Outcomes of Functional Testing Versus Invasive Cardiac Catheterization for the Evaluation of Intermediate Severity Coronary Stenosis Detected on Cardiac Computed Tomography Angiography.

INTRODUCTION: The aim of this study was to evaluate the effectiveness of functional testing in comparison to invasive coronary angiography (ICA) among acute chest pain patients whose first diagnostic modality was a coronary computed tomography angiogram (CCTA) and were found to have intermediate coronary stenosis, defined as 50%-70% luminal stenosis. METHODS: We conducted a retrospective review of 4763 acute chest pain patients ≥18 years old who received a CCTA as the initial diagnostic modality. Of these, 118 patients met enrollment criteria and proceeded to either stress test (80/118) or directly to ICA (38/118). The primary outcome was 30-day major adverse cardiac event, consisting of acute myocardial infarction, urgent revascularization, or death. RESULTS: There was no difference in 30-day major adverse cardiac event among patients who underwent initial stress testing versus directly referred to ICA (0% vs. 2.6%, P = 0.322) following CCTA. The rate of revascularization without acute myocardial infarction was significantly higher among those who underwent ICA versus stress test [36.8% vs. 3.8%, P < 0.0001; adjusted odds ratio: 9.6, 95% confidence interval, 1.8-49.6]. Patients who underwent ICA had a higher rate of catheterization without revascularization within 30 days of the index admission in comparison to those who underwent initial stress testing (55.3% vs. 12.5%, P < 0.0001; adjusted odds ratio: 26.7, 95% confidence interval, 6.6-109.5). CONCLUSION: Among patients with intermediate coronary stenosis on CCTA, a functional stress test compared with ICA may prevent unnecessary revascularization and improve cardiac catheterization yield without negatively affecting the 30-day patient safety profile.

Validation of Appropriate Use Criteria for Coronary Computed Tomographic Angiography for Chest Pain Evaluation in a Tertiary Care Emergency Room.

PURPOSE: Appropriate use criteria (AUC) defines the appropriateness of imaging procedures for specific clinical scenarios to promote evidence-based utilization and improve cost-effective care. The goal of this study was to assess the diagnostic yield and downstream health care resource utilization according to the AUC categorization for coronary computed tomography angiography (CCTA) in emergency department (ED) patients presenting with chest pain. MATERIALS AND METHODS: A total of 789 consecutive patients in the ED with chest pain and no known coronary artery disease (CAD) who underwent CCTA were classified as appropriate, uncertain, or inappropriate use according to the 2010 AUC. We abstracted index and 30-day data from the electronic medical record to determine diagnostic yield (rate of obstructive CAD and revascularization) and health care resource utilization (downstream stress test and 30-d hospital return rate). RESULTS: Rates of appropriate, uncertain, and inappropriate utilization were 48.4%, 48.8%, and 2.8%. Among appropriate, uncertain, and inappropriate classifications, rates of obstructive CAD were 9%, 8%, and 32% (P=0.002); rates of revascularization were 3%, 1%, and 36% (P<0.001); downstream stress test utilization rates were 5% versus 5% versus 14% (P=0.17), and 30-day hospital return rates were 6% versus 6% versus 5% (P>0.99), respectively. CONCLUSIONS: Appropriate and uncertain uses were associated with low diagnostic yield compared with inappropriate use; however, our findings do not demonstrate differences between appropriate use categories with respect to downstream health care resource utilization. Further studies are needed to define the role of AUC for CCTA in the ED setting.

Outcomes of a Resident-Led Early Hospital Discharge Intervention.

BACKGROUND: Early morning patient discharge from the hospital is increasingly being recognized as a key dimension of quality of care. At our institution, there is a significantly lower early discharge rate on the teaching hospitalist teams in comparison with the non-teaching teams. OBJECTIVE: To implement a resident-driven intervention in the teaching medical services to increase overall discharge order rate before 11 am (DOB-11) and assess the effect of this intervention on hospital length of stay (LOS), 30-day readmission rates (RR), and resident perception. DESIGN: Interrupted time series as well as controlled before-after designs. PARTICIPANTS: All inpatients discharged from general medicine units. INTERVENTIONS: We implemented an educational didactic in conjunction with resident-attending daily walk rounds followed by resident-led multidisciplinary discharge huddles to identify next-day discharges. MAIN MEASURES: The primary outcome was DOB-11 rates 18 months pre- and 12 months post-intervention. SECONDARY OUTCOMES: LOS and RR. Additionally, we assessed residents' perception of the early discharge protocol. KEY RESULTS: The DOB-11 rate increased from 12 to 29% (p < 0.001), LOS increased by 1.47 days (P < 0.001), and RR increased by 0.32% (P = 0.84), respectively, on the teaching teams. Compared with the non-teaching (control) teams, the teaching teams registered a greater increase in DOB-11 rate (by 17%, p < 0.001; ratio of adjusted ORs 2.16; 95% CI, 1.65, 2.85; p value < 0.001), small increase in LOS (by 0.74 day, p = 0.39; ratio of adjusted post-/pre-intervention ratio [teaching] and post-/pre- intervention ratio [non-teaching] = 1.05, 95% CI, 0.97, 1.14, p = 0.23), and relative increase in RR (by 3.98%, p = 0.07, and ratio of ORs = 1.35, 95% CI, 1.03, 1.8), p = 0.03). Approximately 55% (16/29) of the residents agreed that the early discharge initiative helped in understanding the importance of prioritizing patients for early discharge. Additionally, 55% (20/36) of the residents "agreed" that the early discharge initiative compromised their learning during teaching rounds. CONCLUSION: Our study demonstrates that DOB-11 is an achievable goal, not only for non-teaching teams but also for resident-run teaching teams.

Comparing the Modified History, Electrocardiogram, Age, Risk Factors, and Troponin Score and Coronary Artery Disease Consortium Model for Predicting Obstructive Coronary Artery Disease and Cardiovascular Events in Patients With Acute Chest Pain.

The objective of this study was to compare the History, Electrocardiogram, Age, Risk factors, and Troponin (HEART) score and clinical coronary artery disease (CAD) consortium (CADC) model for predicting obstructive CAD (≥50% stenosis on coronary computed tomographic angiography) and 30-day major adverse cardiovascular events (MACE, composite of acute myocardial infarction, revascularization, and mortality). We studied 1981 patients with no known CAD who presented with acute chest pain and had negative initial troponin and electrocardiogram. Chest pain was classified as typical, atypical, and nonanginal and used to score the history component of the modified HEART score. The C-statistic for predicting obstructive CAD was 0.747 [95% confidence interval (CI), 0.712-0.783] for the HEART score and 0.792 (95% CI, 0.762-0.823) for the CADC model (P = 0.0005). The C-statistic for predicting 30-day MACE was 0.820 (95% CI, 0.774-0.864) for the HEART score and 0.850 (95% CI, 0.800-0.891) for the CADC model (P = 0.11). Among the 48.3% of patients for whom the CADC model predicted ≤5% probability of obstructive CAD, the observed 30-day MACE was 0.6%; among the 48.9% of patients for whom the HEART score was ≤2, the 30-day MACE was 0.6%. In conclusion, the CADC model was more effective at predicting obstructive CAD compared to the HEART score. The HEART score and CADC model were equally effective to safely identify low-risk patients by achieving <1% missed 30-day MACE.

Lactic Acid Is an Independent Predictor of Mortality and Improves the Predictive Value of Existing Risk Scores in Patients Presenting With Acute Gastrointestinal Bleeding.

BACKGROUND: There are validated clinical risk scores for risk stratifying patients presenting with acute upper gastrointestinal bleed (GIB), including Glasgow-Blatchford score (GBS), Pre-endoscopic Rockall score (RS-PE) and post-endoscopic complete Rockall Score (RS-C), and AIMS65. Several studies have explored the predictive value of lactic acid (LA) in the context of GI bleeding, but the prognostic role of LA and its incremental value in combination with existing clinical risk scores is not well defined. METHODS: We conducted a retrospective analysis of consecutive patients presenting to the emergency department of a single large academic tertiary care center from January 2014 to December 2015 with a charted diagnosis of acute GIB, inclusive of both upper and lower sources. We evaluated the independent role of LA as well as three clinical risk scores for predicting in-hospital mortality in these patients. RESULTS: Out of 704 patients admitted with acute GI bleeding, 366 patients had LA measured on presentation to the emergency department. The mean LA level, GBS, RS-PE and RS-C were found to be significantly higher in non-survivors, while there was no difference in the mean AIMS65 score between survivors and non-survivors. A multivariate logistic regression analysis showed that LA level was an independent predictor of in-hospital mortality. The area under the curve (AUC) for the receiver operator characteristic for RS-C, RS-PE, and GBS were 0.742, 0.675, and 0.652, respectively. When integrating LA into the above risk scores, the AUC for RS-C, RS-PE, and GBS showed statistical significance improvements to 0.780 (P = 0.04), 0.774 (P = 0.012), and 0.706 (P = 003), respectively. CONCLUSIONS: In unselected patients with GIB who presented to the emergency department, LA is an independent predictor of in-hospital mortality. Integration of LA into RS-C, RS-PE, and GBS risk scores improved their ability to predict in-hospital mortality. The modified LA-based RS-PE (L-Rockall pre-endoscopic) score demonstrated predictive value comparable to the post-endoscopic RS-C.

Diagnostic and Prognostic Role of the Modified Diamond-Forrester Model in Combination With Coronary Calcium Score in Acute Chest Pain Patients.

BACKGROUND: The aim of this study was to evaluate whether pretest probability (PTP) assessment using the Diamond-Forrester Model (DFM) combined with coronary calcium scoring (CCS) can safely rule out obstructive coronary artery disease (CAD) and 30-day major adverse cardiovascular events (MACE) in acute chest pain patients. METHODS: We retrospectively evaluated consecutive patients, age ≥18 years, with no known CAD, negative initial electrocardiogram, and troponin level. All patients had coronary computed tomographic angiography (CCTA) with CCS, and our final cohort consisted of 1988 patients. Obstructive CAD was defined as luminal narrowing of ≥50% in 1 or more vessels by CCTA. Patients were classified according to PTP as low (<10%), intermediate (10%-90%), or high (>90%). RESULTS: The DFM classified 293 (14.7%), 1445 (72.7%), and 250 (12.6%) of patients as low, intermediate, and high risk, respectively, with corresponding 30-day MACE rates of 0.0%, 2.35%, and 14.8%. For patients with intermediate PTP and CCS ≤10, the negative predictive value was 99.2% (95% confidence interval: 98.7-99.8) for 30-day MACE while it was 92.62% (95% confidence interval: 87.9-97.3) for patients with high PTP. Among patients with a high PTP and CCS of zero, the prevalence of 30-day MACE and obstructive CAD remained high (7.07% and 10.1%, respectively). CONCLUSIONS: In acute chest pain patients without evidence of ischemia on initial electrocardiogram and cardiac troponin, low PTP by DFM or the combination of intermediate PTP and CCS ≤10 had excellent negative predictive values to rule out 30-day MACE. CCS is not sufficient to exclude obstructive CAD and 30-day MACE in patients with high PTP.

Mid-Left Ventricular Ballooning Variant Takotsubo Syndrome Induced by Treadmill Exercise Stress Testing.

Stress-induced cardiomyopathy, also known as takotsubo cardiomyopathy, presents similar to a myocardial infarction after a physical or emotional stressor but without any evidence of obstructive coronary artery disease. Different patterns of myocardial involvement and several triggering events have been reported, but classically this condition is characterized by a stress-induced transient left ventricular apical systolic dysfunction. We describe a case of treadmill exercise stress testing-triggered variant of takotsubo cardiomyopathy with mid-left ventricular hypokinesis.

Validity of Coronary Artery Disease Consortium Models for Predicting Obstructive Coronary Artery Disease & Cardiovascular Events in Patients with Acute Chest Pain Considered for Coronary Computed Tomographic Angiography.

Although the majority of acute chest pain patients are diagnosed with noncardiac chest pain after noninvasive testing, identifying these low-risk patients before testing is challenging. The objective of this study was to validate the coronary artery disease (CAD) consortium models for predicting obstructive CAD and 30-day major adverse cardiovascular events (MACE) in acute chest pain patients considered for coronary computed tomography angiogram, as well as to determine the pretest probability threshold that identifies low-risk patients with <1% MACE. We studied 1,981 patients with no known CAD and negative initial troponin and electrocardiogram. We evaluated CAD consortium models (basic: age, sex, and chest pain type; clinical: basic + diabetes, hypertension, dyslipidemia, and smoking; and clinical + coronary calcium score [CAC] models) for prediction of obstructive CAD (≥50% stenosis on coronary CT angiogram) and 30-day MACE (Acute Myocardial Infarction, revascularization, and mortality). The C-statistic for predicting obstructive CAD was 0.77 (95% confidence interval [CI] 0.73 to 0.77) for the basic, 0.80 (95% CI 0.77 to 0.80) for the clinical, and 0.88 (95% CI 0.85 to 0.88) for the clinical + CAC models. The C-statistic for predicting 30-day MACE was 0.82 (95% CI 0.77 to 0.87) for the basic, 0.84 (95% CI 0.79 to 0.88) for the clinical, and 0.87 (95% CI 0.83 to 0.91) for the clinical + CAC models. In 47.3% of patients for whom the clinical model predicted ≤5% probability for obstructive CAD, the observed 30-day MACE was 0.53% (95% CI 0.07% to 0.999%); in the 66.9% of patients for whom the clinical + CAC model predicted ≤5% probability, the 30-day MACE was 0.75% (95% CI 0.29% to 1.22%). We propose a chest pain evaluation algorithm based on these models that classify 63.3% of patients as low risk with 0.56% (95% CI 0.15% to 0.97%) 30-day MACE. In conclusion, CAD consortium models have excellent diagnostic and prognostic value for acute chest pain patients and can safely identify a significant proportion of low-risk patients by achieving <1% missed 30-day MACE.

Worsening Hypoxemia in the Face of Increasing PEEP: A Case of Large Pulmonary Embolism in the Setting of Intracardiac Shunt.

BACKGROUND Patent foramen ovale (PFO) are common, normally resulting in a left-to-right shunt or no net shunting. Pulmonary embolism (PE) can cause sustained increased pulmonary vascular resistance (PVR) and right atrial pressure. Increasing positive end-expiratory pressure (PEEP) improves oxygenation at the expense of increasing intrathoracic pressures (ITP). Airway pressure release ventilation (APRV) decreases shunt fraction, improves ventilation/perfusion (V/Q) matching, increases cardiac output, and decreases right atrial pressure by facilitating low airway pressure. CASE REPORT A 40-year-old man presented with dyspnea and hemoptysis. Oxygen saturation (SaO2) 80% on room air with A-a gradient of 633 mmHg. Post-intubation SaO2 dropped to 71% on assist control, FiO2 100%, and PEEP of 5 cmH20. Successive PEEP dropped SaO2 to 60-70% and blood pressure plummeted. APRV was initaiated with improvement in SaO2 to 95% and improvement in blood pressure. Hemiparesis developed and CT head showed infarction. CT pulmonary angiogram found a large pulmonary embolism. Transthoracic echocardiogram detected right-to left intracardiac shunt, with large PFO. CONCLUSIONS There should be suspicion for a PFO when severe hypoxemia paradoxically worsens in response to increasing airway pressures. Concomitant venous and arterial thromboemboli should prompt evaluation for intra-cardiac shunt. Patients with PFO and hypoxemia should be evaluated for causes of sustained right-to-left pressure gradient, such as PE. Management should aim to decrease PVR and optimize V/Q matching by treating the inciting incident (e.g., thrombolytics in PE) and by minimizing ITP. APRV can minimize PVR and maximize V/Q ratios and should be considered in treating patients similar to the one whose case is presented here.

Cell culture-based analysis of postsynaptic membrane assembly in muscle cells.

We report a method for studying postsynaptic membrane assembly utilizing the replating of aneural cultures of differentiated skeletal muscle cells onto laminin-coated surfaces. A significant limitation to the current cell culturebased approaches has been their inability to recapitulate the multistage surface acetylcholine receptor (AChR) redistribution events that produce complex AChR clusters found at the intact neuromuscular junction (NMJ). By taking advantage of the ability of substrate laminin to induce advanced maturation of AChR aggregates on the surface of myotubes, we have developed a secondary-plating method that allows more precise analysis of the signaling events connecting substrate laminin stimulation to complex AChR cluster formation. We validate the utility of this method for biochemical and microscopy studies by demonstrating the roles of RhoGTPases in substrate laminin-induced complex cluster assembly.

Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways.

During neuromuscular junction formation, extracellular matrix-mediated signals cause muscle surface acetylcholine receptors (AChRs) to aggregate at synaptic sites. Two extracellular matrix proteins, agrin and laminin, have each been shown to initiate signaling pathways that culminate in AChR clustering in cultured muscle cells. Here we present evidence that laminin-induced AChR clustering is mediated by the activation of the Rho GTPases Cdc42, Rac and Rho. Clustering in response to laminin is blocked by the dominant negative mutants Cdc42N17, RacN17 and RhoN19, as well as by the Rho inhibitor C3 transferase. Moreover, laminin-induced AChR clustering is impaired by the Rho kinase inhibitor Y-27632. Agrin-induced AChR clustering has previously been shown to require activation of Cdc42, Rac and Rho. Therefore, although agrin and laminin use distinct transmembrane receptors to initiate AChR clustering, their signaling pathways converge at the level of Rho GTPase activation.

Cooperative regulation by Rac and Rho of agrin-induced acetylcholine receptor clustering in muscle cells.

A key aspect of neuromuscular synapse formation is the clustering of muscle acetylcholine receptors (AChR) at synaptic sites in response to neurally secreted agrin. Agrin-induced AChR clustering in cultured myotubes proceeds via the initial formation of small microclusters, which then aggregate to form AChR clusters. Here we show that the coupling of agrin signaling to AChR clustering is dependent on the coordinated activities of Rac and Rho GTPases. The addition of agrin induces the sequential activation of Rac and Rho in C2 muscle cells. The activation of Rac is rapid and transient and constitutes a prerequisite for the subsequent activation of Rho. This temporal pattern of agrin-induced Rac and Rho activation reflects their respective roles in AChR cluster formation. Whereas agrin-induced activation of Rac is necessary for the initial phase of AChR cluster formation, which involves the aggregation of diffuse AChR into microclusters, Rho activation is crucial for the subsequent condensation of these microclusters into full-size AChR clusters. Co-expression of constitutively active forms of Rac and Rho is sufficient to induce the formation of mature AChR clusters in the absence of agrin. These results establish that Rac and Rho play distinct but complementary roles in the mechanism of agrin-induced AChR clustering.