Wednesday, August 20, 2014

Does this single lead show a wide complex tachycardia?

A woman in her 50's had a v fib arrest and required defibrillation 10 times before resuscitation to an organized rhythm.

Here was the monitored rhythm:
ventricular tachycardia?








There are two clues that it is not:

1) The rhythm is irregularly irregular, which strongly suggests atrial fibrillation
2) There is a "shelf" on the upslope of the S-wave.  This suggests that it is ST segment, not part of the QRS.

Here is the 12-lead:
Here you can see in leads V4-V6 that the QRS is indeed narrow.  All of the apparent width is really ST segment depression, as well as ST elevation in aVR and V1.

Here I have placed lines to demonstrate the end of the QRS in all leads, using lead II across the bottom for orientation:


After resuscitation, her ECG normalized:


She was found to have an 80% LAD lesion, with open artery and good flow.  This was not definitely a culprit, and not definitely the etiology of arrest.

Lessons:

1. In the presence of ST deviation, the rhythm strip may deceive you into believing there is a wide complex.
2. ST depression is often seen immediately after resuscitation from cardiac arrest.  After a short period of stabilization, it will resolve if there is no underlying acute ischemia

Sunday, August 17, 2014

Middle Aged Male with Burning Chest Pain -- Assess the Entire Clinical Scenario

A middle-aged male presented with “burning” mid chest pain, with radiation to bilateral shoulders (pain radiating to both shoulder is very specific for ischemia).  It started about 5 hours prior to arrival.  He obtained little relief from nitro x 3 by EMS.  There was a history of previous MI, with a stent in the 1st Obtuse Marginal.  He had taken his Plavix for 6 months, then discontinued and also stopped taking his antihypertensives and statin.  He continued to smoke about 1.5 pks per day.

Here is his ECG:
Junctional Bradycardia (this is sinus arrest with junctional escape, and is highly suggestive of ischemia).
  There is a pathologic Q-wave in lead III (old? new?).  
There is slight ST depression in leads I, II, and V3-V6 (fairly specific for ischemia). 
Down-Up T-wave in aVL: very specific for ischemia! 
There are slightly hyperacute T-waves in inferior leads (probable ischemia). 

These are subtle findings.  No single finding is diagnostic of ischemia but he has a very specific combination of factors:

1. typical pain
2. h/o coronary disease
3. pain radiating to both shoulders
4. junctional bradycardia
5. Q-waves
6. ST depression
7. Down-Up T-wave in aVL
7. Possible hyperacute T-waves 

All of these together, but none of them by themselves, diagnose acute MI.

One of my former residents diagnosed this as inferior MI and activated the cath lab.  I love it when my residents become better than I at reading ECGs!

There was a 100% acute occlusion of the RCA, with ischemia of the SA node causing sinus arrest.

Lesson:

1. When highly suggestive ECG signs of ischemia combine with a high pretest probability and refractory ischemic pain, activate the cath lab even if the ECG does not meet STEMI criteria.


Saturday, August 16, 2014

A Very Wide Complex Tachycardia. What is the Rhythm? Use Lewis Leads!!

A patient with a history of severely reduced left ventricular function, renal insufficiency and atrial fibrillation presented with slight dyspnea, without chest pain or syncope.

He had this initial ECG:
There is a very wide, regular, QRS at 250 ms.  There are no P-waves apparent.   There are few isolated conditions which result in this.
What is one?


Here is the patient's previous ECG: 
There is a wide complex with a Left Bundle Branch Block morphology.  There are no P-waves here either, so it appears to be a junctional rhythm.  (The Differential Diagnosis would also include accelerated idioventricular rhythm originating in the right ventricle).  The QRS here also very wide, but not as wide as on the first ECG above.  Notice that the initial r-wave is wider than normal for LBBB.  

Also note that there is notching in the QRS (a "fragmented" QRS), which contributes to the wider-than-normal LBBB [this is Cabrera's sign (a notch on the ascending limb of the S-wave in V3-V5), a fairly reliable sign of previous MI, similar to a Q-wave].  Notice there is also a notch on the descending limb of the S-wave in all inferior leads II, III, aVF.  There is some T-wave Peaking, suggesting hyperkalemia.  

Overall impression of old ECG: Junctional rhythm and peaked T-waves and wide QRS.  This should make you think of hyperkalemia at the time of the old ECG (unfortunately, I don't know if that is the case).

Overall impression of QRS of new ECG: Even worse hyperkalemia superimposed on the conditions present on the old ECG above.  Indeed, the even wider QRS is due to a K of 7.8 mEq/L.  

How about the rhythm on that first ECG?

The patient was diagnosed with Ventricular Tachycardia and given both amiodarone and lidocaine.  I presume the hyperkalemia was treated as well, but do not have that information.  The rate slowed and became irregular, and the QRS narrowed significantly, but the rhythm still could not be discerned (it was still a wide complex).   This ECG is unavailable.

A consulting physician suspected that the underlying rhythm was atrial flutter, and so applied Lewis Leads.

  1. Place the Right Arm electrode on the patient’s manubrium.
  2. Place the Left Arm electrode on the 5th intercostal space, right sternal border.
  3. Place the Left Leg electrode on the right lower costal margin.
  4. Monitor Lead I.
Here is the resulting ECG (limb leads only): 

Perhaps it is better seen here:
Now slow flutter waves (with variable block) are apparent.  They are slow at least partly due to the amiodarone.  Note the axis is different than in the first ECG.  One might be tempted to say "Ahaa!  This different axis is proof that the first ECG was indeed VT!"  But, remember, the Lewis Leads change the axis.  All axis difference is due to lead placement.



The patient was put on hemofiltration to lower the K.  

Diagnosis:

1. Rhythm: Atrial Flutter with 2:1 block, only diagnosed with Lewis leads
2. QRS: Combination of LBBB, old MI and hyperkalemia, all leading to very wide QRS.

LBBB alone seldom has a QRS longer than 200 ms.  See this case of LBBB and hyperK.  

Saturday, August 9, 2014

Poor Microvascular Reperfusion ("No Reflow"): Best Diagnosed by ECG

A previously healthy woman about 50 years old with no previous medical history or coronary risk factors presented 30 minutes after the sudden onset of severe substernal chest pain.  An ECG was recorded and interpreted within 13 minutes:
Sinus rhythm.  Intraventricular conduction delay with a QRS of 117 ms (really, incomplete LBBB)

There are hyperacute T-waves in V4-V6, I and aVL, with reciprocal ST depression and T-wave in version in III and aVF.  V4 shows a de Winter's T-wave, with some ST depression.

  This is diagnostic of proximal LAD occlusion, and I activated the cath lab the moment I saw this ECG. 

We gave clopidogrel 600 mg, aspirin, and a heparin bolus.  There was time to get another ECG, 13 minutes later, before going to the cath lab:
Now there is evolution to ST elevation in V2-V6.
Cath lab results

The patient went to the cath lab and had a door to balloon time of 50 minutes, for a total symptom onset to balloon time of 80 minutes (very fast).  There was complete occlusion of the proximal LAD which was opened and revealed a very large first diagonal (this explains the predominance of V4-V6 on the ECG).   After reperfusion, there was somewhat less "blush" (micovascular reperfusion as demonstrated by slight opacification, by contrast, of the affected myocardium).

There was now TIMI-3 flow, and the patient was pain free, but there was persistent ST elevation in lead V5 on the 6-lead monitor in the cath lab.   Therefore, in addition to thrombectomy, the interventionalist gave intra-coronary adenosine (a vasodilator) to try to improve distal microvascular flow.  As is routine, he also gave intracoronary nitro.  And, of course, he used an eptifibatide bolus and infusion to maximally inhibit platelets.  He did not see any distal "cut off" of vessels in the distribution of the large diagonal or the LAD, but he suspected, based on the persistent ST elevation, that the patient had a significant shower of debris down the diagonal distribution.  He states that "this probably occurred at the time of the acute vessel closure because we did not have any "no flow" or "slow flow" issues that developed acutely during the case."

Here was the post-cath ECG:
Sinus rhythm and a narrower QRS.
 There is persistent ST elevation, and persistently upright T-waves (absence of reperfusion T-waves) in V4-V6.  Though T-waves are inverted in aVL, they are not inverted in lead I, and there is persistent ST elevation in aVL.

After cath, the troponin I was already 107 ng/mL at 5 hours after presentation, and peaked at 178 ng/mL (very large MI).

The patient had a post cath ejection fraction of 36% and persistent chest pain for much of the day.  Due to high risk of cardiogenic shock and dysrhythmia, ICU admission was warranted (usually not necessary for completely successful reperfusion).  

Usually, a low ejection fraction in a patient with rapid restoration of TIMI-3 flow means that the patient has stunned myocardium that will recover.  However, the absence of resolution of ST elevation here is consistent with poor microvascular reperfusion, as is the very high troponin I, and thus recovery of function is not likely to be excellent.

The pain did eventually resolve, but significant damage was done.  For instance, the risk of sudden death from dysrhythmia is much higher than it would have been with good microvascular reperfusion, and she may need to go home on a temporary external automatic defibrillator.

2 days after presentation, here is the ECG:
There is still persistent ST elevation in lateral leads, though now there is T-wave inversion.  There is a new Q-wave in lead I.


No Reflow

This patient had remarkably fast symptom onset to balloon time, and optimal reperfusion therapy, and yet did not get good reperfusion because of poor microvascular reperfusion (thought to be due mostly to downstream microvascular obstruction and/or vasoconstriction).  About 2-5% of patients with successful PCI have no reflow.  Absence of resolution of ST elevation on the ECG is the best indicator of no reflow.   Suffice it to say that these patients have a much worse outcome than patients with good microvascular reperfusion. It's etiology is not uniform for every patient.  It is associated with, among other factors, clopidogrel resistance.  (We usually think of using Prasugrel or Ticagrelor to prevent re-occlusion; maybe we should be using these alternatives to clopidogrel to prevent "no reflow."    The therapy of "No reflow" is based on vasodilators such as adenosine, verapamil, and nitroprusside, as well as on triple antiplatelet therapy; no single mechanical or pharmacologic therapy has proven consistently effective.

Here is one review from 2010.

Here is another review from 2012.

Reperfusion on the ECG: Summary

I will leave the details for the below chapter from my book.

1. The ECG is the best predictor of reperfusion of the microvasculature, even better than angiographic assessment by TIMI flow.  Notice that the interventionalist relied on the ECG to diagnose "no reflow" in this patient.
2. TIMI myocardial perfusion grading (TMP) flows 1-3 grade the amount of microvascular reperfusion seen on angiogram, called "blush".  Absence of microvascular perfusion in the presence of good epicardial blood flow is called "no reflow."
3. "No reflow" is probably mostly caused by downstream showering emboli of platelet aggregates, and also by vasoconstriction.
4.  After reperfusion, the first ECG marker of microvascular reperfusion is T-wave inversion
5.  After reperfusion, the best ECG marker of microvascular reperfusion is resolution of ST segment elevation by at least 50% from maximum, and preferably, > 70% (or complete) resolution.
6.  The ECG is far more reliable at gauging microvascular reperfusion than is resolution of chest pain.



The ECG in REPERFUSION AND REOCCLUSION

This is Chapter 27 (Reperfusion and Reocclusion) from my book, The ECG in Acute MI.  It is long, and has a detailed annotated bibliography.  It comes from literature before 2002, but it is still accurate and almost everything you need to know (unless you are an interventionalist) about the ECG in Reperfusion and Reocclusion.  

Chapter 27:

GENERAL BACKGROUND

Arterial patency and microvascular circulation     
Reperfusion therapy is guided by the ongoing assessment of myocardial reperfusion.  This depends on two factors: 1) reperfusion of the epicardial infarct-related artery (IRA); and 2) reperfusion of the microvascular circulation, which may be damaged by ischemia and reperfusion (the “no-reflow” phenomenon) and result in impeded capillary flow. 
Hemodynamic status and age are the best clinical prognostic indicators for AMI outcome.  The best ECG indicator for AMI outcome is ST resolution or the lack thereof (318-322).  The best overall predictor of failed myocardial reperfusion is a finding of < 50% recovery of ST segments from maximal elevation.  However, the ECG cannot determine whether the cause of failed reperfusion is persistent arterial occlusion or microvascular damage.  Angiography is necessary to assess and grade IRA patency and microvascular circulation and to guide subsequent therapy.  Rescue PCI, which we define as PCI undertaken within 6 hours of the start of thrombolytic therapy, (323) should be strongly considered when clinicians have determined that thrombolytic reperfusion has failed and should be done immediately after transfer to a PCI facility if there is no ECG evidence of good reperfusion (324).  This is especially true for a large AMI, as indicated by anterior location, high ST elevation, or ST deviation in numerous leads.  A patent IRA with inadequate flow may be due to residual stenosis or abnormal microvascular circulation and may be treated with vasodilators, antiplatelet, and antithrombotic agents +/- PCI.

TIMI grading of IRA patency
IRA patency can only be definitively assessed by angiography.  Angiographic assessments are then systematized by TIMI grading, as follows (325): 
·       TIMI-0 = no flow
·       TIMI-1 = penetration of contrast without perfusion.  These patients have persistent ST elevation and a poor prognosis and must be identified for rescue PCI
·       TIMI-2 = partial reperfusion. These patients may have resolution of ST elevation and a prognosis intermediate between TIMI 0/1 and TIMI 3 flow.
·       TIMI-3 = complete reperfusion.  These patients usually (but not always) show ST resolution.  TIMI-3 flow after reperfusion is associated with lower mortality and lower incidence of CHF (326, 327), but its prognostic value may not be independent of resolution of ST elevation (318).
By outcome measures, a flow grade < TIMI-3 indicates failed reperfusion (26, 328).  After reperfusion therapy for AMI, TIMI-3 flow is associated with a 30-42 day mortality of 3.6%, in contrast to TIMI-2 flow (6.6% mortality) and TIMI-0/1 flow (9.5% mortality) (327).
TIMI Frame Count
The TIMI frame count (TFC) further systematizes TIMI flow categorization.  The TFC is the measure of the exact number of cineangiographic frames required for contrast to reach a defined distal segment of the IRA (see Background discussion under Angiographic Reperfusion Grades in the annotated bibliography of this chapter).

TIMI myocardial perfusion grading of microvasculature
TIMI flow and TFC are impacted by both the severity of the underlying stenosis and thrombus and by the microvasculature.  Intact microvasculature is most accurately assessed by the appearance on an angiogram of diffuse and faint highlighting of the myocardium by contrast, known as “myocardial blush.”  These assessments are systematized with TIMI myocardial perfusion grading (TMP), which is based on a scale from 0-3 as follows (319, 326, 329):
·       TMP grade 0 = no microvascular perfusion
·       TMP grade 1 = no clearance of contrast
·       TMP grade 2 = slow clearance of contrast
·       TMP grade 3 = normal clearance.
An open coronary artery may have brisk TIMI-3 flow but have a TMP grade of 0 or 1 (326); patients with these findings show persistent ST elevation (318, 319, 329).  TMP grade 3 is associated with a good prognosis, independent of TIMI flow. 

ECG DIAGNOSIS OF REPERFUSION
ST segments in reperfusion
With a reperfused IRA AND intact microcirculation, ST segments usually fall rapidly and are near baseline within 3 hours of reperfusion (see Case 27-1).  Approximately 80% of cases with IRA reperfusion manifest 50% ST recovery within 90 minutes.  Most of the remaining 20% likely have microvascular injury with resultant poor capillary flow; their prognosis is as poor as patients with poor flow in the IRA (318, 319, 329).  This contrasts with a non-reperfused IRA, in which ST segments fall gradually and plateau, with or without persistent elevation.  Plateauing occurs as early as 6 to 12 hours, due to myocardial cell death (330). 
ST resolution is an accurate predictor of reperfusion, especially in patients whose ECG’s show ST elevation > 4 mm (331).  During or shortly before reperfusion, ST segments often continue to rise before resolving, frequently with an increase in CP (156, 157, 332, 333, 334).  Some patients experience “cyclic reperfusion,” in which there is reperfusion and subsequent reocclusion.  This may occur with or without therapy.  Cyclic reperfusion occurs in 25-30% of AMI before reperfusion therapy and can be detected with ST segment monitoring (335).

T-waves in reperfusion
In reperfused AMI, terminal T-wave inversion often occurs rapidly (within 90 minutes) in the leads that manifested the greatest ST elevation on presentation, and before full ST resolution (156, 157).  This contrasts with non-reperfused AMI, 90% of which show gradual T-wave inversion (over 48 to 72 hours), with a depth < 3 mm (94) (Fig. 8-3).  If there is some myocardial injury, as measured by elevated troponin, expect terminal T-wave inversion to develop into deep and symmetric T-wave inversion over the first 48 hours after the onset of AMI (94) (see Case 27-2). Accordingly, early T-wave inversion (< 24 hours) is associated with greater IRA patency, better perfusion grade, and a more benign in-hospital course than later inversion (336). In some patients with very early reperfusion and very little or no myocardial cell death, as measured by troponin, there may be no T-wave inversion, very late inversion, or reversible inversion (94). 
      Q-wave and R-wave changes are not accurate markers of AMI reperfusion (337).

Reperfusion monitoring
            Monitoring for reperfusion may include observation of 5 elements, as follows: 1) ST resolution, or “recovery;” 2) terminal T-wave inversion; 3) resolution of CP; 4) reperfusion arrhythmias; and 5) biochemical markers. 
1.  ST resolution
ST segment resolution, or “recovery,” is the best marker for reperfusion (see Cases 27-1 and 27-2).  ST segments may be monitored continuously or with static ECG’s every 5 minutes from the time of thrombolytic administration.  If ST elevation is > 4 mm and there is NEITHER  >/= 50% recovery at 60 minutes NOR terminal T-wave inversion, TIMI-3 flow is unlikely.  Strongly consider rescue PCI.
Continuous ST segment monitoring is the best method for monitoring ST segment changes (156, 159, 338, 339) (see Case 27-3).  Commercial products are available.  Select one lead with the greatest ST elevation, plot the ST segment elevation continuously, and observe for peaks and troughs.  By convention, ST elevation is measured on continuous monitors at 80 ms after the J-point.  See Table 27-1.
·       ST recovery >/= 50% from MAXIMAL ST elevation (peak level attained) within 60 minutes and without re-elevation is a very good predictor of reperfusion.  These patients do not need early angiography or rescue PCI.  ST recovery  >/= 50% has a positive predictive value (PPV) for patency (TIMI-2 or -3 flow) of 87%.
·       ST recovery < 50%, consider rescue PCI.  The negative predictive value (NPV) for occlusion (lack of recovery) is 71%; i.e., 71 % of patients who do not show ST recovery >/= 50% have closed arteries and 29% have TIMI 2-3 flow.  These patients are candidates for rescue PCI.  Most importantly, ST recovery < 50% with no terminal T-wave inversion indicates a TIMI flow of 0-2 with a PPV of 86%.  TIMI-3 flow is true successful reperfusion.  Of patients with persistent ST elevation (< 50% recovery), 14% have TIMI-3 flow but presumably continue to have ST elevation due to microvascular injury.
·       The higher the maximal or initial ST elevation, the more accurate the patency prediction (331).
Although static ECG’s are inferior to continuous ST segment monitoring (339), if continuous monitoring is unavailable, recording static ECG’s every 5 minutes from the time of thrombolytic administration is a reasonable substitute (158).  Use the single lead with the highest ST elevation and measure resolution from the maximal height.  ST resolution > 50% at 60 minutes after treatment is a good indicator of reperfusion (158).  Complete ST resolution assures reperfusion but occurs infrequently by 60 minutes after treatment (339).
2.  Terminal T-wave inversion
(See also Chapter 8)
Terminal T-wave inversion within the first 90 minutes is a specific marker of reperfusion and is approximately 60% sensitive (156, 157, 158).  If leads with ST elevation develop terminal T-wave inversion within 60 minutes of thrombolysis, reperfusion is highly likely.  Because T-wave inversion usually indicates some myocardial injury, rapid ST resolution without any T-wave inversion may be evidence that reperfusion occurred before myocardial cell death; in such cases, biomarkers may not be elevated.  Terminal T-wave inversion usually occurs before full resolution of the ST segment.
Deep, symmetric T-wave inversion (> 3 mm) indicates reperfusion that is less recent than reperfusion indicated by terminal T-wave inversion (see Case 27-2).  Terminal T-wave inversion undergoes further development into symmetric T-wave inversion (94).  Deep, symmetric T-wave inversion need not be preceded by ST elevation, although there is usually no development of Q-waves without ST elevation.  Symmetric T-wave inversion is generally present after full resolution of the ST segment.
T-waves also eventually invert in persistently occluded vessels.  T-wave inversion in the presence of deep Q-waves, especially QS-waves, may be a manifestation either of reperfusion late in the course of AMI or of a well-developed, non-reperfused AMI (94, 340).  These inverted T-waves are usually < 3 mm, in contrast with inverted T-waves of reperfused AMI, which are > 3 mm (94).  Such T-wave inversion may be evident at presentation if the patient presents late after onset (see Case 33-3).
With posterior AMI, if the T-wave is upright before reperfusion and there is ST recovery, reperfusion usually results in precordial T-waves (especially V2) becoming fully upright and taller and wider than before AMI onset.  This is a reciprocal view of posterior inverted T-waves.  Reocclusion in this case is unlikely to result in T-wave inversion.  If the T-wave is asymmetrically inverted before reperfusion, reperfusion usually results in T-waves pseudonormalizing (turning upright) and becoming taller and wider than before the onset of AMI; reocclusion generally results in re-inversion of T-waves.  See Case 27-1.  (See also: Cases 16-10 and 13-4).

3.  Relief of Chest Pain
Two studies showed that complete relief of CP, often with an initial transient increase in pain, had a good PPV, with an 84% (339) to 96% (156) chance of reperfusion.  However, relief of CP with neither any recovery of ST segments nor terminal T-wave inversion is unlikely to represent reperfusion.  If CP resolves, record serial ECG’s; pursue rescue angioplasty if there is no ECG evidence of reperfusion.
With spontaneous relief of CP, do not abort reperfusion unless accompanied by some amount of ST recovery:
·       With increased, unchanged, or < 25% ST elevation resolution, continue reperfusion therapy.
·       With 25%-50% resolution, or terminal T-wave inversion, record serial ECG’s or continuous monitoring and look for >/= 50% ST resolution.
·       With 50%-100% resolution, reperfusion therapy may be suspended, pending further assessment, especially continuous ST monitoring.
Relief of CP has a poor NPV, in that persistent pain did not necessarily imply persistent occlusion (159, 339).
4.  Reperfusion arrhythmias
            Occurrence of early accelerated idioventricular rhythm (AIVR) indicates reperfusion with 97% specificity but only 45% sensitivity (335).  A sudden burst of ventricular tachycardia may also indicate reperfusion.
5.  Biochemical markers of reperfusion
Biochemical markers may also be useful in assessing reperfusion; see Chapter 29 for details.

See Cases 27-1 to 27-3 for examples of reperfusion.  (See also: Cases 6-4, 12-3, 16-10, 20-11, and 32-1).
Management
A meta-analysis of randomized trials showed that rescue angioplasty performed in patients with failed reperfusion results in a decreased incidence of CHF, death, and recurrent MI, without significant adverse effects (324).  These trials were performed without the latest technology and with prolonged time intervals from thrombolysis to rescue.  In this age of abciximab and stenting, we highly recommend rapid rescue PCI for failed reperfusion as evidenced by the above-mentioned ECG indicators or by persistent clinical instability.  If TIMI-3 flow is present but TMP grade is low, treatment with vasodilators, antiplatelet, and antithrombotic agents is particularly important.

REOCCLUSION
Once reperfusion is achieved, monitor ST segments for reocclusion.  Symptoms are not reliable indicators of reocclusion and many recurrent AMI’s are asymptomatic (69, 89).  If continuous monitoring is unavailable, record frequent static ECG’s every 30 to 60 minutes until stability is assured.  At a minimum, record hourly ECG’s for several hours after reperfusion.
ECG manifestations of reocclusion
Each AMI has an “ischemic fingerprint,” such that reocclusion of the same vessel at the same location reproduces the same ECG findings (83, 190).  Thus, reocclusion manifests the reverse of reperfusion on the ECG, as follows:
·       Initial rapid “pseudonormalization” of T-waves, in which inverted T-waves turn upright.
·       Subsequent re-elevation of ST segments.
Caution: post-infarction regional pericarditis (PIRP) may mimic reocclusion (see Chapter 28) (94).  This is characterized by gradual pseudonormalization of T-waves or persistent upright T-waves in the leads that had the greatest ST elevation at presentation.  There is also gradual ST re-elevation, over 24-72 hours.  PIRP lacks the typical diffuse ST elevation of nonspecific pericarditis. 
See Case 27-3 of reocclusion.  (See also: Case 8-12, of pseudonormalization of symmetrically inverted T-waves; Case 13-4 of an inferoposterior AMI with reperfusion and reocclusion; and Case 3-3 of reocclusion a week after reperfusion).

Management
Reocclusion after thrombolysis mandates either repeat thrombolysis or, preferably, rescue angiography +/- PCI. 

ANNOTATED BIBLIOGRAPHY

Reperfusion: General background

Krucoff MW et al., Continuously updated 12-lead ST-segment recovery analysis for myocardial infarct artery patency assessment and its correlation with multiple simultaneous early angiographic observations, 1993.  
Methods:  Krucoff et al. (341) performed angiography and continuous ST segment monitoring in 22 AMI patients. 
Findings:  Forty-four episodes of arterial patency and multiple ST trend transitions in 11 of 22 patients after thrombolysis suggested cyclic changes in coronary flow before catheterization. 
Comment:  These authors and others (158, 159) have shown repeatedly that ST recovery must be measured from maximal ST elevation for accurate assessment of reperfusion.  Peak ST elevation may occur in the absence of or any time after thrombolytic therapy.  Static ECG’s are less effective than continuous monitoring because ST segments may rise from baseline before actual reperfusion and fall again (or vice versa) to nearly the same level without detection.

Angiographic reperfusion grades, persistent ST elevation, and prognosis

Background: TIMI flow grade is a measurement of reperfusion of a coronary vessel and TMP flow grade is a measurement of myocardial microvascular perfusion.  TFC is the measure of the exact number of cineangiographic frames required for contrast to reach a defined distal segment of the IRA. TFC is especially helpful to further categorize TIMI-2 and TIMI-3 flow.  Normal mean TFC’s are: 36.2 +/- 2.6 for the LAD, 20.4 +/- 3.0 for the RCA, and 22.2 +/- 4.1 for the circumflex artery (342).  To standardize TFC for all arteries, the TFC of the LAD is divided by 1.7 to give a “corrected” TFC (CTFC) (342).  At 90 minutes after thrombolysis for STEMI in all locations. a CTFC of 0-13 is above normal blood flow and is associated with mortality of 0%.  A CTFC of 14-40 is associated with mortality of 2.7%, and a CTFC > 40 is associated with mortality of 6.4% (343).  Of patients with TIMI-3 flow, CTFC </= 20 vs. > 20 is associated with complication rates of 7.9% vs. 15.5%, respectively (343).  

 

Van’t Hof et al., Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction, 1998. 
Methods:  Van ‘t Hof et al. (320) studied ST resolution in 403 AMI patients with TIMI-3 flow after primary angioplasty.
Findings:  ST segments normalized in 51% of patients (ST < 0.1 mV).  Partial normalization (30-70% of initial height) was associated with a relative risk (RR) of death of 3.6 (CI =  1.6-8.3) compared with full normalization(< 30% of initial height).  Absence of resolution or increased ST elevation was associated with a RR of death of 8.7 (range = 3.7-20.1).

Van’t Hof et al., Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade, 1998.  
Methods:  Van ‘t Hof et al. (329) studied myocardial blush during primary angioplasty in 777 AMI patients. 
Findings:  Angioplasty resulted in TIMI-3 flow in 89% of patients and in TIMI-0, -1, or -2 flow in 11%.  Patients with TMP grades 3, 2, and 0/1 had:  1) CK infarct sizes of 757 IU/L, 1143 IU/L, and 1623 IU/L; 2) EF’s of 50%, 46%, and 39%; and 3) mortality (after a mean follow-up of 1.9 +/- 1.7 years) of 3%, 6%, and 23%, respectively.  TMP grade predicted mortality independently of Killip class, TIMI grade flow, EF, and other clinical variables.  TMP grade was the best predictor of 3-year mortality, with rates of 3%, 15%, and 37% for patients with grades 3 (19% of patients), 2, and 0/1, respectively.  Among TMP grade 3 patients, ST elevation normalized in 65% and ST elevation decreased in an additional 28%.

Gibson CM et al., Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs, 2000. 
Methods:  Gibson et al. (326) studied 762 patients in the TIMI-10B trial, in which 854 patients with AMI were randomized to TNK-tPA or standard alteplase and underwent angiography at 90 minutes post-thrombolytic administration.
Findings:  TMP grade 3 myocardial perfusion was independently associated with low 30-day mortality of 2.0%, as compared to 3.5% for patients with TIMI-3 flow.  The decreased risk was additive to the low risk of TIMI-3 flow, such that mortality was a mere 0.73% (1 of 137) for patients with TIMI-3 flow and TMP grade 3 perfusion compared to a 10.9% mortality (14 of 129) for those with both TIMI 0-2 and TMP 0/1 grading.   Mortality was approximately the same for patients with: (1) both TIMI 0-2 flow and TMP grade 3 perfusion, presumably through collaterals; and (2) both TIMI-3 flow and TMP 0/1 perfusion.

ST recovery and prognosis

ST recovery can be a good prognostic indicator, even in the presence of an occluded vessel.  Lack of ST recovery portends a poor prognosis, even with an open artery.
Claeys MJ, Determinants and prognostic implications of persistent ST-segment elevation after primary angioplasty for acute myocardial infarction: importance of microvascular reperfusion injury on clinical outcome, 1999. 
Methods:  Claeys et al. (319) studied 91 AMI patients with reperfusion after angioplasty. 
Findings:   Of 91 patients, 75 had TIMI-3 and 16 had TIMI-2 flow.  Persistent ST elevation, defined as ST >/= 50% of the initial height, was observed in 33 (36%) patients and was associated with high one-year mortality (15% vs. 2%) and high total major adverse cardiac event rate (45% vs. 15%).  Persistent ST elevation was the most important independent determinant of major adverse cardiac event rate, with an adjusted RR of 3.4, and both were attributed to impaired microvascular circulation.

Shah A et al., Prognostic implications of TIMI flow grade in the infarct related artery compared with continuous 12-lead ST-segment resolution analysis.  Reexamining the "gold standard” for myocardial reperfusion treatment, 2000. 
Methods:  Shah et al. (318) identified 258 AMI patients who underwent thrombolysis and then angiography in the TIMI-7 and GUSTO-1 trials (see Appendix).  Patients were stratified according to TIMI 0-3 reperfusion and by ST resolution >/= 50% vs. < 50%. 
Findings:  ST resolution WAS an independent predictor of the combined clinical outcome of death or CHF but TIMI flow grade was NOT.  ST resolution among patients with TIMI grade 0-1 flow identified a group with a relatively benign clinical course.

Dissman R et al., Early assessment of outcome by ST segment analysis after thrombolytic therapy in acute myocardial infarction, 1994. 
Methods:  Dissman et al. (321) studied CK levels and EF’s in 77 AMI patients to correlate ST resolution and infarct size. 
Findings:  The enzyme-determined infarct size and the resulting EF correlated closely with complete (>70%), partial (30-70%), or no ST (<30 3="" 43="" 53="" 58="" and="" at="" complete="" ef="" for="" hours="" nbsp="" no="" o:p="" or="" partial="" patients="" post-thrombolysis.="" resolution="" respectively.="" s="" were="" with="">

Schroder R et al., Extent of early ST segment elevation resolution: a strong predictor of outcome in patients with acute myocardial infarction and a sensitive measure to compare thrombolytic regimens, 1995.  
Methods:  Schroder et al. (322) analyzed ECG’s, CK levels, and mortality data of 1909 AMI patients randomized to reteplase or SK. 
Findings:  In 1398 patients who presented </= 6 hours from AMI onset, 35-day mortality rates for complete (>/= 70%), partial (30-70 %), or no (< 30%) ST resolution by 3 hours post-thrombolytic administration were 2.5%, 4.3%, and 17.5%, respectively.

Saran RK et al., Reduction in ST segment elevation after thrombolysis predicts either coronary reperfusion or preservation of left ventricular function, 1990. 
Methods:  Saran et al. (344) studied ST segment changes and angiographic findings in 45 patients (see more detailed annotation below).
Findings:  LV function was well-preserved if the ST segment had fallen by >/= 25% at 3 hours.

Continuous ECG monitoring for prediction of reperfusion

Note:  It is important to remember when evaluating the following studies that 15% of IRA’s are open without treatment by 6-8 hours post-coronary occlusion (345).
Krucoff MW et al., Continuous 12-lead ST-segment recovery analysis in the TAMI 7 study.  Performance of a non-invasive method for real-time detection of failed myocardial reperfusion, 1993. 
Methods:  Krucoff et al. (159) tested a method of 12-lead continuous ST segment recovery in a blinded, prospective, and angiographically correlated study of 144 TAMI-7 patients who received thrombolytics in early MI.  Summated ST elevation was plotted against time by PC-based software and read by experienced cardiologists.  The ST segment was plotted and assessed for peaks, troughs, and general trend.  The ST score at the moment of angiography was compared to the peak elevation attained.  Patency was predicted based on ST recovery, defined as a 50% drop from the maximum summated ST elevation, and continued downward trend.   Occlusion was predicted by (1) persistent ST elevation, (2) re-elevation after recovery or a downward trend, or (3) increased ST elevation.  The study was considered indeterminate if no definite peaks or troughs and corresponding trends could be discerned. 
Findings:  There were 144 ST segment analyses.  Of 35 angiograms performed during definite (re-) elevation periods (indicating occlusion), 25 IRA’s were angiographically occluded.  Of 91 angiograms during definite recovery periods (indicating reperfusion), 81 IRA’s were angiographically patent.  Of 18 indeterminate analyses, 14 were angiographically patent.  If the indeterminate group is considered to be “probably not occluded,” then the IRA was patent in 95 of 109 cases (87%) so predicted and occluded in 25 of 35 cases (71%) so predicted.  Of 35 patients whose ST recovery analysis determined IRA’s to be “occluded” (based on persistent or recurrent ST elevation), only 5 had TIMI-3 flow.  In 109 patients, analysis determined “probably not occluded,” (“indeterminate” or “patent”) and 73 of these had TIMI-3 flow, 22 had TIMI-2 flow, and 14 had TIMI-0 or 1 flow.  Thus, “occluded” had a PPV for TIMI 0-2 flow of 86% and “probably not occluded” had a sensitivity of 94% and a PPV of 67% for TIMI-3 flow and of 87% for TIMI-2 or -3 flow.  
Comment:  Post-thrombolytic TIMI-3 flow is associated with a much better outcome than even TIMI-2 flow (26, 328).  Therefore, the ability to distinguish TIMI-3 flow from TIMI-0 to -2 flow on the ECG is important.

Klootwijk P et al., Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial, 1996. 
Methods:  Klootwijk et al. (331) studied ECG’s of 373 GUSTO-1 patients (see Appendix) using continuous 12-lead ST segment recovery analysis.
 Findings:  The predictive values for reperfusion or persistent occlusion were not as good as in the study of Krucoff et al. described above (159).  Angiograms were performed significantly later (between 90-180 minutes) in this study.  Thus, the predictive accuracy would be expected to be lower because ST segments in areas of persistent infarction decline over time, due to myocardial cell death.  A decrease of >/= 50% from peak and no persistent re-elevation before angiography was used as a prediction of “patent.” Accuracy was very high (79-100%) in patients with high ST elevation (> 4 mm).  In 116 patients with a peak ST elevation >/= 4 mm, a prediction of “patent” had a PPV of 79% and NPV of 75%.

Doevendans PA et al., Electrocardiographic diagnosis of reperfusion during thrombolytic therapy in acute myocardial infarction, 1995. 
Methods:  Doevendans et al. (156) performed continuous ST segment monitoring of 61 AMI patients for 60 minutes after thrombolytic therapy. 
Findings:  Reperfusion was associated with rapid ST resolution, often after a transient elevation.  Of 44 patients with reperfusion, 42 showed >/= 25% decrease in ST elevation from maximal height (sensitivity 95%), but only one of 17 patients without reperfusion showed this amount of normalization (specificity 94%).  Using a 50% decrease in ST elevation as a cutoff, sensitivity was 85% (38 of 44 patients) and specificity was, again, 94%.  Relief of CP was also a very sensitive sign of reperfusion; 25 of 26 patients with reperfusion had relief within 1 hour.  Eighteen patients experienced relief after a transient, often marked, increase in pain.  Terminal T-wave inversion was very specific for reperfusion; 28 of 44 patients with reperfusion had terminal T-wave inversion, whereas only 1 of 17 without reperfusion had terminal T-wave inversion.  AIVR was a specific but insensitive marker of reperfusion; 16 of 42 in the reperfused group demonstrated AIVR vs. one of 17 in the nonreperfused group.  Other “reperfusion arrhythmias” were uncommon and of little prognostic utility.  CK-MB peaked earlier in the reperfused group.

Veldkamp RF et al., Comparison of continuous ST-segment recovery analysis with methods using static electrocardiograms for noninvasive patency assessment during acute myocardial infarction, 1994. 
Methods:  Veldkamp et al. (346) analyzed ECG’s and clinical data from 82 patients in the above study by Krucoff et al. (159) to compare continuous ST recovery analysis with 5 static methods. 
Findings:  Static methods such as those used by Saran et al. (344), Hackworthy et al. (347), and Clemmensen et al. (348) had comparable accuracies to continuous ST recovery analysis; see section below on static ECG’s.

Hohnloser SH et al., Assessment of coronary artery patency after thrombolytic therapy: accurate prediction using the combined analysis of three noninvasive markers, 1991.
Methods:  Hohnloser et al. (338) used Holter monitoring and angiography in a prospective study of 82 patients undergoing thrombolysis for first MI. 
Findings:  Of 82 patients, 63 had TIMI-2 or -3 reperfusion.  A 50% reduction in ST elevation measured 60 to 90 minutes after thrombolysis had a PPV of 97% and an NPV of 43% for reperfusion.  CK peak < 12 hours was an accurate marker of reperfusion.

Frequent static ECG’s

Shah PK et al., Angiographic validation of bedside markers of reperfusion, 1993
Methods:  Shah et al. (158) obtained static ECG’s every 5-10 minutes after thrombolytic therapy in 82 AMI patients, for up to 3 hours, until angiography. 
Findings:  Their findings were very similar to those of Doevendans et al. (156) described above.  Angiography demonstrated that 69 of 82 patients had a patent IRA with TIMI-3 flow and that these patients consistently manifested a rapid, progressive decrease in both CP and ST elevation.  Pain resolved in 24 +/- 23 minutes (maximum 50 minutes) and decreased ST elevation >/= 50% occurred within 16 +/- 14 minutes (maximum 41 minutes) after restoration of TIMI-3 flow.  Terminal T-wave inversion and AIVR were also specific but insensitive markers of reperfusion.  This study demonstrates the importance of frequent static ECG’s and the insensitivity of using only 2 static ECG’s to detect reperfusion.  In 58% of patients, ST segments were unstable, rising and falling, before final resolution.

Infrequent static ECG’s

Califf RM et al., Failure of simple clinical measurements to predict perfusion status after intravenous thrombolysis, 1988. 
Methods:  Califf et al. (339) performed angiography on 386 TAMI patients at 60 and 90 minutes post-administration of tissue plasminogen activator (tPA).  They recorded a baseline ECG and another at 90 minutes post-tPA, before the 90-minute coronary injection. 
Findings:  They found no sensitive AND specific marker of reperfusion using infrequent static ECG’s.  Complete resolution of ST segment and T-wave changes was associated with a 96% IRA patency rate at 90 minutes post-tPA, but this occurred in only 6% of patients.  Only 38% of patients had “partial resolution” of ST segments, 84% of whom showed reperfusion.  Complete resolution of CP occurred in 29%, of whom 84% had reperfusion of the IRA.  Unchanged or worsened CP occurred in 20%, of whom 60% showed reperfusion.  Patent IRA’s were demonstrated in 56% of patients with neither symptom nor ST resolution and 63% of patients with no change in ST segments showed reperfusion.  Although arrhythmias occurred frequently during the first 90 minutes of therapy, none were associated with a higher patency rate.

Saran RK et al., Reduction in ST segment elevation after thrombolysis predicts either coronary reperfusion or preservation of left ventricular function, 1990. 
Methods:  Saran et al. (344) performed angiography on 45 AMI patients by 3 hours post-administration of anistreplase.
 Findings:  Using the lead with the greatest ST elevation on static ECG’s, ST recovery  >/= 25% at 3 hours was nonspecific.  ST segments had fallen by >/= 25% in 30 of 31 patients with TIMI-2 or -3 reperfusion, but also in 8 of 14 patients who had only TIMI-0 or -1 flow.  Thus, if the ST segment fell by >/= 25%, the specificity was only 43%; that is, many IRA’s remained occluded.  Three hours post-thrombolytic therapy is too late for ST recovery to be a meaningful indication of reperfusion because ST segments fall gradually, even in persistently infarcted myocardium.  It is also too late to make a decision for rescue PCI.  If the ST segment fell by < 25%, persistent occlusion was likely, with a PPV of 86%.  Importantly, the global EF was well maintained in patients whose ST segments fell > 25% and whose arteries were occluded.  Saran et al. concluded that a reduction in ST elevation of > 25% within 3 hours of thrombolysis indicates either a patent IRA or preservation of LV function. 

Clemmensen P et al., Changes in standard electrocardiographic ST-segment elevation predictive of successful reperfusion in acute myocardial infarction, 1990. 
Methods:  Clemmensen et al. (348) studied 53 patients up to 8 hours post-SK administration.  They calculated the ST score as the sum of ST elevation in 11 leads, based on static ECG’s obtained within 5 minutes of angiography. 
Findings:  Angiography demonstrated reperfusion (TIMI-2 or -3 flow) in 33 of 53 patients.  A decrease of >/= 20% in ST elevation was 88% sensitive and 80% specific for reperfusion, with a PPV of 88% and an NPV of 80%.  Clemmensen et al. concluded that a decrease of only 20% in the ST score following thrombolytic therapy is a useful and noninvasive predictor of reperfusion status in patients with evolving AMI. 
Comment:  The use of angiographic patency assessment up to 8 hours post-treatment diminishes the value of this data.  

 

T-wave inversion and prognosis

See also Doevendans et al. (156) above.
Oliva PB et al., Electrocardiographic diagnosis of postinfarction regional pericarditis: ancillary observations regarding the effect of reperfusion on the rapidity and amplitude of T wave inversion after acute myocardial infarction, 1993. 
Methods:  Oliva et al. (94) studied 200 AMI patients to assess serial T-wave changes as prognostic indicators. 
Findings:  Ninety percent of patients with reperfusion demonstrated a maximum T-wave negativity of >/= 3 mm in the lead that initially showed the greatest ST elevation within 48 hours of CP onset.  Seventy-six percent of patients with no reperfusion demonstrated a maximum T-wave negativity of </= 2 mm within 72 hours.  Oliva et al. conclude that rapid evolution and deepening of the T-wave may be useful noninvasive markers of reperfusion.

Matetzky S et al., Early T wave inversion after thrombolytic therapy predicts better coronary perfusion: clinical and angiographic study, 1994. 
Methods:  Matetzky (336) et al. performed admission and pre-discharge angiography and radionuclide ventriculography on 94 consecutive AMI patients who received tPA.
Findings:  Early T-wave inversion (< 24 hours) was associated with greater IRA patency, better perfusion grade, and a more benign in-hospital course.  Additionally, although the number of patients with normal EF’s (>55%) at presentation was similar, 71% of patients with early T-wave inversion had a normal EF at discharge, vs. 44% of patients without early T-wave inversion.

Increased pain and ST elevation post-thrombolytic therapy

Dissman R et al., Sudden increase of the ST segment elevation at a time of reperfusion predicts extensive infarcts in patients with intravenous thrombolysis, 1993. 
Methods:  Dissman et al. (332) measured ST elevation and CK every 15 minutes after thrombolytic administration in 61 AMI patients. 
Findings:  Eight patients showed increased ST elevation immediately after reperfusion.  This was associated with an enzymatically very large AMI, a very early enzyme peak, and much worse LV EF (39% +/- 14 vs. 58% +/- 11, p < 0.0005).  Six patients also experienced very clearly intensified CP at the time of the ST elevation.  The study by Doevendans et al. (156) described above and a study by Wehrens et al. (157) both found a similar increase in CP after treatment and before ECG evidence of reperfusion.

Reciprocal depression and reperfusion

Shah A et al., Comparative prognostic significance of simultaneous versus independent resolution of ST segment depression relative to ST segment elevation during acute myocardial infarction, 1997. 
Methods:  Shah et al. (143) performed continuous ST segment monitoring of 413 AMI patients who received thrombolytics; 261 patients met technical criteria for blinded analysis of ST depression resolution patterns.  
Findings:  In-hospital mortality was 13% among patients whose reciprocal ST depression persisted after resolution of ST elevation vs. 1% mortality for patients whose ST elevation and ST depression resolved simultaneously.

Reperfusion arrhythmias

Although there is little literature to support malignant reperfusion ventricular arrhythmias, many interventionalists and clinicians who treat AMI are certain that runs of ventricular tachycardia are directly related to opening the IRA, especially in large infarcts that are reperfused very early. 

Gorgels AP et al., Usefulness of the accelerated idioventricular rhythm as a marker for myocardial necrosis and reperfusion during thrombolytic therapy in acute myocardial infarction, 1988 and Goldberg S et al., Limitation of infarct size with thrombolytic agents: electrocardiographic indexes, 1983 and Miller FC et al., Ventricular arrhythmias during reperfusion, 1986.  
Methods:  Gorgels et al. (349) and Goldberg et al. (350) were among the first to describe “reperfusion arrhythmias.” Gorgels et al. prospectively studied 87 patients admitted with ischemic CP and Goldberg et al. studied 44 AMI patients who underwent angiography.  Miller et al. (351) conducted Holter monitoring of 52 patients.
Findings:  Gorgels et al. found AIVR in 27 of 70 AMI patients with reperfusion.  Goldberg et al. found some type of reperfusion arrhythmia, most commonly AIVR, in 20 of 27 AMI patients with reperfusion.  Miller et al. found no significant relationship of either AIVR or ventricular tachycardia with reperfusion or persistent occlusion.

Hohnloser SH et al., Assessment of coronary artery patency after thrombolytic therapy: accurate prediction using the combined analysis of three noninvasive markers, 1991.
Methods:  Hohnloser et al. (338) prospectively studied 82 first AMI patients treated with thrombolytics.  
Findings:  AIVR was associated with reperfusion only in inferior AMI.

Shah PK et al., Angiographic validation of bedside markers of reperfusion, 1993.  
Findings:  Shah et al. (158) (described above) found that 49% of patients with reperfusion developed AIVR.

Gore JM et al., Arrhythmias in the assessment of coronary artery reperfusion following thrombolytic therapy, 1988.  
Methods:  Gore et al. (352) performed angiography within 8 hours of symptom onset in 67 AMI patients treated with thrombolytics. 
Findings:   Fifty-six patients had total IRA occlusion, 25 of whom reperfused within 90 minutes of treatment.  Arrhythmias (including AIVR) were not significantly associated with reperfusion.

Gressin V et al., Holter recording of ventricular arrhythmias during intravenous thrombolysis for acute myocardial infarction, 1992. 
Methods:  Gressin et al. (353) performed 24-hour Holter monitoring of 40 AMI patients treated with thrombolytics. 
Findings:  Increased incidence of AIVR was associated with IRA patency.

Clements IP, The electrocardiogram in acute myocardial infarction, 1998. 
Findings:  Clements (335) cites a thesis by Veldkamp, who combined analysis from 6 studies (317 patients) and found that early AIVR predicted patency with a specificity of 97% but a sensitivity of only 45%.

Vectorcardiography

Dellborg M et al., Dynamic QRS complex and ST segment vectorcardiographic monitoring can identify vessel patency in patients with acute myocardial infarction treated with reperfusion therapy, 1991. 
Findings:  Dellborg et al. (354) identified 15 of 16 patients with reperfusion and 5 of 6 with persistent occlusion using vectorcardiographic analysis of ST vectors.  Further detail is beyond the scope of this book.  See Clements (335) for an excellent discussion of alternative electrocardiographic methods such as vectorcardiography and precordial mapping.  See also von Essen et al. (355) and Badir et al. (356) for vectorcardiographic analyses of reperfusion. 

Rescue PCI

Ross AM et al., Rescue angioplasty after failed thrombolysis: technical and clinical outcomes in a large thrombolysis trial, 1998.  
Methods:  Ross et al. (323) analyzed GUSTO-1 (see Appendix) data on rescue angioplasty, defined as angioplasty undertaken within 6 hours of the start of thrombolytic therapy.  They compared 198 patients selected non-randomly for rescue angioplasty, 226 patients with failed thrombolysis who were managed conservatively, and 1058 patients with successful thrombolysis. 
Findings:  Patients with rescue angioplasty had more impaired LV function prior to intervention.  Rescue was successful in 88.4% of occluded arteries, resulting in TIMI-3 flow in 68%.  Successful rescue angioplasty was associated with better LV function and lower mortality than conservative management of occluded arteries.  Neither bleeding complications (8.6% vs. 6.8%) nor the need for CABG (1.0% vs. 0.4%) differed significantly between the 2 groups.

Ellis SG et al., Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction, 1994.
Methods:  Ellis et al. (357) randomized 151 patients with first anterior AMI and failed thrombolysis, as determined by angiography done within 8 hours after treatment, to angioplasty or to conservative management. 
Findings:  Angioplasty performed at a mean of 4.5 +/- 1.9 hours after thrombolytic therapy was successful in 72 of 78 (92%) patients.  Outcomes in the angioplasty vs. conservatively managed groups, respectively, were death in 5% vs. 10% (P = 0.18), severe heart failure in 1% vs. 7% (P = 0.11), and either death or severe heart failure in 6% vs. 17% (P = 0.05).  LV function at rest did not differ. 

McKendall GR et al., Value of rescue percutaneous transluminal coronary angioplasty following unsuccessful thrombolytic therapy in patients with acute myocardial infarction, 1995. 
Methods:  McKendall et al. (358) studied 133 patients enrolled in TIMI Phase I Open Label and Phase II trials; 100 had received no rescue angioplasty and 33 patients had undergone rescue angioplasty by protocol (not by physician choice) if the 90-minute angiogram revealed persistent IRA occlusion. 
Findings:  Time to angioplasty from symptom onset or from thrombolytic treatment is not stated, but appears to be 90 to 120 minutes.  The two groups had similar baseline features.  Rescue was technically successful in 26 of 33 patients (82%).  Mortality at 21 days was 12% in the rescue group and 7% in the no-rescue group (p=NS).  Failed rescue was associated with a mortality of 33%.  Mean LV EF was the same in both groups.

CORAMI Study Group, Outcome of attempted rescue coronary angioplasty after failed thrombolysis for acute myocardial infarction, 1994. 
Methods:  The CORAMI Study Group (359) evaluated short and mid-term outcomes of 299 consecutive AMI patients who received thrombolytics < 6 hours after symptom onset and underwent angiography at 90 minutes post-thrombolytics. 
Findings:  Of 299 patients, 87 (29%) had failed thrombolysis (TIMI-0 to -1 flow), of whom 72 underwent rescue angioplasty within 8 hours of symptom onset.  Seven patients (10%) were in cardiogenic shock at the time of angiography.  Technical success (TIMI-3 flow) was achieved in 65 patients (90%) at a mean of 300 +/- 101 minutes after thrombolytic therapy.    Nine patients (12%) had access site hematoma.  Three patients (4%) died, 2 of 65 successful rescues and 1 of 7 failed rescues.

Gibson C et al., Rescue angioplasty in the Thrombolysis in Myocardial Infarction (TIMI) 4 trial, 1997. 
Methods:  Gibson et al. (360) studied 95 AMI patients with failed thrombolysis (TIMI 0-1 flow) in the TIMI-4 trial. 
Findings:  Fifty-eight patients underwent rescue angioplasty 120 minutes post-thrombolytic therapy and 37 had no rescue angioplasty.  Rescue and non-rescue groups had similar baseline characteristics.  Fifty-two of 58 procedures were successful.  In-hospital adverse outcomes, including death, recurrent AMI, severe CHF, cardiogenic shock, and EF < 40%, occurred in 35% of rescue cases (29% of successful rescues and 83% of failed rescues, p = 0.01), and also in 35% of non-rescue cases (p = NS).

Miller JM et al., Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial), 1999. 
Methods:  Miller et al (361) prospectively studied 392 patients entered into the GUSTO-III trial (reteplase vs. tPA for STEMI) (362) who underwent rescue angioplasty in a nonrandomized fashion; 83 patients received abciximab and 309 did not.
Findings:  When adjusted for baseline differences, patients who received abciximab had significantly lower mortality.  Incidence of severe bleeding (without ICH), with vs. without the use of abciximab during angioplasty was 3.5% vs. 1.0% (p = 0.08).

Ellis SG et al., Review of immediate angioplasty after fibrinolytic therapy for acute myocardial infarction, 2000. 
Methods: Ellis et al. (324) performed a meta-analysis of 9 heterogeneous randomized trials of rescue angioplasty (1456 patients).  
Findings:  Rescue angioplasty decreased the incidence of CHF, death, and recurrent MI.

In summary, although the value of rescue PCI makes intuitive and scientific sense, the available studies are too small and the methodology inadequate for definite conclusions.  All of the studies had a minimum delay of 2 hours and a mean delay of 4-5 hours between thrombolytic therapy and balloon inflation.  None used up-to-date technique including stents, abciximab, and/or clopidogrel.  We recommend rescue PCI for large infarctions with no ECG evidence of reperfusion at one hour post-thrombolytic therapy unless and until there are studies that take these factors into account and demonstrate lack of efficacy.
 
Reocclusion
Langer A et al., Prognostic significance of ST segment shift early after resolution of ST elevation in patients with myocardial infarction treated with thrombolytic therapy: the GUSTO-I ST Segment Monitoring Substudy, 1998. 
Methods:  Langer et al. (363) performed ST segment monitoring within 30 minutes of thrombolytic therapy in 734 AMI patients.
Findings:  “ST segment shift,” defined as elevation of >/= 1 mm in the 6-24 hours after reperfusion, was correlated with 7.8% mortality at 30 days and 10.3% mortality at 1 year vs. 2.3% and 5.7% mortality respectively for patients without ST shift.

Ohman EM et al., Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction, 1991. 
Methods:  Ohman et al. (89) studied 810 AMI patients who had angiography performed 90 minutes post-thrombolytic therapy. 
Findings:  Reperfusion occurred acutely in 735 patients, 645 of whom (88%) underwent angiography 7 days later.  IRA REocclusion occurred in 91 patients (14%) and was symptomatic in 53.  Reocclusion was associated with greater in-hospital mortality (11% vs. 4.5%), a more complicated hospital course, and initial angiographic findings including RCA stenosis, a greater degree of stenosis, and lower TIMI flow grade.

Dissman R et al., Early recurrence of ST-segment elevation in patients with initial reperfusion during thrombolytic therapy: impact on in-hospital reinfarction and long-term vessel patency, 1994. 
Methods:  Dissman et al. (364) performed 24-hour Holter monitoring on 81 AMI patients.
Findings:  ST resolution within the first 4 hours occurred in 67 patients (83%), 31 of whom (46%, Group 1a) did have subsequent ST re-elevations and 36 of whom (54%, Group 1b) did not.  Group 1a had a much greater incidence of CK-MB-confirmed re-infarction (26% vs. 6%) and angiographic occlusion at follow-up (40% vs. 17%) than Group 1b.

Veldkamp RF et al., Performance of an automated real-time ST segment analysis program to detect coronary occlusion and reperfusion, 1996. 
Methods:  Veldkamp et al. (212) used an automated real-time ST segment analysis program to detect reocclusion during 78 balloon occlusions in 31 patients. 
Findings:  The program detected balloon reocclusion and reperfusion within seconds of all occlusions that caused a peak ST elevation >/= 0.2 mV.

Krucoff MW et al., Stability of multilead ST-segment "fingerprints" over time after percutaneous transluminal coronary angioplasty and its usefulness in detecting reocclusion, 1988. 
Methods:  Krucoff et al. (190) analyzed multi-lead ST segment recordings performed during angioplasty in 39 patients. 

Findings:  Similar to Bush et al. (83) described above, within one hour, balloon occlusion during repeat angioplasty resulted in an identical “ischemic fingerprint” 90% of the time.  AMI of the same vessel within 24 hours of the balloon inflation resulted in this ischemic fingerprint 87% of the time.  Thus, reocclusion reliably produces the initial ECG pattern of infarction.  Monitoring for reocclusion can be done using continuous ST segment monitoring.

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