Perfusion after AMI

Leonardo Bolognese, Giampaolo Cerisano
Division of Cardiology, Careggi Hospital, Florence, Italy
Correspondence: Dr Leonardo Bolognese, Division of Cardiology, Careggi Hospital, Florence, Italy.
Tel: +39 0554277221, fax: +39 0554277625, e-mail: carddept@tin.it

Introduction
A case is presented of a 62-year-old man with acute myocardial infarction successfully treated by means of primary coronary angioplasty of the culprit vessel. A myocardial contrast echocardiography (MCE) study was performed during infarct-related artery occlusion, shortly after PTCA, and 48 h afterwards to assess microvascular status after optimal recanalization of the epicardial vessel.
Early MCE showed an evident contrast enhancement in the infarct area associated with a brisk epicardial flow (using conventional contrast dye angiographic assessment) indicating tissue level reperfusion. However, late MCE study at 48 h showed, in spite of the persistence of a brisk epicardial flow, the absence of a significant contrast effect in the infarct area after injecting the bubbles (sonicated contrast dye) in the infarct-related vessel, indicating an extensive microvascular obstruction.
The subsequent course was uneventful and a mild regional and global functional recovery was observed at the predischarge echocardiographic study and the calculated ejection fraction (EF) was 45%. Repeat echocardiography 1 month after the index infarction revealed a dilated, poorly contracting left ventricle and an EF of 25%.
This case illustrates the dynamic behavior of microvascular status after acute myocardial infarction and highlights the importance of optimal and sustained tissue reperfusion for preserving left ventricular geometry. In fact, despite restoration of epicardial blood flow, early or late microvascular obstruction may negatively influence left ventricular remodeling after reperfusion.

Case report
The patient was a 62-year-old male with a history of hypertension who presented to the emergency department of our hospital complaining of severe and persistent chest pain lasting about 2 h.
On admission, the patient was slightly tachypnoic. Heart rate was 98 bpm and blood pressure 115/70 mm Hg. Heart sounds were normal and at the apex a soft protomesosystolic murmur was audible, compatible with mitral regurgitation. Rales were audible over the bases of the lungs.
The ECG on admission showed marked ST-segment elevation in leads V1–V5 compatible with acute anterior infarction. There were also mild repolarization abnormalities in the inferior leads.
The echocardiogram showed severe left ventricular regional motion abnormalities (akinesia) involving the anterior wall, anterior septum, and apex, and a moderate left ventricular dysfunction (EF 38%). The left ventricular enddiastolic and endsystolic dimensions were 51 and 40 mm, respectively. There was a mild mitral regurgitation.
Due to the short time elapsed from the onset of symptoms and the extension of the area at risk, the patient was commenced on intravenous infusion of heparin and abciximab and promptly transferred to the catheterization laboratory for emergency coronary angiography and primary coronary angioplasty if suitable. Coronary angiography revealed the occlusion of the midportion of the left anterior descending (LAD) coronary artery after the first diagonal branch (Figure 1).

Figure 1. Left: Coronary angiography; right: myocardial contrast echocardiogram (long axis view) in a patient with acute anterior myocardial infarction before recanalization. The angiogram shows occlusion of LAD in the mid portion after the first diagonal branch. Myocardial contrast echocardiogram reveals the absence of opacification in the medium segment of the septum and apex (area at risk).

MCE was performed (by injecting 3 mL hand-agitated iopamidol) during coronary occlusion and revealed the absence of contrast effect in the medium segment of the septum and apex (area at risk) (Figure 1). A successful (TIMI flow grade 3 and residual stenosis <30%) PTCA and stenting of the LAD were performed (Figure 2).

Figure 2. Repeat myocardial contrast echocardiogram shortly after successful primary PTCA of the LAD (left) shows an homogeneous contrast enhancement of the risk area (right).

Repeat MCE, shortly after infarct-related artery recanalization, showed an homogeneous contrast enhancement of the risk area (Figure 2).
After primary PTCA the patient remained asymptomatic and was transferred to the coronary care unit where intravenous infusion of abciximab and low-dose heparin was continued for 12 h and oral antiplatelet (aspirin 300 mg/day and ticlopidin 500 mg/day) and ACE inhibitor therapy was instituted. Creatine phosphokinase peaked at 2357 IU/L after 7 h from onset of acute myocardial infarction.
During the first 48 h after primary PTCA the patient recovered quickly. There were neither recurrent ischemic episodes nor significant arrhythmias, and no rales were subsequently heard; no signs of congestion were seen on chest x-ray and his ECG showed a progressive disappearance of ST-segment shift with T waves becoming negative in the infarct leads. Repeat MCE at 48 h showed the absence of a significant contrast enhancement in the risk area despite the persistence of a brisk epicardial flow (TIMI 3) at coronary angiography (Figure 3).

Figure 3. Forty-eight hrs follow-up coronary angio-graphy (left) showing the persistence of an optimal epicardial patency. Myocardial contrast echocardiogram (right) revealing the disappearance of a significant contrast enhancement in the risk area.

Predischarge (day 5) echocardiogram showed a mild regional and global functional recovery and the calculated EF was 45%.
Four weeks after discharge the patient started to complain of dyspnea on intensive exercise. Again, repeat coronary angiography revealed the persistence of LAD patency, but 2-D echocardiography showed a dilated, poorly contracting left ventricle and EF was 25%
(Figure 4).

Figure 4. Four weeks after discharge repeat coronary angio demonstrates the presistence of LAD patency (left) but 2D-Echo (four chamber view) shows a dilated, poorly contracting left ventricle (right).

Discussion
In acute myocardial infarction early restoration of anterograde flow can limit the progression of myocardial necrosis and should enhance the functional recovery of postischemic dysfunctioning myocardium, improving left ventricular function and geometry, and early and late survival.[1] However, the adequacy of reperfusion depends not only on persistent patency of the infarct-related artery but also on the integrity of distal circulation. Embolization of plaque contents of platelet thrombus or platelet aggregation in the microcirculation with loss of endothelial integrity may compromise the recovery of perfusion at tissue level. Until recently, we have had limited access to diagnosing microvascular obstruction in patients with acute myocardial infarction. With the availability of imaging technology, such as MCE, microvascular dysfunction after optimal recanalization of the epicardial vessel has been documented in a far greater proportion of patients than was previously thought possible.
The link between microvascular dysfunction and unfavorable clinical outcome has been documented in many studies.[2–4] Thus, MCE performed in the catheterization laboratory during the acute phase of myocardial infarction, looking beyond epicardial coronary patency, may identify higher risk patients with microvascular dysfunction.
The mechanism of microvascular dysfunction after optimal recanalization of the infarct-related artery is not completely understood. Duration of ischemia and time to recanalization are the most powerful determinants of microvascular dysfunction. However, the amount of tissue perfusion in infarcted patients is dependent on many other complex and interrelated factors including extent of collateral circulation, residual stenosis, extent of reperfusion injury, and loading conditions. This may explain some recent results showing progressive microvascular obstruction within the infarcted territory beyond coronary reflow up to 48 h,[5] supporting the hypothesis that microvascular damage might be caused by mechanisms activated after coronary artery reflow,[6] and not only during the occlusion period.[7] On the other hand, some recent studies have also shown that microvascular dysfunction may improve over time, indicating that microvascular impairment is not always irreversible.[8] Thus, microvascular dysfunction is a dynamic process. In this regard, the case reported is paradigmatic. Serial MCE, performed shortly after recanalization and at 48 h from the index infarction, showed a clear reversal of initial microvascular reflow, despite persistent patency of the infarct-related artery. There are two potential alternative explanations for this behavior. (1) Because of hyperemia during the early hours of reperfusion, MCE may have underestimated the infarct size and overestimated the myocardial salvage. This may be particularly true when the residual stenosis is not severe enough to attenuate hyperemic flow, as in the present case. (2) After initial reflow an extensive reperfusion injury might have induced a late and progressive microvascular obstruction. Whatever the truth may be, this case highlights the issue of the appropriate timing of microvascular assessment after reperfusion. Sakuyama et al[9] reported that most of the changes in the distal circulation occur by day 1 after recanalization of the infarct-related artery, and that microvascular assessment 2 days after recanalization better predicts early and late clinical events. Thus, a very early MCE assessment of microvascular status may foster the ‘illusion of reperfusion’.
Finally, the second important message arising from this case is that microvascular dysfunction complicating mechanical reperfusion has clinical and prognostic consequences. Patients with microvascular dysfunction by MCE demonstrate progressive ventricular dilatation, as opposed to the reduction in ventricular volume seen in patients with restored microvascular perfusion.[10] They also have more clinical events at follow-up compared with patients who achieved restoration of normal microvascular flow.[10] Thus, microvascular status after restoration of epicardial flow may be the missing link between reperfusion, left ventricular function and geometry, and clinical outcome in acute myocardial infarction.

REFERENCES 

1: Circulation 1993 Jul;88(1):296-306

Related Articles, Books, LinkOut

2: Circulation 1992 May;85(5):1699-705

Related Articles, Books, LinkOut

Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction.

Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP, Blumenthal RS, Lima JA.

Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md, USA.

BACKGROUND: The extent of microvascular obstruction during acute coronary occlusion may determine the eventual magnitude of myocardial damage and thus, patient prognosis after infarction. By contrast-enhanced MRI, regions of profound microvascular obstruction at the infarct core are hypoenhanced and correspond to greater myocardial damage acutely. We investigated whether profound microvascular obstruction after infarction predicts 2-year cardiovascular morbidity and mortality. METHODS AND RESULTS: Forty-four patients underwent MRI 10 +/- 6 days after infarction. Microvascular obstruction was defined as hypoenhancement seen 1 to 2 minutes after contrast injection. Infarct size was assessed as percent left ventricular mass hyperenhanced 5 to 10 minutes after contrast. Patients were followed clinically for 16 +/- 5 months. Seventeen patients returned 6 months after infarction for repeat MRI. Patients with microvascular obstruction (n = 11) had more cardiovascular events than those without (45% versus 9%; P=.016). In fact, microvascular status predicted occurrence of cardiovascular complications (chi2 = 6.46, P<.01). The risk of adverse events increased with infarct extent (30%, 43%, and 71% for small [n = 10], midsized [n = 14], and large [n = 14] infarcts, P<.05). Even after infarct size was controlled for, the presence of microvascular obstruction remained a prognostic marker of postinfarction complications (chi2 = 5.17, P<.05). Among those returning for follow-up imaging, the presence of microvascular obstruction was associated with fibrous scar formation (chi2 = 10.0, P<.01) and left ventricular remodeling (P<.05). CONCLUSIONS: After infarction, MRI-determined microvascular obstruction predicts more frequent cardiovascular complications. In addition, infarct size determined by MRI also relates directly to long-term prognosis in patients with acute myocardial infarction. Moreover, microvascular status remains a strong prognostic marker even after control for infarct size.

PMID: 9498540 [PubMed - indexed for MEDLINE]

Early predictors of left ventricular remodeling after acute myocardial infarction.

Bolognese L, Cerisano G.

Division of Cardiology, Careggi Hospital, Viale Morgagni, Florence, Italy.

Ventricular remodeling after acute myocardial infarction is characterized by alteration in left ventricular (LV) size, shape, and wall thickness and involves both the infarcted and the noninfarcted regions of the ventricle. These structural changes are the result of several distinct pathologic processes that contribute to progressive LV dilation: rearrangement of wall structure, myocyte hypertrophy, and increasing muscle mass without an increase in wall thickness (eccentric hypertrophy). The pathogenesis of LV remodeling is multifactorial. Multiple factors may in fact contribute at different stages from the time of coronary occlusion until the development of ventricular dilation: These include the magnitude of the loss of contractile elements, the abrupt alteration in systolic and diastolic loading conditions, the activation of circulating neurohormones and local autocrine trophic factors, and the patency of the infarct-related artery. Although remodeling occurring early after infarction may be an appropriate compensatory response to preserve ventricular function, recent observations have suggested that this long process has a deleterious effect on LV function and prognosis. Thus attempts to inhibit these structural changes have been the focus of recent experimental and clinical studies. This review focuses on interactive factors that influence postinfarction LV remodeling, emphasizing the role of some new emerging determinants such as the extent of surviving myocardium within the infarcted and noninfarcted zones.

Publication Types:

• Review
• Review, Tutorial

PMID: 10426864 [PubMed - indexed for MEDLINE]

5: Circulation 1998 Sep 8;98(10):1006-14

Related Articles, Books, LinkOut

Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction.

Rochitte CE, Lima JA, Bluemke DA, Reeder SB, McVeigh ER, Furuta T, Becker LC, Melin JA.

Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.

BACKGROUND: Microvascular obstruction within an area of myocardial infarction indicates worse functional recovery and a higher risk of postinfarction complications. After prolonged coronary occlusion, contrast-enhanced MRI identifies myocardial infarction as a hyperenhanced region containing a hypoenhanced core. Because the time course of microvascular obstruction after infarction/reperfusion is unknown, we examined whether microvascular obstruction reaches its full extent shortly after reperfusion or shows significant progression over the following 2 days. METHODS AND RESULTS: Seven dogs underwent 90-minute balloon occlusion of the left anterior descending coronary artery (LAD) followed by reflow. Gadolinium-DTPA-enhanced MRI performed at 2, 6, and 48 hours after reperfusion was compared with radioactive microsphere blood flow (MBF) measurements and myocardial staining to define microvascular obstruction (thioflavin S) and infarct size (triphenyltetrazolium chloride, TTC). The MRI hypoenhanced region increased 3-fold during 48 hours after reperfusion (3.2+/-1.8%, 6.7+/-4.4%, and 9.9+/-3.2% of left ventricular mass at 2, 6, and 48 hours, respectively, P<0.03) and correlated well with microvascular obstruction (MBF <50% of remote region, r=0.99 and thioflavin S, r=0.93). MRI hyperenhancement also increased (21.7+/-4.0%, 24.3+/-4.6%, and 28.8+/-5.1% at 2, 6, and 48 hours, P<0.006) and correlated well with infarct size by TTC (r=0.92). The microvascular obstruction/infarct size ratio increased from 13.0+/-4.8% to 22.6+/-8.9% and to 30.4+/-4.2% over 48 hours (P=0.024). CONCLUSION: The extent of microvascular obstruction and the infarct size increase significantly over the first 48 hours after myocardial infarction. These results are consistent with progressive microvascular and myocardial injury well beyond coronary occlusion and reflow.

PMID: 9737521 [PubMed - indexed for MEDLINE]

7: J Clin Invest 1974 Dec;54(6):1496-508

Related Articles, Books, LinkOut

Early changes in myocardial perfusion patterns after myocardial infarction: relation with contractile reserve and functional recovery.

Brochet E, Czitrom D, Karila-Cohen D, Seknadji P, Faraggi M, Benamer H, Aubry P, Steg PG, Assayag P.

Department of Cardiology, Hopital Bichat, Paris, France. eric.brochet@bch.ap-hop-paris.fr

OBJECTIVES: The purpose of this study was to assess early temporal changes in myocardial perfusion pattern by myocardial contrast echocardiography (MCE) and their relation to myocardial viability in patients with reperfused acute myocardial infarction (AMI). BACKGROUND: Myocardial contrast echocardiography no-reflow is associated with poor contractile recovery after AMI. However, little is known regarding early reversibility of microvascular dysfunction and its relation to myocardial viability. METHODS: Intracoronary MCE was performed immediately after reflow and 9 days later in 28 patients with a first AMI and successful coronary recanalization (Thrombolysis in Myocardial Infarction trial grade 3 flow). Semiquantitative contrast score and wall motion score (WMS) were assessed in each initially asynergic segment at initial and repeat MCE study. Low dose dobutamine echocardiography (DE) was performed at day 10, and follow-up (FU) rest echocardiography was performed 6 weeks later. RESULTS: Among 200 initially asynergic segments, 49% exhibited no or heterogeneous contrast enhancement at initial MCE versus 24% at restudy (p < 0.001). Three groups of segments were defined according to early changes in contrast pattern: group A, "sustained no-reflow" (n = 17); group B, improved contrast score (n = 68), and group C, "sustained reflow" (n = 112). Group A segments showed no improvement in WMS at FU. In contrast, group B segments showed significant improvement in WMS at FU (p < 0.0001), and exhibited more frequently contractile reserve at DE (36% vs. 6%, p = 0.02) and contractile recovery at FU (34% vs. 7%, p = 0.03) than group A segments. Group C segments exhibited contractile reserve and contractile recovery in 47% and 51% of segments respectively. CONCLUSIONS: Improvement in MCE perfusion pattern may occur after initial no-reflow in the days following reperfused AMI and is associated with preservation of contractile reserve and gradual regional functional recovery.

PMID: 9857886 [PubMed - indexed for MEDLINE]

9: J Am Coll Cardiol 1998 Oct;32(4):890-7

Related Articles, Books, LinkOut

Prediction of short- and intermediate-term prognoses of patients with acute myocardial infarction using myocardial contrast echocardiography one day after recanalization.

Sakuma T, Hayashi Y, Sumii K, Imazu M, Yamakido M.

Division of Cardiology, Akane Foundation Tsuchiya General Hospital, Hiroshima, Japan. sakuma@urban.ne.jp

OBJECTIVES: This study sought to determine whether microvascular integrity in the risk area (RA) for myocardial infarction (MI) one day after recanalization predicts the outcome in patients with first acute MI. BACKGROUND: Immediately after recanalization, microcirculation in the RA is modified by both hyperemic response and microvascular impairment. METHODS: Fifty consecutive patients who underwent serial myocardial contrast echocardiography before and one day after recanalization (day 2) were studied. All patients had a completely occluded lesion in the left anterior descending coronary artery alone, and underwent successful reperfusion therapy. The relative size of the initial RA (RA ratio) and peak gray scale ratio (PGSR) within the RA on day 2 were determined. Patients were followed for a median of 22 months to evaluate clinical outcome. RESULTS: On day 2, PGSR was a median of 0.46. Study patients were subdivided into two groups, group A of 24 patients with acceptable opacification (PGSR > 0.46 on day 2) and group B of 26 patients without it. Major cardiac events (cardiac death, nonfatal MI and repeat admission for congestive heart failure) were more frequently observed in group B (28% vs. 4%, Cox hazard ratio=8.5, p=0.05, 95% confidence interval [CI] 1.03 to 69.9). The median value of the RA ratio was 0.45. Patients (n=15) with RA ratio > 0.45 on day 1 and PGSR on day 2 < or = 0.46 exhibited a 10.7-fold relative risk for major cardiac events (p=0.005, 95% CI 2.06 to 55.8) and a 3.69-fold relative risk for composite cardiac events (major cardiac events and target lesion revascularizations) after the initial intervention (p=0.004, 95% CI 1.51 to 9.04). CONCLUSIONS: The assessment of both the size of the initial RA and microvascular integrity on day 2 enables precise determination of the efficacy of reperfusion therapy and prediction of the short- and intermediate-term prognoses of patients with recanalized MI.

PMID: 9768708 [PubMed - indexed for MEDLINE]

Clinical implications of the 'no reflow' phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction.

Ito H, Maruyama A, Iwakura K, Takiuchi S, Masuyama T, Hori M, Higashino Y, Fujii K, Minamino T.

Division of Cardiology, Sakurabashi Watanabe Hospital, Osaka, Japan.

BACKGROUND: Recent studies demonstrated that the "no reflow" phenomenon after coronary reflow implies the presence of advanced myocardial damage. In this study, we verified the prognostic value of the detection of this phenomenon by studying complications, left ventricular morphology, and in-hospital survival after acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 126 patients with a first anterior AMI. All patients received coronary reflow within 24 hours of onset of symptoms and underwent myocardial contrast echocardiography (MCE) before and shortly after coronary reflow with an intracoronary injection of sonicated microbubbles. From contrast reperfusion patterns, patients were divided into two subsets: those with MCE no reflow (47 patients, 37%) and those with MCE reflow (79 patients). There was no difference in the frequency of arrhythmia or coronary events between the two subsets. Pericardial effusion and early congestive heart failure were observed more frequently in patients with MCE no reflow than in those with MCE reflow (26% versus 4%, P < .05; 45% versus 15%, P < .05, respectively). Congestive heart failure tended to be prolonged in those with MCE no reflow, and 3 patients (7%) of this subset died of pump failure. Left ventricular end-diastolic volume progressively increased in the convalescent stage in patients with MCE no reflow (early versus late, 145 +/- 43 versus 169 +/- 60 mL, P < .001), whereas it decreased in those with MCE reflow (154 +/- 42 versus 144 +/- 44 mL, P < .01). CONCLUSIONS: The substantial size of the MCE no reflow phenomenon at coronary reflow conveys useful information about an outcome of coronary intervention and left ventricular remodeling in individual patients with anterior wall AMI, although these are suggestive results in a limited number of patients.

PMID: 8548892 [PubMed - indexed for MEDLINE]