Category: Cardiology

Comparing Unnecessary ED Chest Pain Testing

Since my last post regarding the disutility of coronary CT angiograms for the evaluation of acute chest pain in the Emergency Department was so popular, here’s more: a randomized trial testing CCTA versus stress echocardiogram.

The problem: no specific functional or anatomic testing is routinely necessary in the ED.

And, hidden in this comparison are broad results typical of testing in a “low to intermediate” population with a Diamond-Forrester pre-test probability of 28% and a TIMI score of 0 to 1. Effectively, it’s unimportant to describe their comparison because the incidence of their safety outcomes over a median follow-up of 733 days is so low its virtually impossible to detect a difference. Any Major Adverse Cardiovascular Event occurred in only 4.5% of all patients – but, restricted to the endpoints relevant to the testing performed, only 3.0% had a nonfatal myocardial infarction or cardiac arrest. Any differences in throughput and resource utilization between arms will be related to specific process and protocol implementation unique to the trial institution, so even their findings with respect to their primary outcome are not likely to be generalizable.

But, back to the futility of any test – only 10% of those enrolled were referred for cardiac catheterization, and only half of those received an intervention as a result. Another 10% or so received new or increased pharmacotherapy – likely overlapping with the population undergoing catheterization. Therefore, probably 85% of patients enrolled clearly received no specific benefit from these tests, 5% probably had some benefit, 5% were harmed (excess revascularization, serious complications), and 5% are equivocal.

And, all of this on the foundational premise these tests need to be performed widely, and in the ED. True disease is rare in this population, and the timeliness of diagnosis of CAD does not need to be made at the index visit. This is not high-value medical care.

“Coronary Computed Tomography Angiography Versus Stress Echocardiography in Acute Chest Pain: A Randomized Controlled Trial”

https://www.ncbi.nlm.nih.gov/pubmed/29909113

And Here’s Why CTCA Is Useless

In the Emergency Department, that is, at least.

A few years ago, there were several major studies evaluating the safety of a CT coronary angiogram-based study for the evaluation of chest pain in the Emergency Department. These studies consistently found the CTCA is sensitive for coronary artery plaque – and, thus, patients with troponin-negative chest pain syndromes and clear coronary arteries could be discharged from the ED.

The constant challenge, however, has been specificity – not only with respect to whether the CT can accurately detect stenoses, but the clinical relevance of the stenoses. Non-obstructive, moderate, and high-grade stenoses detected on CTCA all trigger further evaluation – either non-invasive or invasive, with subsequent interventions of uncertain clinical value.

This small propensity-matched study from a cohort of 25,251 patients undergoing CTCA picked out 234 pairs of patients, matching those who had an acute coronary syndrome during follow-up with those who did not. And, yes, those with ≥50% or ≥70% stenosis were more likely to suffer an ACS, but not my much. The vast majority – 62% – of those with an ACS in follow-up had non-obstructive coronary disease. Indeed, just over half of patients with an ACS even had their culprit lesion identified on the initial CTCA. The degree of stenosis was mildly predictive of future ACS, but plaque burden between those who suffered an event and those who did not was similar. The most predictive feature, however, was composition of non-obstructive plaque, including fibrofatty features and necrotic core.

This is why CTCA is unhelpful in the Emergency Department. It does, yes, accurately detect patients without coronary disease – but this target “low-risk” population already has such a low pretest likelihood of poor outcome the added value is nil. Then, the “true positives” from these studies – stenoses and interventions – are not equivalent to ACS prevented.

Friends don’t let friends do CTCA in the ED – it doesn’t add value or prevent adverse outcomes.

“Coronary Atherosclerotic Precursors of Acute Coronary Syndromes”
http://www.onlinejacc.org/content/71/22/2511

EDACS vs. HEART – But Why?

The world has been obsessed over the past few years with the novelty of clinical decision rules for the early discharge of chest pain. After several years of battering the repurposed Thrombolysis in Myocardial Infarction (TIMI) score, History, Electrocardiogram, Age, Risk factors and Troponin (HEART) became ascendant, but there are several other candidates out there.

One of these is Emergency Department Assessment of Chest pain Score (EDACS), which is less well-known, but has reasonable face validity.  It does a good job identifying a “low-risk” cohort, but is more complicated than HEART. There is also a simplified version of EDACS that goes ahead and eliminates some of the complicated subtractive elements of the score. This study pits these various scores head-to-head in the context of conventional troponin testing, as well.

This is a retrospective review of 118,822 patients presenting to Kaiser Northern California Emergency Departments, narrowing the cohort to those whose initial Emergency Department evaluation was negative for acute coronary syndrome. The 60-day MACE (composite of myocardial infarction, cardiogenic shock, cardiac arrest, and all-cause mortality) in this cohort was 1.9%, most of which were acute MI. Interestingly, these authors chose to present only the negative predictive value of their test characteristics, which means – considering such low prevalence – the ultimate rate of MACE in all the low-risk cohorts defined by each decision instrument were virtually identical. Negative predictive values of all three scores depended primarily on the troponin cut-off used, and were ~99.2% for ≤0.04 ng/mL, and ~99.5% for ≤0.02 ng/mL. The largest low-risk cohort by definition was with the original EDACS rule, exceeding the HEART score classification by an absolute quantity of about 10% of the total cohort, regardless of the troponin cut-off used.

The editorial accompanying the article goes on to laud these data as supporting the use of these tools for early discharge from the Emergency Department. However, this is an outdated viewpoint, particularly considering the data showing early non-invasive evaluations are of uncertain value. In reality, virtually all patients who have been ruled-out for ACS in the ED can be discharged home, regardless of risk of MACE. The value of these scores is probably less so in determining who can be discharged, but rather in helping triage patients for closer primary care or specialist follow-up.  Then, individualized plans can be developed for optimal medical management, or for assessment of the adequacy of the coronary circulation, to prevent what MACE is feasible to be prevented.

“Performance of Coronary Risk Scores Among Patients With Chest Pain in the Emergency Department”
http://www.onlinejacc.org/content/71/6/606

“Evaluating Chest Pain in the Emergency Department: Searching for the Optimal Gatekeeper.”
http://www.onlinejacc.org/content/71/6/617

Would You Use A Syncope SDM Instrument?

Much has been made, off and on, about the chest pain shared decision-making tool rolled out over the past couple years. It turns out, when properly informed of their low risk for subsequent cardiac events, most patients look at you sideways and wonder why anyone was offering them admission in the first place.  Whether that was its intended purpose, or a happy little accident, is a subject of controversy.

Their next target: syncope.

The content of this article is not very profound, other than to show the first step in the process of developing such an SDM instrument. These authors detail their involvement of emergency physicians, cardiologists, and patient stakeholders to inform their iterative design process. In the end, their tool looks a lot like the their chest pain instrument:

Generally speaking, because the approach to low-risk syncope has some of the same issues as low-risk chest pain, I have essentially the same fundamental problems. Much like for chest pain, inpatient evaluations for syncope are generally unrevealing. We probably ought not be admitting most of these patients. Therefore, this SDM instrument is again addressing the problem of low-value resource utilization by shifting the burden of the decision onto the patient, and trying to convince them to make what we already know to be the correct one (go home). That’s not how the Force works.

Then, just like the chest pain tool, this fails to convey the benefit of hospitalization for comparison. In their pictogram, two out of 100 patients suffer an adverse event after fainting. Is admission to the hospital protective against those adverse events – even if a diagnosis is made? The patient needs to receive some simplified visualization of their expected benefit from staying in the hospital, not just simply the base rate for deterioration.

I love shared decision-making. I use it constantly in my practice in situations where the next step in evaluation or treatment has no clearly superior path. Again, I don’t think this reflects the same uncertainty.

“Development of a Patient Decision Aid for Syncope in the Emergency Department: the SynDA tool”

https://www.ncbi.nlm.nih.gov/pubmed/29288554

Yet Another Failure to Prevent Contrast-Induced Nephropathy

I’m not the first one to this party, but this is worth a short note to touch upon, regardless, in case you missed it before the holiday break. I’ve written about retrospective propensity-matched analyses and other data suggesting the impact of contrast administration on acute kidney injury is overstated. This is yet another piece of the puzzle supporting these conclusions.

This is a beautifully massive trial, the PRESERVE Trial, with 5,177 patients enrolled in a 2×2 factorial design to test the impact of sodium bicarbonate and acetylcysteine on kidney injury following coronary angiography. This study was conducted in the United States, Australia, Malaysia and New Zealand, and was planned to enroll 7,680 to detect an increase in the primary end point of 8.7% to 6.5% for each trial intervention. As you might now have gathered, they stopped the trial early after an interim analysis when their statistical analysis met criteria for futility. The incidence of the primary end point, a composite between increase in creatinine, dialysis, and death, was effectively identical between each of the various arms, as were non-renal adverse events.

The short takeaway from these data: if contrast-induced nephropathy cannot be prevented by any available treatment, is it a true clinical entity at the doses currently used in clinical practice? Or, rather, do the clinically ill simply suffer kidney injury, regardless?

“Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine”
http://www.nejm.org/doi/full/10.1056/NEJMoa1710933

The Syncope Prophecy

There has been a lot of research regarding the disposition of patients with syncope from the Emergency Department. Unfortunately, to put it bluntly, little of it is effectively usable in general practice. The most recent AHA Syncope guidelines offer loose guidance patients should have risk-stratification performed prior to disposition, but their summary of decision-instruments admits the limitations of each.

And, as it turns out, we know better, anyway.

In this prospective study, Emergency Physicians explicitly recorded the suspected etiology of syncope at the time of disposition, choosing from four broad categories: vasovagal, orthostatic hypotension, cardiac, other/unknown. Physicians were also asked to rate their level of confidence regarding their diagnosis on a scale from 0% to 100%. Research personnel then performed typical observational follow-up to determine 30-day adverse outcomes.

Over the ~4 year study period, 5,010 patients were included in the final analysis. The average age was 53 years, with a wide standard deviation of 23 years. Generally speaking, most patients were healthy, with hypertension the most prevalent known underlying medical condition at 31.6%. Over 90% of patients had ECG and blood testing in the ED, with a minority receiving any radiography. Over half (53.3%) of the cohort received a provisional diagnosis of vasovagal syncope, with 32.2% “other/unknown”, 9.1% orthostatic hypotension, and 5.4% cardiac causes.

The good news: only 1.0% of the vasovagal cohort had an adverse outcome within 30 days, none of which were death. Then, as expected, 20.9% of the cohort with suspected cardiac cause suffered a serious outcome, although, only 0.8% died – an actuarially interesting statistic, considering the average age of this cohort was 86.5 years. The other large cohort of patients, those with “unknown” etiology, suffered serious outcomes 4.8% of the time, and their outcomes were spread evenly across the various cardiac and non-cardiac outcomes.

A long story short, then – physicians do a pretty good job of identifying those who are at low risk and high risk for serious outcomes.  Considering the imprecision of decision instruments and their limitations, it turns out the best computer … is probably still the trained brain.  These data don’t have quite the granularity to decipher whether the low rates of adverse outcomes in the “other/unknown” cohort were otherwise related to specific diagnoses or underlying comorbidities, but it’s not a stretch to speculate physicians probably could also have prognosticated fairly well on gestalt even within this category.

Worth noting, as well, in comparison to the PESIT study, the prevalence of undiagnosed pulmonary embolism in this population was 0.2%.

“Syncope Prognosis Based on Emergency Department Diagnosis: A Prospective Cohort Study”

https://www.ncbi.nlm.nih.gov/pubmed/29136314

The Top “Overuse” of 2016

Another entry in JAMA Internal Medicine’s lovely “Less is More” series, this is a “systematic review” of the previous year’s literature regarding potentially unnecessary care. Living here in the asylum, it seems all our fellow inmates and I are consigned to issuing weather reports from the tempest – but, hey, baby steps.

Their “systematic review” is not particularly rigorous.  It’s basically a literature search, followed by a subjective distillation by author consensus to those considered to be the most potentially impactful – but, regardless, their list is worth reviewing. Without further ado, the highlights of their ten selections:

  • Transesophageal echocardiography is more informative than transthoracic in illuminating the etiology of a stroke, but the additive information does not have a clear downstream benefit on outcomes.
  • Patients undergoing computed tomography to rule out pulmonary embolism without algorithm-compliant use of D-dimer suffer from overuse and low-value testing.
  • CT use increased in all Emergency Department patients with respiratory symptoms, with no evidence of downstream change in prescribing, hospital admission, or mortality.
  • Supplemental oxygen does not demonstrate benefit in patients with chronic obstructive pulmonary disease and mild exertional hypoxia.
  • Small improvements in antibiotic prescribing were seen when comparisons to peers were performed.
  • A shared decision-making implementation for Emergency Department patients with chest pain increased patient engagement and demonstrated a secondary effect of diminished admission and cardiac testing.

Wizard.

“2017 Update on Medical Overuse: A Systematic Review”
https://www.ncbi.nlm.nih.gov/pubmed/28973402

Are We Killing People With 30-Day Readmission Targets?

Ever since the Center for Medicare and Medicaid Services announced their intention to penalize hospitals for early readmissions, folks have been worrying about the obvious consequences: would a focus on avoidance place patients at risk? Would patients best served in the hospital be pushed into other settings for suboptimal care?

That is the argument made in this short piece in the Journal of the American College of Cardiology. They look backwards at the last two decades of heart failure readmissions and short-term mortality, and take issue with the fundamental underlying premise of the quality measure, the inequities associated with the measure, and potential unintended harms. Their most illustrative example: when patients die outside the hospital within 30-days, paradoxically, they contribute to apparent improved performance in healthcare quality, as measured by 30-day readmission.

They back up their point by using the aggregate data analyzing readmissions between 2008 and 2014, published previously in JAMA, and focusing primarily on the heart failure component. In the original JAMA analysis, the evaluation paired individual hospital monthly readmission and risk-adjusted mortality, and were unable to identify an increased risk of death relating to reductions in 30-day readmissions. These authors say: too much tree, not enough forest. In the decade prior to announcements of 30-day readmission penalties, 30-day heart failure mortality had dropped 16.2%, but over the analysis period, 30-day heart failure mortality was back on the rise. In 2008 the 30-day mortality was 7.9% and by 2014 it was up to 9.2%, a 16.5% increase, and an even larger increase relative to the pre-study trend with decreasing mortality.

These are obviously two very different ways of looking at the same data, but the implication is fair: those charged with developing a quality measure should be able to conclusively demonstrate its effectiveness and safety. If any method of analysis raises concerns regarding the accepted balance of value and harm, the measure should be placed on a probationary status while rigorous re-evaluation proceeds.

“The Hospital Readmission Reduction Program Is Associated With Fewer Readmissions, More Deaths”
http://www.sciencedirect.com/science/article/pii/S0735109717393610

Predicting Poor Outcomes After Syncope

Syncope is a classic good news/bad news presenting complaint. It can be highly distressing to patients and family members, but rarely does it relate to an acutely serious underlying cause. That’s the good news. The bad news, however, is that for those with the worst prognosis, most of the poor prognostic features are unmodifiable.

This is a prospective, observational study of patients presenting with syncope to Emergency Departments in Canada, with the stated goal of developing a risk model for poor outcomes after syncope. The composite outcome of interest was death, arrhythmia, or interventions to treat arrhythmias within 30 days of ED disposition. Follow-up was performed by structured telephone interview, networked hospital record review, and Coroner’s Office record search.

To achieve a lower bound of the 95% confidence interval for sensitivity of 96.4%, these authors targeted a sample size of 5,000 patients, and ultimately enrolled 5,010 with complete outcome assessments. The mean age was 53.4, had a low incidence of comorbid medical conditions, and only 9.5% were admitted to the hospital. Within 30 days, 22 had died, 15 from unknown causes and the others from the pool of 91 patients diagnosed with a “serious arrhythmia” – sinus node dysfunction, atrial fibrillation, AV block, ventricular arrhythmia, supraventricular tachycardia, or requiring a pacemaker insertion.

These authors ride the standard merry-go-round of statistical analysis, bootstrapping, and logistic regression to determine a prediction rule – the Canadian Syncope Arrhythmia Risk Score – an eight element additive and subtractive scoring system to stratify patients into one of eleven expected risk categories. They report the test characteristics of their proposed clinically useful threshold, greater than 0, to be a sensitivity of 97.1% and a specificity of 53.4% – a weak positive predictive value of 4.4% considering the low incidence of the composite outcome.

This is yet another product of obviously excellent work from the risk model machines in Canada, but, again, of uncertain clinical value. The elements of the risk model are frankly those that are quite obvious: elevated troponin and conduction delays on EKG, along with an absence of classic vasovagal features. These are patients whose cardiac function is obviously impaired, but short a time machine to go back and fix those hearts before they became sick, it’s a bit difficult to see the path forward. These authors feel their prediction rule aids in safe discharge of patients with syncope, although these patients are already infrequently admitted to the hospital in Canada. The various members of their composite outcome are not equally serious, preventable, or treatable, limiting the potential management options for even those falling into their high-risk group.

As with any decision instrument, its value remains uncertain until it is demonstrated the clinical decisions supplemented by this rule lead to better patient-oriented outcomes and/or resource utilization than our current management in this cohort.

“Predicting Short-Term Risk of Arrhythmia among Patients with Syncope: The Canadian Syncope Arrhythmia Risk Score”

https://www.ncbi.nlm.nih.gov/pubmed/28791782

Neither Benefit Nor Harm Seen With Oxygen in Myocardial Infarction

We’ve been hanging on to the biological hypothesis of treating ischemia with supplemental oxygen for quite some time – despite some evidence to the contrary with regard to damage from oxygen free radical formation. What’s needed is a large, randomized trial – and so we have DETOX2-AMI, run through the SWEDEHEART trial registry.

This trial randomized individual patients with suspected or known myocardial infarction to continuous oxygen therapy or ambient air.  Patients were excluded from enrollment if they had oxygen saturation below 90% at baseline, or were not Swedish national citizens as necessary for long-term follow-up. These patients actually received fairly vigorous oxygen therapy, far exceeding the typical nasal cannula oxygen we see on patients arriving via EMS – patients randomized to the oxygen arm received 6 liters per minute via face mask for 6 to 12 hours.

Over the 1.5 year trial period, these authors enrolled 6,629 patients, generally evenly matched with regard to baseline clinical characteristics, and 75% of whom ultimately had a final diagnosis of myocardial infarction.  Detailed outcomes, owing to the underlying registry infrastructure, are scant – as compared to the AVOID trial, in which many patients underwent cardiac MRI to evaluate infarct size and ejection fraction. What you get are the hard outcomes: death and rehospitalization with myocardial infarction – and there is no difference, both in the short- or long-term, and in both the intention-to-treat and per-protocol analyses. The authors also include median highest troponin T as a surrogate for infarct severity and morbidity, and there is no difference there, either.

The underlying hypothesis here was to demonstrate a beneficial effect to oxygen in myocardial infarction – defined as a clinically relevant effect size of 20% lower relative risk of death – and that threshold was clearly not met.  There are some small differences with regard to oxygen delivery, as compared to AVOID, with the AVOID trial delivering oxygen at a much higher concentration.  But, effectively, the takeaway from these data is: oxygen just probably doesn’t matter enough to be clinically relevant. There’s no reason to be condescending and militant about taking the oxygen off a patient with myocardial infarction, and likewise it’s reasonable to consider it a wasteful intervention with regard to canistered oxygen supply.

Finally, just for fun, to recap the anachronistic acronym MONA:

Morphine – Possible small harms, as relating to inhibition of antiplatelet agents.
Oxygen – Almost certainly irrelevant with regard to clinical outcomes.
Nitroglycerin – Likely irrelevant with regard to clinical outcomes.
Aspirin – Still good!

“Oxygen Therapy in Suspected Acute Myocardial Infarction”
http://www.nejm.org/doi/full/10.1056/NEJMoa1706222