Category: Chest Pain

More Discharges With HEART

Although, the observed improvements are probably more a result of their preposterously high initial admit rate.

The HEART score, already evangelized in multiple venues, is a tool for risk-stratifying chest pain patients in the Emergency Department.  Its advantage over other, competing scores such as GRACE and TIMI, is its specific derivation intended for use in the Emergency Department.  This trial, of note, is one of the first to do more than just observationally report on its effectiveness.  These authors randomized patients to the “HEART Pathway” or “usual care”.  The HEART Pathway was a local decision aid, combining the HEART score and 0- and 3-hour troponin measurements.  Patients with low-risk HEART scores (0 to 3) were further recommended to treating clinicians for discharge from the Emergency Department without additional testing.  The primary outcome was rate of objective cardiac testing, along with other secondary outcomes related to resource utilization.  Patients were also followed for 30-day MACE, with typical endpoints for cardiovascular follow-up.

With 141 patients each arm, the cohorts were generally well-balanced – specifically with regard to TIMI score >1 and accepted cardiovascular comorbidities.  Stunningly, 78% of the usual care cohort was hospitalized at the index visit.  Thus, the mere 60% hospitalized in the HEART pathway represented a massive improvement – and, such difference likely played a role in the 57% vs. 68% reduction in objective cardiac testing within 30 days.  17 patients suffered MACE, all at the index visit – and, even though the trial was not powered for safety outcomes, none occurred in the “low risk” patients of the HEART cohort.

The authors go on to state strict adherence to the HEART pathway could have eked out an additional 6% reduction in hospitalization.  Certainly, in a nearly 80% admit rate environment, scaling back to a 54% rate is an important reduction.  But, considering only 6% suffered an adjudicated MACE, there remains a vast gulf between the number hospitalized and the number helped.  Some non-MACE patients probably derived some benefit from their extended healthcare encounter as a result of better-tailored medical management, or detection of alternate diagnoses, but clearly, we can do better.

“The HEART Pathway Randomized Trial – Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge”

All You Need is A Good History

The oft-repeated mantra in medicine is the history and, to a lesser extent, physical examination, hold the vast majority of the clues necessary for appropriate diagnosis and treatment.  Such wisdom, handed down by sages trained in the pre-penicillin era, is reinforced throughout medical training.

While such platitudes may have an element of truth, unfortunately, the patient may in fact be the least-qualified person to provide said history.

These authors compared two data sources, the Medicare claims database and a self-reported Health and Retirement Study, looking for the diagnosis of acute myocardial infarction.  Of the 45,335 patients verified in both data sources, 3.1% self-reported having an acute MI during the preceding 2.5 years.  However, only 32.3% of those could be verified using Medicare claims data; using acute coronary syndrome as a broader definition of AMI verified the self-reported history in only 48.7%.  Conversely, of the 1.4% of patients for whom Medicare claims data indicated an acute MI, only 67.8% self-reported the event.  90.5%, at least, did state they had heart problems.

So, your undifferentiated elderly patient may or may not have had an acute MI, regardless of what they actually report.  These results are mildly surprising, considering it is reasonable to expect the general public to have sufficient health literacy to understand a major diagnosis like “heart attack”.  Then again, anyone working in the Emergency Department knows the profound challenges of extracting reliable information from the undifferentiated patient.

“Comparison of Self-Reported and Medicare Claims-Identified Acute Myocardial Infarction”
http://www.ncbi.nlm.nih.gov/pubmed/25747935

Thanks to @bloodman for the article!

One Troponin is All You Need

The newer, highly-sensitive troponin assays have their pitfalls.  Specifically, specificity.  However, most of the issues associated with diminished specificity are iatrogenic – transitioning from use of troponin as a dichotomous test that used to tell us “yes” to one that does a better job of telling us “no”.

This is a pre-planned substudy as part of a prospective evaluation of patients with chest pain and non-diagnostic ECG, prospectively evaluated for acute coronary syndrome.  These authors looked at hsTnI, but, rather than using the 99th percentile as their cut-off for “negative”, they evaluate the utility of an undetectable hsTnI – which, for this Siemens assay, was <0.006 µg/L.  Based on 1,076 patients evaluated, 647 had an undetectable troponin at initial presentation.  Of these, 4 patients had a subsequently detectable troponin and were adjudicated as acute MI, 3 of which had coronary artery disease and received revascularization.

What was special about those four patients?  Each of them presented within 2 hours of symptom onset.  All told, 399 patients presented more than 2 hours after the onset of symptoms, had an undetectable troponin, and were free of MACE at 7 and 30 days.  These results are generally consistent with other work looking at the sensitivity of the (duh) highly-sensitive troponin assays – capable of conferring an excellent instant rule-out.

So, if you’re asking the question – does this patient have an acute MI? – you’re in good shape.  However, if you’re using highly-sensitive troponin assays, you’ll also need to be smart about appropriately interpreting the indeterminate range – or your patients will ultimately suffer as a result of decreased specificity and downstream over-testing.  Lastly, this is only valid as a diagnostic tool for acute MI – the extent to which it provides prognostic or diagnostic information regarding acute coronary syndromes, coronary artery disease, or ischemic heart disease is still being refined.

“Does undetectable troponin I at presentation using a contemporary sensitive assay rule out myocardial infarction? A cohort study”
http://www.ncbi.nlm.nih.gov/pubmed/25552547

A Thicket of Coronary Disease Prognostications

This recent article out of JAMA garnered headlines primarily for the insight into the risk of non-obstructive coronary artery disease – headlines such as: “Risk of Heart Attack Jumps with Non-Obstructive Heart Disease” or “Increased Risk Found For People With Even ‘Minor’ Narrowing of Heart Arteries”.

Somehow, this is profound – that individuals with measurable atherosclerotic plaque are at greater danger of suffering an acute coronary syndrome than those without.  And, frankly, despite this “significantly increased risk”, the most interesting insights – from an Emergency Medicine standpoint – are tied to how low the risks of MI were, overall.

This is a Veterans Affairs database of coronary angiography findings observed on “elective” cardiac catheterization – meaning the indication for coronary angiography in all cases was not associated with an acute coronary syndrome.  Most cases were referred primarily for chest pain, with a minority for a positive functional study.  Catheterization findings were classified as non-obstructive, 20-70% stenoses, or >70%/>50% left main stenoses, subdivided into single, double, or triple vessel disease.  Center for Medicare Services data was queried to determine 1-year outcomes, specifically myocardial infarction or death from any cause.

As expected from a VA study, the cohort is mostly male and aged between 50 and 70 years.  Nearly all had a history of hypertension and hyperlipidemia, while smoking, diabetes, and obesity were well-represented.  In short, exactly the folks you’d expect to refer for catheterization in the setting of chest pain – the sort of individual every Emergency Physician would consider “high risk”.

But the catheterization only revealed obstructive coronary artery disease in about half of these patients.  And, among those, only a little more than half received an intervention associated with angiography – either PCI or CABG.  The remainder were amenable only to medical intervention.  But, even in this cohort with pervasive vascular disease, the 1-year rate of MI was only between 1.18% and 2.47%, depending on the number of vessels involved.  Then, if non-obstructive disease was found, the 1-year rate of MI falls to 0.24% to 0.59%.  And, those without CAD had a 0.11% incidence of MI within a year.

My takeaway from all this?  As a whole, even this highest-risk cohort has a combined ~1% risk of MI within a year – meaning one could theoretically discharge nearly every chest pain patient from the Emergency Department if proper short-term follow-up were in place, and the number of adverse outcomes would be a tiny fraction of a percent.  [Add:  Stephen Smith takes issue with the generalizability of this elective catheterization cohort to our Emergency Department population, and suspects we have a much higher prevalence of unstable plaques – and potential for a greater number of adverse events.]

What’s unfortunate in the data presented, however, are few obvious differences between those who had severe – even 3-vessel disease – and those who had no disease whatsoever.  In aggregate, even though the differences met statistical significance, the absolute differences were small.  Indications were similar between groups, comorbid disease was similar between groups, and, perhaps, those with more advanced disease were slightly older.  Perhaps some type of matching algorithm could be used to generate more precise, individualized estimates for individual patients, but such is just speculation.

“Nonobstructive Coronary Artery Disease and Risk of Myocardial Infarction”
http://jama.jamanetwork.com/article.aspx?articleid=1920971

The 2014 AHA NSTE-ACS Guidelines

One of the best things about Emergency Medicine is the preponderance of guidelines imposed upon our management of patients by non-Emergency Medicine clinicians.  One of the most glorious offenders is the American Heart Association, dictating our care of Stroke and Acute Coronary Syndrome.

But, actually, this most recent update – despite the continued absence of Emergency Medicine from the Writing Committee – contains some interesting subtle shifts.  Out of its 150-odd pages of content and evidence, most of the Emergency Medicine-relevant content is in Section 3: Initial Evaluation and Management.  Many of the guidelines are not controversial – send patients with suspected ACS to the Emergency Department, give aspirin, obtain an ECG, etc.

But, as a Class I recommendation, they note patients with suspected ACS can be risk-stratified based on likelihood of ACS to decide on the need for hospitalization.  They also now include an expanded discussion of tools beyond the old stalwarts TIMI and GRACE, incorporating ED-centric tools such as the Vancouver Rule, the HEART score, and the HEARTS3 score.  This greatly expands guideline-based backing of these rules for shared decision-making with patients, and, frankly, makes the previously “mandatory” observation of patients with chest pain less so.

The next interesting bit relevant to the ED lay in subsection 3.4.1 – the use of biomarkers.  I’ll just reproduce my favorite bit here:

Class III: No Benefit
1. With contemporary troponin assays, creatine kinase myocardial isoenzyme (CK-MB) and myoglobin are not useful for diagnosis of ACS (158-164). (Level of Evidence: A)

The guidelines also imply, if symptom onset can be reliably determined, a single troponin measurement is reasonable 6+ hours after onset, or, for shorter onset timeframes, a troponin on arrival and a second as few as 3 hours after onset is reasonable to detect rising or falling levels.  And, beautifully, in subsection 3.5.1, all recommendations regarding discharge from the ED are Class IIa, only make weak recommendations for the reasonableness of observation, and acknowledge most patients with chest pain do not have ACS, and most are not at risk of ACS.

There is ample further fodder for the interested reader to pick apart recommendations and conflicts of interest – particularly with regards to the incorporation of newer antiplatelet agents – but, I’m generally pleased with the general direction of this guideline, as it applies to our practice.  However, this does not preclude the need for ACEP to develop its own Clinical Policy, to further guide and protect both patients and Emergency Physicians.

“2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines”
http://circ.ahajournals.org/content/early/2014/09/22/CIR.0000000000000134.full.pdf+html

Highly Sensitive Troponins – False Positive Bonanza

The “highly sensitive” troponin has received a great deal of publicity, hyped ad nauseum, see: “Simple test could help rule out heart attacks in the ER.”

But, as sensitivity increases – invariably, specificity decreases.  However, that is not the fault of the test – it is a failure of clinicians to ask the correct question of the test.  When asking “does this patient have an acute myocardial infarction?”(most commonly Type 1 MI in the ED), our training and education has been outpaced by assay technology – the test no longer provides a dichotomous “yes” or “no”.

This publication provides a lovely window into precisely the added value of the hsTnI compared with conventional TnI, both assays by Abbott Laboratories.  In this study, the authors simultaneously drew research samples of blood any time a cTnI was ordered.  The sample was frozen, and then analyzed at least 1 month following presentation.  Authors performed hospital records review, telephone follow-up, and vital records search to evaluate adverse events in patients with hsTnI or cTnI elevation.

Overall, they enrolled 808 patients, 40 of which received an adjucated diagnosis of “acute coronary syndrome” – 26 with AMI and 14 with unstable angina.  61 patients had acute heart failure, 7 had volume overload, 7 had pulmonary emboli, and 41 had other non-ACS cardiac diagnoses.

All told, there were 105 elevated cTnI samples – and 164 elevated hsTnI samples.  This means, essentially – in the acute setting, asking our question of interest – there were 50% greater false positives associated with hsTnI.  No patients would have been reclassified as nSTEMI based on the hsTnI result.  The authors sum this up nicely in their discussion:

“The preponderance of novel elevations (roughly 10% in this study) will be observed mainly in subjects with non-ACS conditions.”

The authors go on to note the value in detecting these novel or detectable troponin levels – essentially, non-ACS, subclinical disease – with a much poorer long-term prognosis.  This is almost certainly the case, although it will require further investigation to reliably demonstrate cost-effective management strategies based on these results.

“Troponin Elevations Only Detected With a High-sensitivity Assay: Clinical Correlations and Prognostic Significance”
http://www.ncbi.nlm.nih.gov/pubmed/25112512

Addendum:  As Stephen Smith points out, it may be possible to use the greater precision of hsTnI at the low end of the assay to more accurately adjudicate some MI.  Great insight!

Highly-Sensitive, But Not Highly Valuable

There is a great deal of continuing debate raging over the use of “high sensitivity” troponins in the Emergency Department.  But, it’s not the test alone at fault – the responsibility for interpreting and acting upon the results lay with clinicians.  In the era of conventional troponins, the test was a powerful tool to rule-in myocardial infarction.  With high sensitivity troponins, the greater value in the tool is in ruling-out.

However, while much is made of the theoretical beneficial test characteristics of high sensitivity troponins, few have measured actual patient-oriented outcomes.  This group from Valencia, Spain, prospectively evaluated consecutive patients at a single institution as their laboratory switched from a conventional TnI assay to a highly sensitive one.  Comparing 699 consecutive patients from the pre-hsTnI period to 673 consecutive patients in the post-hsTnI … there were too many baseline differences to draw any useful conclusions.

But, in an effort to salvage the paper, the authors perform a propensity-score matching algorithm to balance to cohorts.  Based on these matched cohorts, for which they do not offer much in the way of detail, there were no differences in major adverse cardiac events or death at 6-month follow-up.  Regarding management decisions after the change, they note patients were less likely to undergo non-invasive testing in a chest pain observation unit, but substantially more likely to undergo invasive procedures.

This is just a single-center experience, and their observations are incontrovertibly corrupted by the unfortunate change in patients characteristics across their study periods.  It does, at least, provide some small window into how hsTnI might impact the management pathway for patients presenting with chest pain.

“High-sensitivity versus conventional troponin for management and prognosis assessment of patients with acute chest pain”
http://heart.bmj.com/content/early/2014/06/19/heartjnl-2013-305440.abstract

A Shared Decision-Making Trial … But Fatally Flawed?

Shared decision-making is developing as the proposed solution to many of the problems with resource utilization today.  Rather than embrace “zero miss” practice without properly involving patients as the decision-makers, we are now encouraged to offer the patient choices regarding their diagnostic and treatment decisions.  By sharing the decision – and the risk – I find patients quite amenable to forgoing much low-yield testing.

To that end, a multi-center trial has begun, evaluating the use of shared decision-making in low-risk chest pain.  The trial is based on an information graphic created by the Mayo Clinic, and individualized risk assessment is supported by Jeff Kline’s attribute-matching algorithms.  This is fabulous, from a conceptual standpoint – as shared decision-making is not nearly as feasible without the proper communication tools or best available evidence available at the point of care.

However, there’s an important missing element from the proposed information graphic:

Link to high-resolution version.

The decision tool explains the 45-day risk of myocardial infarction if testing is deferred.  However, the patient-oriented decision is between stress test (or CT coronary angiogram, at the University of Pennsylvania), cardiology follow-up, and primary care follow-up – and the decision aid doesn’t actually address those choices.  It does not describe the relative risks of MI between each option, and, more importantly, it does not describe the risks or benefits of the additional testing offered.  Without information regarding the rates of true positive and false positive test results, the incremental prognostic value of such tests, or the costs associated with additional testing, the patient doesn’t have the appropriate foundational information for their choice.

Conceptually, this is a fantastic trial.  However, I’m not sure the decision-aid has been correctly designed and implemented, with regard to the choices offered.  Indeed, if the poor test characteristics of stress and CTCA in this population were shared with patients, it would probably even show more powerful reductions in resource utilization.

“Effectiveness of the Chest Pain Choice decision aid in emergency department patients with low-risk chest pain: study protocol for a multicenter randomized trial”
http://www.trialsjournal.com/content/15/1/166

The Unusable Manchester Chest Pain Instrument

With probably underpowered derivation and validation, a model that seems to overfit the data, and incorporating an impractical and questionable cardiac biomarker – despite a lovely continuous predictive function – this instrument is doomed in its current form.

This is the Manchester Acute Coronary Syndromes (MACS), a prospectively derived and validated risk-stratification instrument.  These authors identify an 8 variable decision instrument based on 698 patients at Manchester Infirmary – including hsTnT, heart-type fatty-acid binding protein, ECG changes, diaphoresis, vomiting, radiation to right shoulder, worsening angina, and hypotension – and then validate it on 463 patients from Stepping Hill Hospital.  In the validation, 27.0% of patients were ultimately classified as “very low risk” with 98% sensitivity (95% CI 93.0% to 99.8%) for 30-day MACE, and the authors feel this tool could reduce unnecessary admissions.

My favorite feature from this study is the derivation of a continuous function for prediction of 30-day outcomes.  The authors state an AUC of 0.92 for the function predicting MACE, which suggests potential as a useful tool for discussing individualized risks with patients.  Rather than simply dichotomize a “very low risk” cohort, the predictive function could help aid shared decision-making conversations with patients.

However, the utilization of fatty-acid binding protein is questionable.  These same authors presented work favoring H-FABP with an AUC for diagnosis of AMI of 0.86, but compared it against a troponin assay with an AUC of 0.70.  A response to that same article notes the authors probably made inappropriate comparisons, and modern conventional troponin assays and/or high-sensitivity troponin assays have AUCs >0.90.  It’s not clear what, or how much, additional value this biomarker adds to this study – and its inclusion essentially obviates the generalizability of the tool.  No rapid, automated H-FABP assay is available suitable for use in an ED context.  It is also unfortunate the corresponding author declares conflict-of-interest with the manufacturers of the assays used.

Interestingly, as well, the authors focus only on the “very low risk” group when an odd thing happens in their validation population – the “low risk” group actually had fewer MACE than the “very low risk” group (1.2% vs. 1.6%).  This is a substantial reversal of the derivation population (5.8% vs. 0.4%), suggesting the attempted validation reveals their model may be overfitting the data.  The authors state the second site validation is a strength regarding combating overfitting, but do not mention this inconsistency in the outcomes.

And, finally, I’m not entirely certain what question this study was designed to answer.  The focus on a “very low risk” cohort in the discussion doesn’t entirely match the study design – it seems other studies focused on outcomes in low risk chest pain have specifically excluded patients whose presentation is clearly AMI on initial presentation.  The inclusion of the entire spectrum of disease, while valuable for their general model, dilutes the strength of their “very low risk” conclusions, as evidenced by wide confidence intervals around the sensitivity for MACE.

As the authors note in their discussion, additional work needs to be done to compare their model with other risk-stratification tools.  And, for anyone to use this tool other than the authors, the H-FABP needs to be dropped.  At the least, however, it fits in nicely with another recent critique – that many “low risk” and “very low risk” patients do not require observation and immediate provocative testing, where the false-positives and resource expenditures are simply preposterous.

“The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation”
http://heart.bmj.com/content/early/2014/04/29/heartjnl-2014-305564

Burn the ACC/AHA Low-Risk Chest Pain Guidelines

Management of low-risk chest pain is, by reasonable conjecture, one of the greatest failings of Emergency Medicine and the medical profession in general.  Whether driven by true altruism or by risk-management and zero-miss strategies based on the ACC/AHA guidelines, many, many, many patients are admitted and subjected to provocative testing.

And almost none of those patients are ultimately, correctly, diagnosed with the feared disease – acute coronary syndrome.

This is a prospective, observational evaluation of patients admitted for chest pain observation at a single academic center in Rhode Island.  Over the course of ~2 years, 3,543 patients were admitted for an initial evaluation of chest pain after initial negative cardiac biomarkers in the Emergency Department.  Approximately half of patients underwent stress testing.

Of 1,754 stress tests, there were 29 positives.  Of those, 9 were false positives.  Stratified by pretest probability, none of the patients with a “low probability” Diamond & Forrester Score had a true positive test.  Only 1% of patients admitted and stressed with “intermediate probability” D&F Score ultimately proved to have true positive tests.  Even with “high probability”, 5% of all stress tests performed were true positives.

The author of this article means to specifically reduce stress testing in the “low probability” cohort.  this is a reasonable proposal to skim off a small percentage of tests.  However, he misses asking the better question – how do we reduce use in our “intermediate probability” cohort, which constituted 85% of admissions with just a 1.7% yield for ACS?  We need to seriously address the outdated and inefficient notion admission and testing for these patients is the ideal strategy – and that probably starts by tossing our current guidelines out the window.

“The Association Between Pretest Probability of Coronary Artery Disease and Stress Test Utilization and Outcomes in a Chest Pain Observation Unit”
http://www.ncbi.nlm.nih.gov/pubmed/24730402