow, (2) Changing Culture, and (3) Understanding Incentives-is independently an important source of resistance and opportunity. However, the improvement work and understanding of complexity science suggest that all three domains must be addressed simultaneously to effect meaningful change. Recommendations include eliminating redundant and frustrating processes; encouraging multidisciplinary collaboration; fostering trust between departments; providing feedback on individual performance; enhancing provider buy-in; and, ultimately, uniting staff behind a common goal. CONCLUSION: By conceptualizing the hospital as a complex adaptive system, multiple interrelated groups can be encouraged to work together and accomplish a common goal.

Developing entrustable professional activities as the basis for assessment of competence in an internal medicine residency: a feasibility study.

BACKGROUND: Graduate medical education programs assess trainees' performance to determine readiness for unsupervised practice. Entrustable professional activities (EPAs) are a novel approach for assessing performance of core professional tasks. AIM: To describe a pilot and feasibility evaluation of two EPAs for competency-based assessment in internal medicine (IM) residency. SETTING/PARTICIPANTS: Post-graduate year-1 interns (PGY-1s) and attendings at a large internal medicine (IM) residency program. PROGRAM DESCRIPTION: Two Entrustable professional activities (EPA) assessments (Discharge, Family Meeting) were piloted. PROGRAM FEASIBILITY EVALUATION: Twenty-eight out of 43 (65.1 %) PGY-1 s and 32/43 (74.4 %) attendings completed surveys about the Discharge EPA experience. Most who completed the EPA assessment (10/12, 83.8 %, PGY-1s; 9/11, 83.3 %, attendings) agreed it facilitated useful feedback discussions. For the Family Meeting EPA, 16/26 (61.5 %) PGY-1s completed surveys, and most who participated (9/12 PGY1s, 75 %) reported it improved attention to family meeting education, although only half recommended continuing the EPA assessment. DISCUSSION: From piloting two EPA assessments in a large IM residency, we recognized our reminder systems and time dedicated for completing EPA requirements as inadequate. Collaboration around patient safety and palliative care with relevant clinical services has enhanced implementation and buy-in. We will evaluate how well EPA-based assessment serves the intended purpose of capturing trainees' trustworthiness to conduct activities unsupervised.

The value in the evidence: teaching residents to "choose wisely".

The Accreditation Council for Graduate Medical Education mandates that training physicians "incorporate considerations of cost awareness" into practice. However, medical education has traditionally avoided addressing costs, and most residency programs currently lack curricula to fulfill this requirement. With the recent widespread emphasis on unsustainable costs, inefficiencies, and waste in healthcare, the need to appropriately train physicians in this domain is increasingly apparent. In this article, we describe the implementation of a resident-led, case-based cost awareness curriculum for medicine residents at the University of California, San Francisco, sharing our keys to success and defining guiding principles.

Identifying entrustable professional activities in internal medicine training.

BACKGROUND: Entrustable professional activities (EPAs) can form the foundation of competency-based assessment in medical training, focused on performance of discipline-specific core clinical activities. OBJECTIVE: To identify EPAs for the Internal Medicine (IM) Educational Milestones to operationalize competency-based assessment of residents using EPAs. METHODS: We used a modified Delphi approach to conduct a 2-step cross-sectional survey of IM educators at a 3-hospital IM residency program; residents also completed a survey. Participants rated the importance and appropriate year of training to reach competence for 30 proposed IM EPAs. Content validity indices identified essential EPAs. We conducted independent sample t tests to determine IM educator-resident agreement and calculated effect sizes. Finally, we determined the effect of different physician roles on ratings. RESULTS: Thirty-six IM educators participated; 22 completed both surveys. Twelve residents participated. Seventeen EPAs had a content validity index of 100%; 10 additional EPAs exceeded 80%. Educators and residents rated the importance of 27 of 30 EPAs similarly. Residents felt that 10 EPAs could be met at least 1 year earlier than educators had specified. CONCLUSIONS: Internal medicine educators had a stable opinion of EPAs developed through this study, and residents generally agreed. Using this approach, programs could identify EPAs for resident evaluation, building on the initial list created via our study.

Who's underworked and who's overworked now? An update on radiologist shortage and surplus.

OBJECTIVE: The purpose of this study was to present an updated report on the radiologist surplus and shortage situation using a recently developed improved measure-namely, the extent to which radiologists desire less or more work if their income were to change by the same percentage as their workload. MATERIALS AND METHODS: Non-individually identifiable data from the American College of Radiology's (ACR's) 2007 Survey of Diagnostic Radiologists were used. Responses were weighted to be representative of all posttraining professionally active radiologists in the United States. Information is presented for all radiologists and according to such factors as type and size of practice, radiologist subspecialty, and geographic region. Multivariable regression analysis was used to identify the probable causal links between desired workload change and characteristics of radiologists and the practices where they work. Comparisons were made with ACR's similar 2003 Survey of Radiologists. RESULTS: The net average workload change sought in 2007 was an approximately 3% increase. In 2003, radiologists on average did not desire a statistically significant change in workload. Regression analysis for 2007 showed a pattern of relative shortages and surpluses that was generally, but not entirely, different from that found in 2003. CONCLUSION: The overall balance between the demand and the supply of radiologists shifted toward a surplus between 2003 and 2007. According to our measure, we judge there was a close balance in 2003, but a 3% surplus in 2007. The employment market seems generally, but not universally, to self-correct relative shortages and surpluses in individual geographic areas and subspecialties within a few years.