Patterns of Left Ventricular Dilatation With an Opened Artery After Acute Myocardial Infarction
Missing Links to Long-Term Prognosis
Ventricular remodeling, the geometric adaptation to injury after acute myocardial infarction, affects the function of both non-infarcted and infarcted muscle, as well as prognosis. Ventricular dilatation bodes especially poorly for late survival.1 It has long been recognized that early infarct expansion is the result of lengthening of the noncontractile region undergoing a stress response with secondary volume overload hypertrophy, a process which maybe progressive over time.2–4⇓⇓ The extent of the initial myocardial damage is linked both to the magnitude and, to a lesser degree, the timing of left ventricular (LV) dilatation and ultimately survival.5 Moreover, ventricular remodeling (enlargement) is influenced not only by infarct size but also the type of infarct healing and coexistent LV wall stresses.5
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The most effective interventions to limit or prevent ventricular dilatation after infarction are those addressing the initial myocardial insult through the earliest and most sustained reperfusion therapies.6 The re-establishment of coronary blood flow to the infarcted region, even if delayed in some circumstances, is thought to attenuate ventricular remodeling. Modification of those biochemical and physiological factors that deform the compromised ventricle also influences late ventricular adaptive responses and prognosis. It is now common knowledge that instituting afterload reduction improves ventricular remodeling, attenuates infarct expansion, and provides long-term clinical improvement.1
However, of the three major factors involved in the acute infarct remodeling sequence, cardiologists can exert the most influence only at the onset through the timeliness and completeness of reperfusion with successful thrombolysis and/or angioplasty with stenting. Because of the many uncontrollable variables of myocyte salvage, considerable controversies remain regarding the links between the effectiveness of an opened artery after infarction on long-term ventricular function and consequent survival statistics.7
Further insight into the sequence and significance of LV responses is provided by Bolognese et al.8 In their examination of 284 consecutive patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction, Bolognese et al8 obtained serial echocardiographic and angiographic studies at 24 hours, 1 month, and 6 months. Late followup (61±14 months) was available in all but 4 patients. Despite excellent infarct-related artery patency rates at 6 months, 30% of patients showed LV dilatation with >20% increase in end-diastole volume at 6 months compared with 24 hours. Cardiac cath and combined adverse cardiac event rates were significantly higher in patients with as compared with those without LV dilatation. End-systolic volume at 6 months and age were strong predictors of late cardiac death. Three patterns of dilatation, early, late, and progressive, were identified. Early dilatation occurred between 24 hours and 1 month, late dilatation occurred from 1 month to 6 months, and progressive dilatation was defined as a continuum of enlargement from day 1 through 1 and 6 months. These 3 patterns were detected in 15%, 14%, and 13% of the ventricular dilation group, respectively. However, there was no difference in survival statistics among the 3 patterns of LV dilatation. Thus, LV dilatation in general, but not a specific pattern of dilatation, was associated with a poor long-term outcome.
An opened artery hypothesis was also challenged in this study.8 Similar low restenosis and reocclusion rates during the 6-month follow-up period were present in patients with and without LV remodeling (restenosis rates were 23% versus 24% and reocclusion was 5% versus 6%, respectively, both P=NS). Restenosis rates among the 3 patterns of LV dilatation were similar (15%, 27%, and 31%, all P=NS), as were the reocclusion rates (2%, 5%, and 6%, respectively). Thus, at 6 months, there was an unfortunate 30% of patients with patent infarct related arteries who went on to have LV dilation. An open artery also did not link with a specific pattern of dilation.
The investigation of Bolognese et al8 closes some of the links between LV remodeling and patency of the infarct-related artery, in that remodeling, more than late artery patency, influences prognosis even among successfully reperfused patients. This article8 highlights a novel observation, namely that LV remodeling after acute myocardial infarction occurs in a heterogeneous fashion with no specific pattern of LV dilatation differentiating patient survival.
The investigators should be complemented for the detailed long-term study of this relatively low-risk population, treated with optimal reperfusion therapy and having serial coronary angiography at 1 month and again 6 months later. The quantitation of LV function and size with serial echocardiography is also a key observation linking these phenomena. The study findings are consistent with our current understanding of infarct physiology, myocardial functional recovery, and remodeling. Infarct size,4 anterior infarct location,9 perfusion status of the infarct-related artery,6 heart failure on admission,10 and a restricted pattern of LV filling11 have all been identified as major predictors of LV dilatation after infarction. These observations demonstrate that after acute myocardial infarction, even with patent infarct-related arteries and a relatively small initial end-systolic volume, many patients remain at risk for ventricular remodeling despite an early favorable examination. Bolognese et al8 emphasize that acute myocardial infarction patients should be evaluated serially and all available therapies to reduce LV remodeling should be instituted early and maintained indefinitely.
These data also leave us with some questions, some missing links remaining to be answered. While the size of the infarction is crucial to LV remodeling, is the response and preservation of the microcirculation at the time of injury also related to the timing and mechanism of late remodeling? For example, Neumann et al12 demonstrated that glycoprotein receptor blockade with standard therapy during acute PCI for infarction was associated with improved LV function and coronary hyperemia over a 2 week follow-up. Although angiography was serially performed, this study8 did not examine TIMI flow or myocardial blush scores13 or note the incidence of slow or no re-flow during intervention14 to link microvascular responses to LV recovery.
Why is the infarct size not related to the pattern of LV remodeling? Although the magnitude of creatine kinase enzyme elevation was correlated with LV dilatation, these data were not differentiated among the 3 patterns of dilatation. What mechanisms are responsible for producing these types of dilatation over the follow-up period?
What are the related factors and the meaning of the 3 different patterns of LV dilatation? Although the pattern of dilatation did not provide any additional prognostic information, perhaps the mechanisms associated with these patterns might yield important new relationships regarding methods of myocardial preservation. Beyond establishing a patent infarct-related artery, stabilizing microvascular integrity, and reducing the time to reperfusion, are there adjunctive methods of myocardial preservation, such as intravenous or intracoronary adenosine,14,15⇓ that can be used to further limit LV remodeling?
Bolognese et al8 re-emphasize that the LV remodeling process is directly linked to the infarct size and the extent of wall motion abnormality during the acute phase of infarction. Over time, remodeling produces a hemodynamic improvement of a compensatory nature (lowering LV filling pressure and increasing cardiac output), which seems to occur at the expense of significant increase in left ventricular chamber volumes and ultimately survival.9 Improving methods of myocardial preservation and protection during acute infarction with less late remodeling will close missing links for patient survival after acute infarction.
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
- ↵Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation. 1990; 81: 1161–1172.
- ↵Weisman HF, Bush DE, Mannisi JA, et al. Cellular mechanisms of myocardial infarct expansion. Circulation. 1988; 78: 186–201.
- ↵Gaudron P, Eilles C, Kugler I, et al. Progressive left ventricular dysfunction and remodeling after myocardial infarction: potential mechanisms and early predictors. Circulation. 1993; 87: 755–763.
- ↵Pfeffer MA, Pfeffer JM, Steinberg C, et al. Survival after an experimental myocardial infarction: beneficial effects of long term therapy with captropril. Circulation. 1985; 72: 406–412.
- ↵Bolognese L, Neskovic A, Parodi G, et al. Left ventricular remodeling following primary coronary angioplasty: patterns of left ventricular dilation and long term prognostic implications. Circulation. 2002; 106: 2351–2357.
- ↵McKay RG, Pfeffer MA, Pasternak RC, et al. Left ventricular remodeling following myocardial infarction: a corollary to infarct expansion. Circulation. 1986; 74: 693–702.
- ↵Neumann F, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockage on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation. 1998; 98: 2695–2701.
- ↵Gibson CM, Cannon C, Murphy S, et al. Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation. 2002; 105: 1909–1913.
- ↵Mahaffey KW, Puma JA, Barbagelata A, et al. Does adenosine in conjunction with thrombolysis reduce infarct size? Results from the controlled, randomized AMISTAD Trial. Circulation. 1997; 96 (suppl I): I-206–I-207.
- ↵Marzilli M, Orsini E, Marraccini P, et al. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000; 101: 2154–2159.