Articles That Matter

Pargaonkar VS, Perez MV, Jindal A, Mathur MB, Myers J, Froelicher VF. Long-Term Prognosis of Early Repolarization With J-Wave and QRS Slur Patterns on the Resting Electrocardiogram: A Cohort Study. Ann Intern Med. [Epub ahead of print 27 October 2015]

Benign early repolarization really is benign.


Templin C, Ghadri JR, Diekmann J, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med 2015; 373:929.


Stub D, Smith K, Bernard S, et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation 2015; 131:2143.


Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med 2015; 373:511.


Appelboam A, Reuben A, Mann C, et al. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. Lancet 2015.


Landmark Articles

Bandstein N, Ljung R, Johansson M et al. Undetectable high-sensitivity cardiac troponin T level in the emergency department and risk of myocardial infarction. J Am Coll Cardiol. 2014 Jun 17;63(23):2569-78. doi: 10.1016/j.jacc.2014.03.017. Epub 2014 Mar 30.

CONCLUSIONS: All patients with chest pain who have an initial hs-cTnT level of <5 ng/l and no signs of ischemia on an ECG have a minimal risk of MI or death within 30 days, and can be safely discharged directly from the ED. PMID: 24694529

Comments: Troponin is the preferred biomarker for diagnosis of MI. Can high-sensitivity troponin T be used as part of a rule-out MI protocol?  Of over 14,000 patients in Sweden with chest pain, the NPV for hs-cTnT was 100%, sensitivity 99.8%.  The problem is, these assays are not yet available in the U.S.


Imazio M, Brucato A, Cemin R et al for the ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013 Oct 17;369(16):1522-8. doi: 10.1056/NEJMoa1208536. Epub 2013 Aug 31.

CONCLUSIONS: In patients with acute pericarditis, colchicine, when added to conventional antiinflammatory therapy, significantly reduced the rate of incessant or recurrent pericarditis.

Comments: Colchicine is effective for recurrent pericarditis but what about acute?  Of the 240 patients, those randomized to colchicine 1mg daily for 3 months in addition to usual NSAIDs or steroids had reduced incessant or recurrent pericarditis, "20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group (RR 0.56; 95%CI, 0.30-0.72; NNT = 4; P<0.001).  Of course, colchicine recently went back on a new patent and is very expensive.  Thanks a lot hedge fund manager!


Than M, Cullen L, Aldous S et al. 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. J Am Coll Cardiol. 2012;59(23):2091-8.

CONCLUSIONS: Using the accelerated diagnostic protocol (ADP), a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up. This approach could decrease the observation period required for some patients with chest pain. PMID: 22578923

Comment: Most patients with possible ACS are admitted for longer stays to rule out MI.  Using TIMI score, ECG, and 0 plus 2-hour troponin, can a low-risk cohort be identified for early discharge?  Yes, with a NPV 99.7%.  The major caveat - "Many ADP negative patients had further investigations (74.1%), and therapeutic (18.3%) or procedural (2.0%) interventions during the initial hospital attendance and/or 30-day follow-up."


Van Gelder IC, Groenveld HF, Crijns HJ et al for the RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010 Apr 15;362(15):1363-73. doi: 10.1056/NEJMoa1001337. Epub 2010 Mar 15.

CONCLUSIONS: In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. PMID: 20231232

Comments: Guidelines recommend strict rate control in atrial fibrillation.  614 patients with a-fib were randomly assigned to lenient (<110)  vs. strict (<80) rate control.  "The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events," and was the same in each group.  Ironically, the lenient rate control group was more likely to achieve rate control targets than the strict group.


Quinn J, McDermott D, Stiell I et al. Prospective validation of the San Francisco Syncope Rule to predict patients with serious outcomes. Ann Emerg Med. 2006;47(5):448-54.


Mehta SR, Cannon CP, Fox KA et al. Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA. 2005;293(23):2908-17.


Andersen HR, Nielsen TT, Rasmussen K et al for the DANAMI-2 investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med. 2003;349(8):733-42.

CONCLUSIONS: A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis, provided that the transfer takes two hours or less.

Comment: Lytics for AMI improve outcomes, but would a percutaneous intervention be even better?  For the composite end point of death, clinical evidence of reinfarction, or disabling stroke at 30 days, the PCI group did better - 8.5% PCI vs. 14.2% tPA (P=0.002), NNT = 17.5.  If door to needle time is <120 minutes, PCI is superior.


Wyse DG, Waldo AL, DiMarco JP et al for the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-33.

CONCLUSIONS: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients. PMID: 12466506

Comment: Does it matter which strategy is used in atrial fibrillation as long as both are anticoagulated?  There was a non-significant trend toward increased mortality in the rhythm vs. rate control groups.  There was increased hospitalization and adverse drug events in the rhythm vs. rate control groups as well.  We don't need to be overly concerned about converting all patients to sinus rhythm.


Yusuf S, Zhao F, Mehta SR et al for the CURE Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary
syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494-502.

CONCLUSIONS: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel. PMID: 11519503

Comment: It is known that ASA decreases mortality but what about clopidogrel?  They found that in ~12,500 patients with non-STEMI ACS randomly assigned to ASA or ASA plus clopidogrel 300mg once then 75mg daily vs placebo, the composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke occurred in 9.3% of the patients in the clopidogrel group and 11.4% of the patients in the placebo group (RR 0.80; 95%CI, 0.72-0.90).  Major bleeding was higher in the clopidogrel group, RR 1.38.  Clopidogrel is now commonly used in ACS and STEMI patients in our institution.  


Cohen M, Demers C, Gurfinkel EP et al for the ESSENCE Study Group. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997 Aug 14;337(7):447-52.

CONCLUSIONS: Antithrombotic therapy with enoxaparin plus aspirin was more effective than unfractionated heparin plus aspirin in reducing the incidence of ischemic events in patients with unstable angina or non-Q-wave myocardial infarction in the early phase. This benefit of enoxaparin was achieved with an increase in minor but not in major bleeding.

Comment: LMWH was superior to UFH.  Why our institutional uses UFH still confuses me.


Weigner MJ, Caulfield TA, Danias PG et al. Risk for clinical thromboembolism associated with conversion to sinus rhythm in patients with atrial fibrillation lasting less than 48 hours. Ann Intern Med. 1997;126(8):615-20.


Sgarbossa EB, Pinski SL, Barbagelata A et al. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block. GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators. N Engl J Med. 1996;334(8):481-7.


The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993 Sep 2;329(10):673-82.

 CONCLUSIONS: The findings of this large-scale trial indicate that accelerated t-PA given with intravenous heparin provides a survival benefit over previous standard thrombolytic regimens. PMID: 8204123

Comments: GISSI showed streptokinase was effective in ACS, and ISIS-2 confirmed this.  In TIMI-1, tPA was shown to be better than streptokinase.  In ISIS-3 and GISSI-2, tPA was confirmed to be superior to streptokinase in MI.  GUSTO used a 90 minute tPA infusion vs. 3-hour infusion as in prior studies.  It showed mortality rates of, "streptokinase and subcutaneous heparin, 7.2 percent; streptokinase and intravenous heparin, 7.4 percent; accelerated t-PA and intravenous heparin, 6.3 percent, and the combination of both thrombolytic agents with intravenous heparin, 7.0 percent."  NNT = 91.  More patients had hemorrhagic stroke in the tPA group, NNH = 556.  Lytics for AMI were established with this study only to be later eclipsed by primary PCI, (see DANAMI-2 and this meta-analysis, NNT to save one life = 50.


Lewis HD, Davis JW, Archibald DG et al. Protective Effects of Aspirin against Acute Myocardial Infarction and Death in Men with Unstable Angina -- Results of a Veterans Administration Cooperative Study. N Engl J Med. 1983. 309(7):396-403.

CONCLUSIONS: The principal end points were death and acute myocardial infarction diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms. The incidence of death or acute myocardial infarction was 51% lower in the aspirin group than in the placebo group: 31 patients (5.0%) as compared with 65 (10.1%); P = 0.0005. Nonfatal acute myocardial infarction was 51% lower in the aspirin group: 21 patients (3.4%) as compared with 44 (6.9%); P = 0.005. The reduction in mortality in the aspirin group was also 51%--10 patients (1.6%) as compared with 21 (3.3%)--although it was not statistically significant; P = 0.054. PMID: 6135989

Comment: There was an early understanding that platelet plugs may be responsible for angina and MI.  This RCT with ~1200 veterans, half with placebo and half with ASA 324mg daily, is the reason ASA use is ubiquitous in acute coronary syndromes.

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