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Preserving Left Ventricular Function during Percutaneous
Coronary Intervention
Perhaps we interventionists should be more aware than we currently are of our patients’ left ventricular (LV) function or what angioplasty might do to that LV function. I am not suggesting that we don’t attach importance to this vital detail. But let’s face it, most of us don't consciously plan to preserve myocardium at all costs when we are confronted with a difficult bifurcation lesion. To the battle-ravaged ventricle that has endured the torment of hypertension, diabetes, a few previous non-ST-elevation myocardial infarctions (NSTEMIs), along with the regular pulses of alcohol thrown in, losing even a not-too-substantial side branch could well be the turning point on the mortality curve. Sometimes the situation demands that the sacrifice be made for “a greater good”, and that’s fair enough. However, let us remind ourselves that angioplasty, particularly elective percutaneous coronary intervention (PCI), is a cause of iatrogenic LV systolic dysfunction and may be more of a problem than we imagine or know (I am not aware of a randomized trial on this).
Relationship between myocardial necrosis and LV systolic function. Myocardial necrosis following myocardial infarction (MI) leads to LV dilatation followed by LV systolic dysfunction as a result of remodeling. Cardiac remodeling is generally accepted as a determinant of the clinical course of heart failure. Early infarct expansion occurs as the result of lengthening of the noncontractile region undergoing a stress response with secondary volume overload hypertrophy and is often progressive over time.1,2 About 26% of patients with acute myocardial infarction (AMI) develop limited dilatation and a further 20% progressive LV dilatation starting within hours-to-days after AMI, leading to significant LV systolic dysfunction at 1.5- and 3-year follow up.2 The process of ventricular enlargement can be influenced by three interdependent factors: infarct size, infarct healing and ventricular wall stresses.1 A useful way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in limiting ventricular enlargement. Drug therapy with angiotensinconverting enzyme (ACE) inhibitors, angiotensin receptor-blockers (ARB), beta-blockers and aldosterone antagonists have all been shown to limit or reverse remodeling if started early in the post-infarct stage.34
Evidence of the effect of PCI on LV function at mediumand long-term follow up. Effect on LV systolic function. Bolognese et al5 examined 284 consecutive patients undergoing primary percutaneous coronary intervention (PCI) for AMI by assessing LV function via echocardiographic and angiographic studies at 24 hours, 1 month and 6 months. Despite excellent infarct-related artery patency rates at 6 months, 30% of patients showed LV dilatation with a > 20% increase in end-diastole volume at 6 months compared with 24 hours. LV dilatation at 6 months was associated with severe long-term LV systolic dysfunction and a poor prognosis, irrespective of the type of LV remodeling — early, late or progressive. Another study using 3-dimensional transthoracic echocardiography found remodeling to occur in one-third of patients at 12 months following primary PCI for ST-elevation MI (STEMI).6
Successful rescue PCI within 3–24 hours of the onset of chest pain has been associated with improved LV systolic function at a mean follow-up period of 22 months.7 In this study, baseline and repeat ventriculograms were used to assess LV systolic function. Other studies of primary PCI have also reported improved LV systolic function compared to thrombolysis.8 Some other studies have suggested benefit in patients with hibernating myocardium.9
Interestingly, late PCI on persistent total occlusions 3–28 days after MI did not reduce rates of death, reinfarction or heart failure (or LV ejection fraction) compared with optimal medical therapy in the large OAT10 and TOSCA 211 studies. There appears to be no role for routine delayed PCI in improving LVEF in stable patients with an occluded infarct-related artery after MI.
Effect on LV diastolic function. One of the causes of diastolic dysfunction is coronary artery disease.12 Acute coronary syndromes (ACS) may present with acute heart failure purely as a result of exacerbation of diastolic dysfunction (in the absence of any systolic dysfunction).13 PCI does improve diastolic function in such patients but patients with hypertension (the most common subset of patients with diastolic dysfunction) and AMI have a higher propensity to develop heart failure postprimary PCI than those without hypertension.14 Henein and colleagues15 reported improvement in both systolic and diastolic function after successful angioplasty in a small study, attributing the baseline LV dysfunction to the coronary lesions. Diastolic dysfunction in coronary disease becomes more pronounced with aging and produces significant morbidity, especially if atrial fibrillation or systolic dysfunction is superimposed.13
Difficulties faced by interventionists. Let us look at the common scenarios during intervention. A lot of the elective PCI patients will have undergone LV angiography, and in those with preserved LV systolic function, losing a small side branch might not matter too much (although the numbers might add up in multivessel PCI if we are not careful). A number of PCI centers have adopted the “coronary angiography? proceed to PCI if needed” approach though, and perhaps in that setting of rapid, in-the-lab decision-making under time pressure, the importance of the recorded LV function fades slightly and takes second priority in the wider scheme of things, particularly with respect to the ensuing PCI procedure. It might be that if we had all signed up to the “no compromise on LV function if possible” approach beforehand, and had more time to review the pictures and consider a plan in relaxed circumstances, we would have noticed the mild LV systolic impairment and referred the patient for coronary artery bypass grafting (CABG) instead, given the complexity of the PCI procedure, despite complete confidence that a reasonable angiographic final result would be achieved, but also mindful that significant compromise of LV function cannot be guaranteed.
Adopt a policy of limiting LV necrosis during PCI? I work at a center where we treat outpatient transfers from surrounding smaller hospitals. I am in contact with the transferred patient for a few hours only, between their entry to our cardiology outpatient unit, to their departure back to the referring hospital if the PCI goes well. Often, details of the clinical background are sketchy apart from the information related to the ACS. Given that we all have started treating patients > 85 years of age with PCI, and their risk of heart failure is often high because of their high cardiovascular risk (e.g., a diabetic smoker with hypertension and hyperlipidemia), I often wonder if it would be best to adopt a policy of PCI in these and other patients only if the procedure presents a small risk of compromising LV function. Medical treatment might often be a better option than “gung-ho” PCI. Incomplete knowledge of the background comorbidities in such circumstances makes me uncomfortable when deciding whether to proceed with PCI in such patients.
PCI in poor LV systolic function. In those with already compromised LV systolic function, our PCI approach should include consideration of intra-aortic balloon pump (IABP) support. This is, without a doubt, the appropriate strategy for post-MI cardiogenic shock patients, as evidenced by the results of the SHOCK trial.16,17 In those without shock but with LVEF ≤ 30%, elective IABP might also be a wise choice before starting the PCI procedure to minimize the 20% risk of vascular instability in this group of patients and to ensure an uncomplicated and successful outcome.18 This strategy has been ratified in the ACC/AHA guidelines on PCI.19 The mechanism of benefit appears to be that IABP counterpulsation helps to maintain cardiac output by reduction of the afterload (with consequent reduction of oxygen consumption and myocardial ischemia) and may augment coronary perfusion.20,21
Distal protection and thrombectomy. Should we consider distal embolic protection to limit damage to LV function? Although distal embolic protection was not seen to be beneficial in patients undergoing primary PCI in the EMERALD (Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris) study,22 there is good evidence for their benefit in PCI of saphenous vein grafts23 and in those with angioscopically proven plaque rupture causing acute STEMI.24 The latter two would certainly be strong indications to use distal protection for the microvasculature. There is increasing evidence that thrombectomy prior to stent implantation in primary PCI might be helpful in improving myocardial perfusion by protecting the microvasculature, thereby limiting LV systolic dysfunction.25,26
PCI procedure is an opportunity to assess LV function. Our other responsibility is to ensure that all patients undergoing a PCI procedure have their LV function assessed and documented. This does not refer merely to those hospitalized with an ACS, as required by the United Kingdom MINAP (Myocardial Infarction National Audit Project) database,27 but all patients undergoing PCI, since this is our big chance to pick up those with asymptomatic LV dysfunction and start treatment with an ACE-inhibitor to prevent progression to overt heart failure. This is also our opportunity to start treatment to prevent heart failure for patients with high cardiovascular risk (as those undergoing PCI would be) and normal LV function. There is good evidence that in patients with high cardiovascular risk (those with diabetes, hypertension, hyperlipidemia and previous cardiovascular disease), early intervention with ACE inhibitors, angiotensin receptor-blockers, statins or antiplatelet therapy with clopidogrel significantly reduces the occurrence of heart failure, even when LV systolic function is normal.28–32 To be fair, assessment of LV function does take place during left heart catheterization in most cases, but I have a reason to emphasize this point. I have often been guilty myself of omitting the LV angiogram during the cardiac catheterization merely to cut short the proceduretime (in my enthusiasm to proceed to launch into the PCI, particularly in ACS and primary PCI cases), with the instruction to perform an echocardiogram later on, which didn’t actually happen in that admission. That brings me to another point: the timing of LV function assessment following a MI.
Early assessment of LV function in ACS. There is a need to assess LV function early after ACS if the full therapeutic benefit of the new aldosterone antagonist eplerenone is to be obtained. The EPHESUS trial involved 642 patients who were randomized 3 to 14 days after AMI if they had signs and symptoms of heart failure and an LVEF ≤ 40% to eplerenone or placebo in addition to optimal medical treatment. A significant reduction in overall mortality, death from cardiovascular (CVS) causes or hospitalization from CVS causes was seen in the eplerenone group at a mean follow up of 16 months.33 Much of the benefits occurred early. At 30 days after randomization,34 eplerenone reduced the risk of allcause mortality by 31% (3.2% vs. 4.6% in eplerenone- and placebo-treated patients, respectively; p = 0.004), and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone- and placebo-treated patients, respectively; p = 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p = 0.003), and the risk of sudden cardiac death by 37% (p = 0.051). In order to commence eplerenone early after MI, all such patients must undergo an early assessment of LV function, preferably by echocardiography.
Reduce door-to-balloon time. There is enough evidence now to call for a 24-hour/7 days per week primary PCI program wherever possible in order to improve outcomes and reduce LV dysfunction in STEMI patients.8 The other important call is for the process of primary PCI to be facilitated with a view to reducing the time from symptom-onset to PCI.35 This means that we need to strive for better organization to reduce transfer times and minimize delays in primary PCI36 to ensure even less LV dysfunction and mortality. Based on current evidence, delayed PCI in untreated STEMI patients should be driven by symptoms rather than be a routine strategy.10,11
Rationale for preserving LV function during PCI at all costs. Why should we worry about causing a bit of LV dysfunction during PCIs which are often vital procedures to the patient? Because these things add up and add to what might be already there. And there is no denying that LV function is the major driver and predictor of outcomes in coronary artery disease,37–39 and also because of the heart failure epidemic that is threatening many of our patients. Let me refresh your memory with the statistics again. In the United Kingdom population, 3–20 per 1000 are currently suffering from heart failure.40 The number increases to more than 80 per 1000 people who are > 75 years of age. Year-on-year, the number of heart failure patients is on the rise, with at least 1 new case per 1000, and an annual increase in new patients of 10%.40 My aim is not to harp on the issue of side branch loss from PCI, but to focus the spotlight on what we could all do to prevent heart failure.
My proposal. I propose that for all primary PCIs, rescue PCIs, percutaneous intervention for NSTEMI, as well as elective complex PCIs (including those where an apparently simple PCI has become complicated by side branch loss, dissection, no-reflow, etc.), an echocardiogram should be performed to document LV function immediately prior to the procedure and again at 6 months following the procedure. Significant LV dilatation of > 20% in end-diastolic volume or a reduction of ejection fraction should indicate the need for vigorous treatment with heart failure drugs such as ACE inhibitors, angiotensin receptor-blockers, beta-blockers and, if required, spironolactone. LV end-diastolic pressure (LVEDP) should be recorded and LV angiography should also remain part of the diagnostic coronary angiographic study whenever possible, since these provide useful information on LV function. Troponin measurements post-PCI, in my view, do not add much to the assessment of remodeling following acute ischemic syndromes, and need not be routinely performed.
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