Good critique of the paper - you are quite right, Adrian, it suffers predominantly from being a post-hoc analysis.

Only other paper I could lay my hands on is a myocardium salvage study, in which they note that patients without chest pain still demonstrate myocardial salvage using Tech scanning, though the authors note that chest pain severity is, unsurprisingly, still important. (Abstract follows, as does comment by Olson.)  Can debate the outcome importance of myocardial salvage, but I think is important for CCF development, which would be in keeping with the retrospective 1994 Cox paper.

The advice from our local cardiologists is to perform thrombolysis where the patient has had a convincing history of cardiac pain but is presently pain free (obviously with ST elevation).

Anton

J Am Coll Cardiol 1993 Nov 1;22(5):1311-6

Severity and response of chest pain during thrombolytic therapy for acute myocardial infarction: a useful indicator of myocardial salvage and infarct size.

Christian TF, Gibbons RJ, Hopfenspirger MR, Gersh BJ.

Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.

OBJECTIVES. The purpose of this study was to determine noninvasively whether chest pain severity is predictive of the amount of myocardium at risk and whether the response of pain during thrombolysis is associated with myocardial salvage during acute myocardial infarction. BACKGROUND. The perception of chest pain and response to reperfusion therapy during acute myocardial infarction may provide important information for treatment benefit. Previous studies have been limited by the inability to measure myocardium at risk and myocardial salvage. METHODS. Sixty-two patients with acute myocardial infarction received an injection of technetium-99m sestamibi before thrombolysis and again at hospital discharge. Tomographic imaging was performed 1 to 6 h later. Myocardium at risk, infarct size and absolute myocardial salvage were derived from these images using previously described techniques and were expressed as a percent of the left ventricle. Salvage index was calculated by divid!
ing myocardial salvage by the myocardium at risk. Chest pain severity was graded before thrombolysis as none, mild, moderate or severe. Chest pain response during thrombolytic therapy was graded as none, partial or completely resolved. RESULTS. There was no association between chest pain severity and myocardium at risk, but there was a weak trend toward greater myocardial salvage and salvage index (p = 0.09 and p = 0.12, respectively) for patients with more severe symptoms. Patients without chest pain at the start of thrombolysis still demonstrated significant salvage (11 +/- 11% of the left ventricle, p = 0.009). There was a significant association between chest pain response to therapy and both myocardial salvage (p = 0.03) and salvage index (p = 0.01). By multivariate analysis, chest pain severity and response of chest pain during thrombolysis were significant independent predictors of myocardial salvage, salvage index and infarct size. Thrombolysis was most effective in !
the 20 patients (32%) with moderate or severe chest pain and !
complete resolution of symptoms during thrombolysis (salvage of 79% to 89% of the area at risk). In the remaining 32 patients with chest pain, salvage of the area at risk was only 32%. CONCLUSIONS. These findings suggest that the assessment of chest pain before and after thrombolytic therapy is a readily available, useful indicator of the efficacy of the therapy.


J Am Coll Cardiol 1993 Nov 1;22(5):1317-9

Comment on:
J Am Coll Cardiol. 1993 Nov 1;22(5):1311-6.

Bedside cardiology and thrombolysis.

Olson HG.

The study by Christian et al. (37) provides useful clinical information for the management of the patient with myocardial infarction with thrombolytic therapy. 1) Complete resolution of chest pain during the infusion of an intravenous thrombolytic agent suggests reperfusion and myocardial salvage. Initial conservative medical management should be considered in these patients especially if serial ECGs show a progressive and rapid downward defection of the ST segment. 2) Patients presenting within 6 h after the onset of infarction, who are pain free, may still benefit from thrombolysis if their ECGs show persistent ischemia. 3) In the remaining patients in whom chest pain does not resolve completely during thrombolytic therapy, management, whether continued medical or invasive strategy, should be individualized and dictated by the extent of myocardium at risk (i.e., by the number of ECG leads showing ST segment elevation), the response of the ST segment to thrombolysis and, mo!
st important, the clinical status of the patient.

In message <002701c2e5d9$c2227fe0$e177fea9@mydell> Adrian Fogarty <[log in to unmask]> writes:
> But this was a retrospective and uncontrolled study Anton, i.e. the painfree
> patients were ALL thrombolysed, so you can't draw any conclusions about what
> would have happened had they not been thrombolysed, which is the crux of the
> original question from Phil Munro. You have misinterpreted, or rather
> misapplied the findings of this paper to Phil's patient, but this is clearly
> not applicable. The only way to "prove" your point would be to divide the
> 337 painfree patients into thrombolyse or non-thrombolyse and then compare
> outcomes; this paper did not do that.
>
> Basically this paper fails to demonstrate that the painfree patients would
> not have ended up with good ejection fractions (or less risk of failure etc)
> had they not received thrombolysis in the first place, as we just don't know
> this because they all were given thrombolysis from the outset. My hypothesis
> (the null hypothesis) is that these patients would have fared just as well,
> perhaps better, without thrombolysis, but this paper does not test this
> hypothesis so it cannot be relied upon.
>
> Adrian Fogarty
>
>
> ----- Original Message -----
> From: <[log in to unmask]>
> To: <[log in to unmask]>
> Sent: Saturday, March 08, 2003 9:32 PM
> Subject: Re: Thrombolysis Question
>
>
> > Phil,
> >
> > Would still thrombolyse - these patients seem to develop less CCF than
> their peers with chest pain at the time of thrombolysis, otherwise similar
> in other respects. (Abstract follows)
> >
> > Anton
> >
> > Am J Cardiol 1994 Apr 15;73(11):729-36
> >
> > Effect on outcome of the presence or absence of chest pain at initiation
> of recombinant tissue plasminogen activator therapy in acute myocardial
> infarction. The Thrombolysis in Myocardial Infarction Investigators.
> >
> > Cox DA, Rogers WJ, Aguirre FV, Forman S, Solomon R, Zaret BL.
> >
> > University of Alabama Medical Center, Birmingham 35294.
> >
> > To ascertain whether the outcome of patients with suspected myocardial
> infarction differs when chest pain is still present at initiation of
> thrombolytic therapy, participants in the Thrombolysis in Myocardial
> Infarction Phase II study, all of whom presented within 4 hours of symptoms
> onset, were retrospectively divided into 2 groups: (1) those with chest pain
> present at onset of intravenous thrombolysis, n = 3,000; and (2) those who
> were free of chest pain on beginning intravenous thrombolytic therapy, n =
> 337. Patients free of chest pain were older (58 vs 57 years, p = 0.01), more
> often women (23 vs 17%, p = 0.01), had fewer electrocardiographic leads with
> ST elevation (3.8 vs 4.1, p < 0.001), and the presenting event was confirmed
> less often as myocardial infarction than as chest pain without infarction
> (88 vs 96%, p < 0.001). There were no significant differences between the 2
> groups for in-hospital death, reinfarction, recurrent ischemic events,
> stroke, overall hemorrhag!
> > ic complications, coronary angioplasty or bypass surgery. At 6-weeks
> follow-up, more pain-free patients had resting ejection fraction > 0.55 (35
> vs 31%, p = 0.001) and fewer developed congestive heart failure (12 vs 20%).
> At 1-year follow-up, fewer pain-free patients developed congestive heart
> failure (15 vs 21%, p = 0.009), but no differences existed between the 2
> groups in frequency of death, reinfarction, coronary angioplasty, bypass
> surgery or anginal class. Thus, there are several observations in patients
> who were free of chest pain at onset of lytic therapy. (1) The majority
> developed enzymatic or electrocardiographic evidence of acute myocardial
> infarction.