Chu Review: Zhang 2023’s neutrophil to lymphocyte ratio to screen for aortic syndrome

Zhang, et al. 2023. Comparisons of potential values of D-dimer and the neutrophil- to-lymphocyte ratio in patients with suspected acute aortic syndrome. AJEM, 69, p44-51.
https://www.sciencedirect.com/science/article/pii/S0735675723001742

One Liner: The neutrophil-to-lymphocyte ratio (NLR) shows some promise for diagnosis of aortic syndromes, but needs further study; will not change my practice

Brief Summary:

• Aortic syndromes are notoriously difficult to diagnosis, nonspecific, and have high mortality as well as uncertain incidence in the population, requiring timely diagnostic modalities.
• D Dimer is currently used as a nonspecific screen for aortic syndromes; the study authors wished to evaluate it NLR could also be used as a screening test.
• Single center retrospective chart analysis in China including pts suspected to have aortic syndrome, but had unclear exclusion criteria (including “some” hematologic and malignant diseases).
• Authors claim NLR had comparable screening utility to D Dimer, though study authors claim that diagnosis of aortic syndrome could also be made by CXR, ECG, and clinical suspicion, as opposed to the current United States standard of radiologic aortic visualization (e.g. ultrasound, angiogram), and study authors did not elaborate on what modalities were used specifically, how frequently, and what interventions (e.g. medical optimization, surgery, palliation) were used for these pts.
• Main limitations include unclear communication by study authors and ease of generalization to other hospitals and systems. Furthermore, outcomes are not defined as primary, secondary, etc., and statistical analysis, power, etc. suffers from skipping such an early step. Authors do have a good number of patients, but their ability to communicate their findings is unclear.
• Will not change my practice until I see a better written paper and generalization to other facilities.

Chu Review: Landon 2023’s differences in tx & outcomes of MI based on SES

Landon, et al. 2023. Differences in Treatment Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients in 6 Countries. JAMA Cardiology, 329, 13, p 1088-1097.
https://jamanetwork.com/journals/jama/fullarticle/2803045

One Liner: It is of no surprise that lower income patients that low income pts have worse outcomes and worse access to care in many conditions, specifically in this case STEMI and NSTEMI; will not change my practice

Brief Summary:

• Clinical Question: Are patients that are older and low-income, compared to patients that are high-income, having worse outcomes in acute myocardial infarction, as measured by [primary] 30-d and 1-yr mortality and [secondary] rates of hospital length of stay, 30 d readmission, and is there an income disparity in use of cardiac cath, PCI, CABG during initial hospitalization and within 90 d of admission?
• This study looked at a compilation of data from 6 countries (US, Canada, England, Netherlands, Israel, Taiwan) and specifically used STEMI due to internationally agreed diagnostic criteria.
• The pts used zip code income averages as a proxy to define if a pt had High or Low Income and looked at the top 20% as “High” and bottom 20% as “Low” income.
• The primary outcome (30 d and 1 yr mortality) was worse in low income pts.
• The secondary outcomes (revascularization by cath, PCI, CABG; hospital LOS; readmission within 30 d) were also worse in low income pts.
• Some limitations, like lack of race & ethnicity data (which can inform social determinants of health), lack of discharge disposition (i.e. to SNF, home, which insurance can influence), and also readmissions being “defined” by the primary diagnosis listed for readmission (which some hospitals will unethically change to avoid legislative punishments).

Chu Review: Bracey 2023’s FOCUS for FWMA in ACS

Bracey, et al. 2023. FOCUS may detect wall motion abnormalities in patients with ACS, A retrospective study. AJEM, 69, p17-22.
https://www.sciencedirect.com/science/article/pii/S0735675723001717

One Liner: Focused cardiac ultrasound (FOCUS) is a useful tool in the ED and can be competently performed by ED physicians at all levels of training for detection of regional WMA; will not change my practice since I have a low threshold to perform FOCUS, but can be very encouraging for those who might not regularly do so.

Brief Summary:

• Clinical Question: In patients presenting to the ER with symptoms worrisome for ACS, is focused cardiac ultrasound (FOCUS) performed in the ER beneficial, as measured by the outcomes of [primary] sensitivity, specificity, and accuracy in detecting regional wall motional abnormality (RWMA), and [secondary] sensitivity of FOCUS compared to formal echo to detect WMA in cath proven OMI; sensitivity of ER FOCUS compared to formal echo for detection of WMA in pts without OMI; the sensitivity and specificity of FOCUS based on level of training.
• The ED physician is primarily looking for life threatening causes of chest pain, especially ACS given that treatment requires timely recognition and expedited transport to specialized care, e.g. the cath lab.
• Primary and secondary outcomes at this single academic tertiary care center showed promising results in sensitivity, specificity, and accuracy at all levels of ED physician training, however notable limitations incl relatively low sample size, social conditions of the hospital location (affluent Caucasian part of the country), and early termination of pt recruitment due to the covid-19 pandemic.
• Overall will not change my practice since I have a low threshold to do a FOCUS in the ER anyways, but there is much to be done before such a thing is accepted as standard of care. Might be reassuring to encourage more people to do FOCUS, especially as the presence of regional WMA can be very concerning in pts who are at high risk of ACS (though of course, the absence of WMA does not rule out ACS).

Longer Summary

Introduction

• Chest pain is a common chief complaint bringing people to the ER, about 6 million visits/yr.

• Most initial diagnostics, after history and physical, for chest pain include an ECG and may also include other modalities such as chest x-ray, cardiac markers (e.g. troponin, BNP), or others.
• The ER is trying to screen for and find pts with life threatening causes for chest pain, especially ACS which may require reperfusion therapy, e.g. cath vs thrombolytics.
• Many hospitals may never get around to a formal echocardiogram until many hours after initial presentation to the ER, and the STEMI vs non-STEMI on ECG paradigm may miss significant numbers of pts who would benefit from early cardiac catheterization.

Methodology & Patient Info

• Clinical Question: In patients presenting to the ER with symptoms worrisome for ACS, is focused cardiac ultrasound (FOCUS) performed in the ER beneficial, as measured by the outcomes of [primary] sensitivity, specificity, and accuracy in detecting regional wall motional abnormality (RWMA), and [secondary] sensitivity of FOCUS compared to formal echo to detect WMA in cath proven OMI; sensitivity of ER FOCUS compared to formal echo for detection of WMA in pts without OMI; the sensitivity and specificity of FOCUS based on level of training.
• Inclusion: Pts > 17 yo who presented to the ER w suspected ACS from July 1, 2019 to Oct 24, 2020 (early termination due to covid-19 pandemic), who had FOCUS in the ER and formal echo during the index visit.
• Exclusion: None specifically listed other than not meeting the inclusion criteria
• The study took place at a single center academic tertiary hospital from July 2019 to October 2020. Patient recruitment was terminated early due to the covid-19 pandemic. This was a retrospective chart review of pts who essentially had an in-hospital alert system (similar to a Cardiac Alert, STEMI Alert, etc.) activated. Pts tended to be 62 yo, about 65% were male, 76% were Caucasian, and there was a spread of cardiovascular disease and risk factors, including DM (31%), HTN (72%), HLD (57%), smoking (62%), CHF (18%), and CAD (29%).
• 65 pts ultimately met the Inclusion Criteria for this study. Of these 65, 82% had urgent or emergent coronary angiography, of which 71% had OMI at the time of coronary angiogram.

Outcomes

• Primary: Accuracy, sensitivity, and specificity of ED FOCUS compared to formal echo for detection of regional WMA.
• Secondary:
  • Sensitivity of FOCUS vs formal echo for detection of WMA in pts who had cardiac cath proven OMI (occlusion myocardial infarction)
  • Sensitivity of FOCUS vs formal echo in pts without OMI
  • Sensitivity and specificity in FOCUS depending on level of training (resident, ultrasound fellow, attending)

Results & Discussion

• Primary Outcome:
  • POCUS for WMA performed by ED physicians had a sensitivity 94%, specificity 35%, and overall accuracy of 78%.
  • Of note, formal echocardiogram (the comparison for the primary outcome) was performed based on the availability of a technician or cardiology fellow and an attending cardiologist to interpret the imaging. Some echocardiograms in the hospital system of this study were performed after coronary angiogram, which could have led to resolution of WMA’s, either by time or by treatment (such as catheterization, stent placement, bypass, etc.)
• Secondary Outcome:
  • There were 31 residents who had sensitivity 86%, specificity 56%, and accuracy of 77%.
  • There were 34 ultrasound fellows and attending physicians who had sensitivity 85%, specificity 75%, and accuracy of 82%.
• The presence of regional WMA is very useful, but its absence does not necessarily exclude OMI.
• These results may be best for pts who do not have a slam dunk STEMI on ECG, but are still high risk candidates for OMI.
• A benefit to this study was that it was performed by ED physicians still in the ED and reflect actual clinical practice, as opposed to idealized formal echo situations.
• Limitations raised by the authors include early termination due to pandemic, this being a retrospective single center study in a largely affluent Caucasian population, lack of blinding of clinicians to patient information (especially as they themselves may have been doing the FOCUS), timing of the formal echocardiogram.

Chu Review: Ammirati 2023’s review on dx and tx of acute myocarditis

Ammirati, et al. 2023. Diagnosis and treatment of acute myocarditis: a review. JAMA, 329, 13, p 1098-1113.
https://jamanetwork.com/journals/jama/fullarticle/2803039

One Liner: Myocarditis may have a preceding viral syndrome, can present with a variety of symptoms of cardiac EOD, dysrhythmias, ischemia, but almost half can have a negative troponin; should get NSAID and ASA, cardiac support, and be admitted; will not change my practice

Brief Summary

• Most common precipitating cause of a preceding viral infection, rarely from autoimmunity and even more rarely from chemotherapy immune checkpoint inhibitors.
• Infective causes can also include HIV, Dengue, Chagas, Lyme disease.
• Certain genes can lead to higher risk and poorer outcomes.
• Most pts are younger adults, predominantly men. Most common symptoms are chest pain, dyspnea, and fever. About 3-9% of pts present with fulminant cardiogenic shock.
• Initial evaluation typically sees elevated troponin and inflammatory markers. Sending off serology for other diseases such as HIV and Borrelia may be recommended.
• ECG can show ischemic changes, esp inferior and lateral leads; wide QRS, AV blocks, ventricular dysrhythmias are high risk.
• Echo can show thickened myocardium, effusion.
• Coronary CT occasionally used, but the main definitive diagnostic modalities are Cardiac MRI and Biopsy.
• All pts with myocarditis should be hospitalized. Uncomplicated cases typically can be treated with NSAID and ASA for chest pain. Complicated cases (LV dysfunction, acute heart failure, ventricular dysrhythmia, advanced AV block, cardiogenic shock) go to the ICU and may need antidysrhythmic medications, pacemaker, defib, cardioversion, etc.
• Medical treatments based on etiology and may involve removal of offending agents, antimicrobials, immunosuppression, steroids.
• Mechanical and surgical supports like AICD, aortic balloon pumps, VA-ECMO, LVAD, and cardiac transplants may be needed.
• Factors worsening prognosis include cardiogenic shock, giant cell, QRS > 120 ms on initial ECG, requirement of mechanical supports, ventricular dysrhythmias, myocardial fibrosis, genetic disorders, and etiology from giant cell myocarditis or immune checkpoint inhibitor.
• Many pediatric cases have a viral prodrome, and most common symptoms are fatigue, less frequently GI symptoms, dyspnea, and chest pain. The differential also includes vasculidites (e.g. Kawasaki), MIS-C, others. No high quality evidence for treatment in children, IVIG and steroids frequently used.

Chu Review: Redfield 2023’s review on HFpEF

Redfield, et al. 2023. Heart failure with preserved ejection fraction: a review. JAMA, 329, 10, p827-838.
https://jamanetwork.com/journals/jama/fullarticle/2802310

One Liner: HFpEF is a multimodal, multiorganic disease, but in the ER, treat similar to HFrEF unless there are extrenuating circumstances; will not change my practice, but was a nice review

Brief Summary:

• Multi-organ system involvement despite a preserved ejection fraction.
• Dx gold standard is right heart cath but that is not always available.
• Comorbidities often incl pulm disease, anemia, dysrhythmias, which should all be managed per those conditions.
• BNP can be elevated iN CHF, AFib, ACS, PE, older age, pulm disease, renal dysfunction. BNP < 100 pg/mL or NT-proBNP < 300 pg/mL “rules out” CHF (although mind the Budolfsen 2023 study on NT-pro-BNP for cut-off threshold in patients with atrial fibrillation).

Chu Review: Rossi 2023’s lack of impact of IV calcium with diltiazem for AFib/AFlutter in the ED

This one’s a bit of a shorter one. I’d unfortunately gone on a binge of reading for that week’s journal club and had way too much on my plate, so didn’t bother writing a very long and in-depth review. Just the bullet points for this one!

Rossi, et al. 2023. Impact of intravenous calcium with diltiazem for atrial fibrillation/flutter in the emergency department. AJEM, 64, p57-61.
https://www.sciencedirect.com/science/article/pii/S0735675722007161

One Liner: IV calcium w/ IV diltiazem did not have any meaningful change to BP, hypotension, bradycardia, time to rate control, or time to achieve rate control; will not change my practice since I don’t give IV calcium anyways for this anyways.

Brief Summary:

• PICO: In patients with AFib/Aflutter w RVR (HR > 120), the intervention of adding IV calcium to IV diltiazem, compared to pts getting just IV diltiazem, measured the outcomes of [primary] change in systolic BP approx. 60 min after administration, with [secondary] time to initial and sustained rate control, change in HR, presence of hypotension, bradycardia, hypercalcemia, or IV extravasation.
• Exclusion criteria were unstable pts requiring cardioversion, pts taking other rate control Rx (e.g. amiodarone, digoxin, beta blockers), pregnant, and incarcerated individuals.
• Diltiazem monotherapy group (198 pts), Diltiazem w/ calcium (56 pts).
• A few notable differences in baseline characteristics; diltiazem + calcium group noted to have lower BP’s at baseline, greater rates of CKD, active malignancy; the diltiazem bolus was also lower in the calcium group (10 mg vs 15 mg), plus they used lower diltiazem boluses than usual dosing. The study was also under-powered in terms of pt recruitment.
• No statistically significant differences in any of the outcomes, primary or secondary.

Chu Review: RBBB and MI

Since I’m not entirely sure about sharing ECGs from papers (not sure what counts as fair use, etc.), for reviews like these, I’d encourage you to track down the paper itself so you can look at the ECGs. If it turns out that it’s okay to post the ECGs here, then I’ll see about doing that at some other time. ECGs are fun, learning to interpret them, along with learning to suture, seemed to be two of the skills that back in med school made me think, “Oh dang, I’m finally learning doctor stuff!” Plus, there’s so much stuff beyond just what was taught for Step 1. Highly, highly recommend Lilly’s Pathophysiology of Heart Disease to learn the core fundamentals, and then testing yourself on other resources like Life in the Fast Lane’s ECG library or otherwise.

Liptak, et al. 2023. ECG of the month. Annals of Emergency Medicine, 81, 1, p 79 – 83.
https://www.sciencedirect.com/science/article/pii/S0196064422005054

One Liner: RBBB’s can be markers of high mortality as well as obscure the presence of acute ischemic heart disease such as an MI; this paper won’t necessarily change my practice, but was useful for reminding me of things learnt in residency.

Brief Summary:

• Be able to interpret an ECG independently of history, as well as with history, to avoid anchor bias.
• An MI can be “hidden” in the slurred waveforms of RBBB
• PE’s can cause ischemic changes to the ECG, but should not be causing reciprocal ST segment depressions
• RBBBs are associated w higher mortality in MI, and the European Cardiology guidelines recommend PCI for new RBBB + ischemic chest pain
• Physical exam findings of heart failure should point more towards ischemic causes, e.g. acute onset CHF from MI, rather than a PE
• Bedside echo can be further used to evaluate for acute right heart strain vs ischemic focal wall motion abnormalities
• This paper won’t change my practice, but was good to remind myself of the importance in differentiating between these causes of chest pain, dyspnea, and hypoxia

Chu Review: Andersen 2021’s vasopressin and methylprednisolone lack of effect on ROSC for in-hospital cardiac arrest

Andersen, et al. 2021. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest A Randomized Clinical Trial. JAMA, 326, 16, p 1586-1594.
https://jamanetwork.com/journals/jama/fullarticle/2784625

One Liner: A multicenter placebo controlled RCT in Denmark showed very small statistically significant increase in ROSC in adults w cardiac arrest who received vasopressin + methylprednisolone + standard cardiac arrest care, as opposed to placebo + standard cardiac arrest care; this will not change my practice.

Brief Summary:

• About 500 pts who had an in-hospital cardiac arrest were randomized to either receive standard “placebo” cardiac arrest management (namely epinephrine) or received both methylprednisolone 40 mg IV + 20 Units of vasopressin as soon as possible after first dose of epinephrine. An additional 20 Units of vasopressin was given after each epinephrine dose for a maximum of 4 doses (total 80 units).
• The drugs/placebo vials were in a blinded study kit which was carried by a dedicated member of the cardiac arrest team.
• While there was a tiny statistical difference in primary outcome (achievement of ROSC favoring intervention), there were no meaningful differences in secondary outcomes (survival to 30 days, with or without favorable outcomes neurologically as measured by modified Rankins, or other organs as measured by SOFA score).
• I have concerns regarding ethical and logistical issues of getting consent for a clinical situation of cardiac arrest.
• This will not change my practice.

Chu Review: Davis 2023’s review on Hypertensive Emergencies

I absolutely love EB Medicine. My program director in residency introduced us to it during my PGY1 in 2017. It’s chockfull of great issues on core topics that everyone should know in emergency medicine. There are issues like “the back pain issue,” “the asthma issue,” “the PALS update” issue and so on. They’re more up to date than textbooks and have a lot of immediately useable information. Highly recommend getting access to them if you can, either by institution, continuing medical education funding, or otherwise. They can be a bit dense to read (most issues pass the 20 page mark easily), but they have great summaries and practice-changing points in the back. Most also have clinical pathways drawn out, too. If you have a subscription, you can also get CME credits! EB Medicine and Up to Date article reading while on or off shift are some of my main ways to pick up CME credits now that I’m out of residency and post-residency training.

This issue looks at various emergent medical conditions that present with elevated blood pressure. I’ll be honest, it’s frustrating when patient present to the ER (either on their own or sent by an outpatient clinician) purely “because of the number.” Some clinicians don’t even follow their own academy’s guidelines on this! I think every ER doc can unfortunately share in this moment, haha.

Davis, et al. Hypertensive emergencies: guidelines and best-practice recommendations. Emergency medicine practice, 25, 6.
https://www.ebmedicine.net/topics/cardiovascular/emergency-medicine-hypertensive-emergencies

One Liner: It is the presence of end organ damage which mandates immediate treatment, as opposed to just a patient w hypertension; will not change my practice, but is a good reminder

Brief Summary:

• You must be able to distinguish between “a patient with HTN” from “a patient with an actual hypertensive emergency” through the absence or presence of EOD. Pts w true HTN emergency have higher mortality and rates of requiring kidney transplants.
• Different societies and guidelines exist regarding thresholds of BP definition and management, and there are low amounts of good evidence (except in mgmt of ICH) but a general recommendation is BP > 180/110 mmHg should be evaluated promptly to see if they have signs of EOD.
• HTN emergencies more likely in > 60 yo, Black, male, uninsured, low SES, often from deranged autoregulation and dysregulation in multiple systems, including endocrine (i.e. RAAS), neuro, cardiovascular, renal. Every organ system can manifest a symptoms in the presence of hypertension (e.g. aortic dissection, HTN encephalopathy, SAH, PRES, Cushing syndrome, sclerodermal renal crisis, pre-eclampsia, toxidromes and medication side effects, etc.)
• The most common symptoms in HTN emergency include SOB, CP, HA, AMS, focal neuro deficits. Most common sequelae include pulmonary edema, heart failure, ischemic stroke, ACS, hemorrhagic stroke, aortic syndromes, encephalopathy.
• The Italian “BARKH” mnemonic can serve as a reminder, Brain, (stroke, encephalopathy), Arteries (aorta, pre/eclampsia, HELLP), Retina, Kidney (renal insuffiency, TTP-HUS), Heart (failure failure, pulmonary edema).
• Labs can include POC glucore, renal function, electrolytes, cardiac markers, CBC (can check for anemia, plt count abnormalities of TTP-HUS, anemia chronic disease, DIC, others).
• ECGs can show ischemia or strain pattern, including: ST depression w down-sloping convex ST segment and disconfordant T wave inversions in the lateral precordial leads, increased R wave amplitude in left sided ECG leads (I, aVL, V4-V6), increased S wave depth in right sided leads (III, aVR, V1-3).
• Imaging should be tailored to clinical concrens and symptoms. Note concerns of CT Brain within 6 hr for SAH, lumbar puncture, MRI may be needed for PRES. Ultrasound can check for papilledema as well.
• Treatments are predicated on signs, symptoms, and syndrome. Acute Heart failure (NIPPV, vasodilators such as nitrates, and diuresis, avoid morphine), Acute Ischemic Stroke (thrombolysis and thrombectomy get to < 180/110 mmHg, otherwise < 220/120), ACS (incl STEMI, NSTEMI, unstable angina; avoid beta blockers in high risk pts eg sysBP < 120 mmHg, age > 70, HR > 110 bpm due to higher mortality; nitrates may be useful but lack mortality benefit), ICH (drop sysBP < 140 mmHg and keep between 130-150 mmHg to lwoer mortality, limit hematoma expansion, lower rates of neuro deterioration), SAH (prevent rebleeding, poor data but general rec sysBP < 160-180 mmHg, other societies tx if MAP > 110), Aortic Dissection (first get HR to 60, then BP < 120 mmHg), HTN encephalopathy (often in BP > 220/120 mmHg, drop MAT 20-25%, see if there may be Rx like immunosuppressant, autoimmunity, renal failure), Pre-Eclampsia and Eclampsia (severe: BP > 160/110 mmHg, or 140/90 w thrombocytopenia, impaired liver function, renal insufficiency, pulm edema, new onset HA, or visual change; ACOG rec labetalol, hydralazine, PO nifedipine; magnesium 4-6 g IV load and 1-2 g/hr), Acute Renal Failure (no consensus or RCT’s)
• No specific data on when exactly to start an arterial line due to paucity of studies and proven benefit.
• Beta blockers in cocaine classical teaching, but may be overstated.
• Typical Rx used in HTN emergencies include enalaprilat (ACEi, 1.25-5 mg IV, risk of hyperkalemia, cough), esmolol (load 1 mg/kg, esp for aortic dissection), labetalol (BB and alpha blocker 20 mg IV), clevidipine (CCB 1-2 mg/hr, reflex tachycardia), nicardipine (CCB 5 mg/hr IV, reflex tachycardia), magnesium (CCB, vasodilator, antidysrhythmic, 4-6 g IV over 20-30 min, drip 1-2 g/hr, respiratory depression), hydralazine (direct arterial relaxer, 5-20 mg IV), nitroglycerin (0.5 mcg/min IV drip, HA, flushing), sodium nitroprusside (vasodilator< NO releaser, 0.5 mcg/kg/min IV, cyanide tox).

Chu Review: Petri 2023’s SLE-BRAVE-II trial of Baricitinib for SLE

Petri, et al. 2023. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II). The Lancet, 401, 10381, p1011-1019.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02546-6/fulltext

One Liner: Baricinitib unfortunately failed to meet its primary outcomes for SLE in this negative follow-up study; will not change my practice.

Brief Summary

• Clinical Question (PICO): In pts with active SLE who take the intervention of baricitinib 4 mg + SOC, compared to placebo + SOC, is there improved outcomes in [primary] proportion of pts reaching an SRI-4 response at 52 wks, and some secondary outcomes similar to the SLE-BRAVE-I trial.
• This was meant to be a follow-up to the SLE-BRAVE-I to further tease out safety and efficacy, with similar study patient population demographics, inclusion, exclusion, primary, and secondary outcomes.
• While there were very few serious adverse events, unfortunately the primary outcome was not met, and this medication is being “retired” from SLE research.