Category: Cardiology

All Elevated Troponins Are Not MI

Have you ever received sign-out on a patient, heparinized, awaiting cardiology consultation – and later, at your leisure, realized the troponin level just barely tips into positive territory and probably has nothing to do with acute coronary syndrome?

I know you have.

This is the cardiology “expert consensus” on interpretation of troponin elevations – 25 pages of clinical summary and 360 references worth of dissecting what an elevated troponin really means.  There’s an hour-long lecture worth giving based on this publication.

The key portions include:
 – Figure 1, which is a nice conceptual overview in which elevated troponins are separated into their “ACS” and “non-ACS” categories.
 – Section 6, which discusses the possible role (if any) for troponins in non-ischemic conditions.
 – Appendix 4, the clinical conditions in which positive troponins are non-cardiac and confounding in origin.

Positive troponins need to be evaluated properly in their clinical context, and this is a lovely (if very, very long) reference document for describing it.

“ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations”
www.ncbi.nlm.nih.gov/pubmed/23154053

The Hazards of Love

“Sexual activity is mechanically dangerous, potentially infectious and stressful for the cardiovascular system.”

Indeed!

According to this retrospective review of 11 years of electronic health records from University Hospital Bern, Switzerland, they identified 445 patients seeking emergency care secondary to sexual intercourse.  The majority of emergency department visits were secondary to suspected infectious etiologies (62%), but neurologic complaints, trauma, and cardiovascular incidents comprised the remaining portion.  

The trauma portion probably speaks for itself without need for additional detail.  There was one myocardial infarction and one aortic dissection.  Among the “various complaints”, two patients were diagnosed with “eczema”.  However, among the neurologic emergencies, there were 12 cases of subarachnoid hemorrhage and 11 cases of – ah – “transient global amnesia”.

All things being equal, at least, sexual activity was only associated with 0.1% of emergency department visits – hardly the most dangerous of potential choices of recreation.

“Sexual activity-related emergency department admissions: eleven years of experience at a Swiss university hospital” 
http://www.ncbi.nlm.nih.gov/pubmed/23100321

Arrhythmogenic Right Ventricular Dysplasia

In young Emergency Department patients with syncope, most of the time, testing is minimal.  Generally, the only universal testing is a pregnancy test and/or an electrocardiogram.

We’ve gotten pretty good at understanding the “life-threatening” causes of syncope in young adults diagnosed by electrocardiography, including:
 – Wolff-Parkinson-White Syndrome
 – Hypertrophic Obstructive Cardiomyopathy
 – Brugada Syndrome
 – Congenital Long QT

But there’s always more, and Arrhythmogenic Right Ventricular Dysplasia is one of those “more” that seems not to be on everyone’s lists.  ARVD is a genetically-inherited abnormality in cardiac desmosomes that leads to fibrofatty deposition in the right ventricle.  It is currently estimated to result in ~5% of the sudden cardiac deaths in adults under age 65, secondary to sustained monomorphic ventricular tachycardia.  The characteristic EKG finding to look out for is, unfortunately, quite subtle – the “epsilon wave”.  These waves are most prominent in V1-V3, and manifest as sharp upward deflections from baseline at the conclusion of the QRS complex.

Very few Emergency Department presentations mix the high-risk needle-in-the-haystack with the low-risk like young adults with syncope, so it’s important to stay alert for these rare ECG findings.

“Impact of new electrocardiographic criteria in arrhythmogenic cardiomyopathy”
www.ncbi.nlm.nih.gov/pubmed/23015790

Still Overpromising Benefit of PCI After Cardiac Arrest

The folks in France have been promoting PCI universally after cardiac arrest for quite some time.  It’s an appealing concept – when you look at subgroups of out-of-hospital cardiac arrest, there’s a significant portion of folks who clearly have a primary cardiac cause, and clearly will benefit from emergency or early PCI.

However, this study inappropriately tries to make the case for all patients to receive PCI and therapeutic hypothermia after out-of-hospital cardiac arrest.  This is a retrospective, cohort study spanning eight years of resuscitation, coordinated between Paris, France and Seattle, Washington.  They used vital records follow-up to determine patient status for each OHCA patient surviving to hospital discharge, and then looked for associations between survival and whether they received PCI or hypothermia in-house.  The most absurd statement is as follows:

“A beneficial survival association was evident among those with and without ST-elevation MI. This finding is provocative given the current debate about whether patients without evidence of ST elevation following resuscitation can benefit from PCI and should undergo early and routine coronary catheterization.”

Retrospective studies such as this suffer from substantial selection bias, in which the patients who are selected for particular therapies have interactions and confounders that simply cannot be controlled or adjusted.  Patients benefit from PCI when they have a disease process amenable to intervention – and this is clearly not every cardiac arrest patient. The patients in this study who received PCI – and hypothermia – likely had specific features that identified them to treating physicians as candidates to benefit from these therapies.

The reasonable conclusion from the data presented is exactly that – cardiac arrest patients that have specific features that make them candidate for these therapies will benefit.  PCI following cardiac arrest should not be considered to be “routine”.

“Long-Term Prognosis Following Resuscitation From Out of Hospital Cardiac Arrest – Role of Percutaneous Coronary Intervention and Therapeutic Hypothermia” 

When Cardiologists Risk-Stratify Heart Failure

This is the “MARKED” score, a multi-marker prognostic risk score derived from emergency department patients presenting with acute dyspnea.  The authors state they’ve presented a “simple, straightforward” score that “may help the treating physician at the ED to decide on urge of intervention, admission, and timing of re-evaluation.”

Sounds perfect!  A valuable tool to determine which patients are at high-risk for short-term mortality, possibly to predict which patients may have unanticipated poor outcomes if discharged home?

Ah, sadly, no.

When these cardiologists risk-stratify heart failure, they’re using 90-day mortality – an endpoint almost certainly irrelevant to acute evaluation of dyspnea.  The authors recognize the “single-center” aspect of their study as a limitation – but, considering this comes from a dedicated “cardiology ED” in Holland, the external validity is extraordinarily limited.  The authors also do not offer any practical suggestion regarding how this score might be used in practice – or how decision-making using this score effectively changes outcomes compared with usual care.

Finally, this “simple” score features the commonly used laboratory tests such as NT-proBNP, high-sensitivty cardiac troponin T, Cystatin-C, high-sensitivity C-reactive protein, and Galectin-3.  It should be no surprise a few authors receive compensation from Roche Diagnostics and ACS Biomarker B.V.

“Multimarker Strategy for Short-Term Risk Assessment in Patients With Dyspnea in the Emergency Department”
www.ncbi.nlm.nih.gov/pubmed/23021334

The End of IABP?

Adding to the “don’t do anything, just stand there!” file, another relatively frequently used cardiovascular support tool – intra-aortic balloon counterpulsation – might be on the chopping block.

Typically used in cases of severe cardiogenic shock secondary to acute myocardial infarction, IABP is used to reduce strain on the stunned myocardium.  The first IABP-SHOCK pilot of 45 patients showed no mortality difference, but a significant improvement in BNP levels with IABP use.  This is the follow-up study, enrolling 600 patients to IABP or best available medical therapy.

Both groups were similarly ill – the IABP group had 6% more anterior STEMIs – and had nearly identical outcomes.  There were 1.5% more survivors in the IABP group, but the p value was 0.69.  Adverse events were similar – although the control group tended towards increased sepsis, which seems a little odd.  There was an expected random assortment of subgroups favoring one therapy or another, but nothing that would seem to be specifically hypothesis generating.

In the end, the authors rather grimly state that, despite some surrogate markers appearing to be improved in the IABP group, there is no evidence to support routine use of IABP in cardiogenic shock secondary to acute myocardial infarction.

“Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock”
http://www.nejm.org/doi/full/10.1056/NEJMoa1208410

FFR(CT) – So Close, Yet So Far

As David Newman will tell you, the additive prognostic and predictive value for stress tests is fairly weak.  CT coronary angiograms are still a test looking for the correct population.  Conventional coronary angiography is expensive, invasive, and clearly not appropriate for the massive population of low risk patients we evaluate.

So, how about a non-invasive test that combines three-dimensional anatomic coronary reconstruction with predictive flow dynamics to identify lesions resulting in ischemia?  This test is CT coronary angiography combined with computed fractional flow reserve.  And, it would be a beautiful thing if it were ready for primetime – but it’s not.

I’ve reviewed a previous trial of FFR(CT).  This is a larger study, published in JAMA, of 285 patients with suspected CAD who underwent CCTA with FFR(CT), followed by conventional coronary angiography with invasive FFR measurement.  Figure 1 summarizes the results relatively succinctly – but essentially, 56 of the 172 FFR(CT) patients with lesions calculated as ischemic were false positives.  On the flip side, 67 of the 80 FFR(CT) patients with lesions calculated as non-ischemic were false negatives.  The per-vessel performance of FFR(CT) basically added no additional diagnostic AUC to CT alone.

The study is sponsed by HeartFlow, and authored by several physicians disclosing conflicts of interest with diagnostic imaging manufacturers.  Unsurprisingly, the authors try to spin the positive out of it in their conclusions and abstract.

“Diagnostic Accuracy of Fractional Flow Reserve From Anatomic CT Angiography“
http://jama.jamanetwork.com/article.aspx?articleid=1352969

How Fast Can We Rule-Out AMI?

Six hours?  Two hours?  One hour?  McDonalds’ drive-thru?

This is the paper from Archives of Internal Medicine that’s been making the rounds in the lay press regarding how quickly the ER should be able to detect your AMI with the new highly-sensitive troponins.  This is the APACE, prospective, international, multi-center study evaluating patients with “symptoms suggestive of acute myocardial infarction” and onset within the last 12 hours.

In this cohort, 1247 patients were recruited – and >300 were excluded for either going straight to the cath lab or having “another procedure performed” at the 1-hour time mark – and received hs-cTnT at index, 1, 2, 3, and 6 hours after presentation.  Myocardial necrosis was defined as a hs-cTnT >99th percentile, which for this assay is 14 ng/L, and a diagnosis of acute MI was made by two independent cardiologists upon review of records and lab results.

The authors split their cohort into two groups, a derivation cohort and a validation cohort, and did some statistical wrangling to come up with two cut-off strategies – one for rule-in and one for rule-out.  They were able to make diagnostic decisions on ~76% of their cohort at the one-hour time point, and 52 ng/L at presentation or an increase within an hour of 5 ng/L or more was ~94% specific for AMI.  Likewise, 12 ng/L and an increase less than 3 ng/L at 1 hour was ~100% sensitive for AMI.  The remaining 25% of their cohort was in a non-diagnostic zone.  At 30 days, there was one death in their rule-out cohort, for a 99.8% survival rate.

So, can you use this strategy?  If you feel as though this study is externally valid to your populations and you’re using the same Roche Diagnostics test, you certainly may.  Every piece of data is something you can incorporate to your discussions with a patient regarding diagnostic certainty and risk.  Even an extra hour occupying an ED bed rather than moving out to a chest pain observation facility can significantly impede ED flow, while observation admissions are costly and inconvenient to patients.  The ideal strategy will depend on the capabilities of individual departments.

This study, along with the primary author, are sponsored in part by Abbott, Roche, and Siemens.
www.ncbi.nlm.nih.gov/pubmed/22892889

Vancouver Chest Pain Rule in Tehran

Iran and Canada would be considered by most to be very different places.  However, from a cardiovascular standpoint, it seems they’re not so disparate.


This is a prospective, validation study of the Vancouver Chest Pain Rule.  The Vancouver rule is one of many 2-hour accelerated rule-outs operating under the presumption that all disease can never be detected – sensitivity will never be 100%, but this assumes a context in which a discussion may be had with the patient about outpatient disposition.  Essentially, any patient under 40 years without a history of coronary artery disease and a normal EKG simply gets discharged.  Older than 40 and atypical chest pain is discharged either immediately after a CK-MB < 3.0 µg/L, or receives a 2-hour delta + repeat EKG if > 3.0 µg/L.  Essentially, the rule is designed only to ensure all unusual NSTEMIs are picked up.


In the initial study, the 30-day ACS rate for the discharged group was 1.2%.  In this Iranian study, the 30-day ACS rate of 292 very-low-risk patients is 1.3%.  Two of the four patients meeting criteria for discharge by CK-MB had positive troponins.  Considering CK-MB is nearly considered anachronistic now, most modern EDs would have not have discharged these patients based on troponin testing.  A third patient had EKG changes on the second EKG – which should fail the Vancouver rule, so I’m uncertain why it was included in their very-low-risk group.  Finally, the last patient had an entirely normal evaluation and a subsequent 70% lesion discovered on angiography a week later.  No mention of the hemodynamic significance/relation to ischemia of this lesion is noted.


A few hundred patients is hardly a definitive validation, but it’s a nice demonstration that 50% of their cohort could have been discharged in two hours – and with the same 30-day event rate as the poor people being made to glow in the CCTA studies.


“Validation of the Vancouver Chest Pain Rule: A Prospective Cohort Study”