CABG in patients with left ventricular dysfunction: indications, techniques and outcomes
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Ischemic chronic heart failure (CHF) represents one of the cardiovascular diseases with the worst degree of morbidity and mortality in the western world, and with the highest health care costs. Despite several studies demonstrated that surgical revascularization (CABG), especially in the presence of viable myocardium, improve heart function, and therefore, survival, the matter remains unclear and controversial. In the late 1970s, the Coronary Artery Surgery Study showed that a subgroup of patients with coronary artery disease, angina, and reduce LV function had a significant survival benefit after CABG compared to those treated medically. The key concept behind this observation was the presence of viable myocardium, which can resume function following revascularization. In contrary, the surgical treatment for ischemic heart failure (STICH) trial, which randomized patients with CAD and LV dysfunction to evidence-based medical therapy or CABG plus medical therapy, failed to demonstrate at a median follow-up of 56 months a significant difference between the CABG group and the medical therapy group in the rate of death from any cause. However, the results of the STICH extension study (STICHES) at 10 years follow-up demonstrated that CABG is associated with a significant reduction in all-cause mortality, cardiovascular mortality, and readmission for heart compared to optimal medical therapy (OMT) in patients with severe ischemic LV dysfunction. Therefore, this review discusses the available evidences in literature, from observational studies to randomized trials, including operative techniques and controversial issues, in order to better clarify the role of CABG in the current management of ischemic patients with LVD.
KeywordsCABG Heart failure Left ventricular dysfunction
CHF represents one of the cardiovascular diseases with the worst degree of morbidity and mortality in the western world, and with the highest health care costs . Despite several retrospective studies demonstrated that surgical revascularization (CABG), especially in the presence of viable myocardium, improve heart function, and therefore, survival, the matter remains unclear and controversial. Indeed, these studies were conducted more than 40 years ago, before the availability of current guideline-based medical therapy for coronary artery disease and heart failure, and they did not include patients with severe left ventricular dysfunction. In contrary, the STICH trial , which randomized patients with CAD and LV dysfunction to evidence-based medical therapy or CABG plus medical therapy, failed to demonstrate at a median follow-up of 56 months a significant difference between the CABG group and the medical therapy group in the rate of death from any cause. However, the results of the STICH extension study (STICHES) at 10 years follow-up demonstrated that CABG is associated with a significant reduction in all-cause mortality, cardiovascular mortality, and readmission for heart failure compared to OMT in patients with severe ischemic LV dysfunction (LVD).
Therefore, this review discusses the available evidences in literature, from observational studies to randomized trials, including operative techniques and controversial issues, in order to better clarify the role of CABG in the current management of ischemic patients with LVD.
Prevalence of low ejection fraction in patients undergoing coronary artery bypass grafting
The reported prevalence of severe ischemic LVD in patients undergoing CABG in large series and registries has ranged from 3.4 to 15% . The differences may be partly explained by different definitions of severely depressed left ventricular function, even if most studies choose an EF of less than or equal to 35%. In a recent analysis of the society of thoracic surgeons national adult cardiac surgery database (STS NCD) among 439.092 isolated CABG procedures performed on adult patients between 2011 and 2014, the prevalence of LVD (EF < 35%) was 12.5%, with 3.6% of patients presenting with very poor EF less than 20% . In the Society for Cardiothoracic Surgery in Great Britain and Ireland National Database, among 23,740 cardiac procedures performed between 2010 and 2011, incidence of EF less than 30% was 6%, with 0.5% of patients presenting with severe LV dysfunction (EF < 20%). In our department, among 8555 patients operated of isolated CABG between 2000 and 2016, nearly 10% presented with EF less than 35%, and this incidence resulted slightly increasing in the last years. As a result of the steady increase in the incidence of congestive heart failure in developed countries, it is expected that a growing number of patients with ischemic cardiomyopathy and LVD will require myocardial revascularization.
Early and long-term outcomes
Patients with reduced EF (< 30%) undergoing CABG have been consistently shown in the literature to have higher operative mortality and reduced long-term survival compared with patients with preserved EF. However, 30-day mortality has significantly improved over time, passing from a 20% in the late 1980s to a 5% in patients operated on after 2000. This enhancement in operative outcome is certainly multifactorial and probably related to improvements in myocardial protection strategies and perioperative management of related comorbidity. Kunadian , in a meta-analysis including 4119 patients from 26 observational studies with ischemic LVD (mean preoperative EF = 24%) undergoing CABG, reported a mean estimated 30-day mortality of 5.4%, with a limited postoperative use of IABP (8%) and inotropic support (43%); a significant improvement in postoperative systolic function, as mean EF improved from 24 to 35%; a mean estimated 5-year survival rate of 75%. These results demonstrated that CABG can be performed in this subgroup of patients with acceptable operative mortality and long-term survival. The comparison between medical therapy and CABG in the treatment of chronic stable angina has been addressed in several early trials. Unfortunately, these results can hardly be applied to the contemporary management of patients with ischemic cardiomyopathy, because patients with severe LVD were largely excluded, and both surgical techniques and medical therapy have significantly improved. Besides, more contemporary trials evaluating treatments for ischemic heart disease that included an intensive medical regimen, such as the medicine, angioplasty, or surgery study (MASS-II) trial and the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, excluded patients with severe LV dysfunction. Even in modern trials comparing CABG and PCI, such as the synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) and the future revascularization evaluation in patients with diabetes mellitus: optimal management of multivessel disease (FREEDOM) trials, patients with severe LVD represent only nearly 2% of the enrolled patients. Then, until the STICH trial, data supporting the role of surgical revascularization for patients with LVD were primarily observational and often drawn from only a single institution. These studies comparing survival in patients treated surgically versus medically suggested uniformly that CABG enhances survival in patients with ischemic LVD. Reductions in mortality with surgery compared with medical therapy ranged from 10 to > 50%. However, most of these studies either date from the 1960s and 1970s, before the advent of beta-blockers and inhibitors of the renin-angiotensin-aldosterone system, or fail to provide sufficient detail to determine if medical management would be optimal by current standards.
The STICH trial and the STICHES study
The STICH trial  is the only prospective, randomized, controlled trial to specifically investigate the role of CABG in patients with LVEF < 35% who are also receiving OMT. In the analysis of data from the surgical revascularization hypothesis (enrolling 1212 patients), at a median follow-up period of 56 months, no significant difference was observed in the primary outcome of all-cause mortality between patients randomized to CABG versus OMT. However, the CABG group had improved rates of death from cardiovascular causes and improved rates of a combined endpoint of death from any cause and hospitalization for heart failure, as well as a greater improvement in measures of symptoms and quality of life. Moreover, the assessment of preoperative viability or inducible myocardial ischemia did not identify patients who would preferentially benefit from CABG. On the contrary, compared with functional imaging, assessment of the anatomical extent of the disease resulted a better predictor of benefit from CABG in patients with LVD. Indeed, patients with more advanced forms of ischemic cardiomyopathy (as expressed by the presence of three-vessel disease and more severe LV systolic dysfunction and remodeling) received the greatest benefit from surgical revascularization . This resulted in an overall statistically significant benefit of CABG over the entire follow-up period despite the higher early mortality with surgery compared with OMT. Interestingly, the results of the STICH extension study (STICHES)  demonstrated that at 10 years follow-up, all-cause mortality, cardiovascular mortality, and a composite endpoint of mortality and HF readmission were significantly reduced in CABG patients compared to OMT, and these results were more evident in younger compared to older patients .
Off-pump versus on-pump CABG
The off-pump technique (OPCABG) has been advocated by some authors in patients with LVD undergoing myocardial revascularization in order to minimize ischemic time and perioperative myocardial damage. In a meta-analysis including 1512 patients with LVD undergoing either OPCABG (498 patients) or on-pump CABG (1014 patients), Kunadian and colleagues  found that OPCABG had a non-significant hazard ratio of 0.71 for mortality when compared with the on-pump technique (in-hospital mortality was 5.4% vs. 4.4% for on-pump and off-pump respectively). This result needs to be interpreted with caution, given the small proportion of patients in this subgroup analysis that underwent OPCAB, and the fact that the studies included in this meta-analysis were not randomized. Furthermore, patients undergoing OPCAB usually have different baseline characteristics compared with patients undergoing on-pump CABG. This might in turn have a confounding effect on surgical mortality rates, independently by the surgical technique. Indeed, whether off-pump surgery might be beneficial among patients with severe LV dysfunction requires further evaluation.
Use of arterial graft
The use of bilateral internal thoracic arteries (BITAs) has been associated with improved outcomes following myocardial revascularization, especially in patients with a predicted survival greater than 10 years. However, the impact of a strategy of BITA grafting on survival is less clear for high-risk subgroups, such as those with low EF. In the milestone paper from Lytle’s group , low-EF patients undergoing BITA had an improved late survival compared with matched SITA patients with low EF, although overall survival among low-EF patients was significantly worse than those with normal LV function irrespective of the grafting strategy. A recent study by Galbut  showed a survival advantage associated with BITA grafting in a group of low-EF patients propensity-matched to SITA patients at 10 year post-CABG. However, any survival benefit disappeared in those patients with EF < 0.30. Recently, Mohammadi  in a cohort of 222 propensity-matched patients with LVD, demonstrated no long-term survival advantage of the BITA over the single ITA strategy. Taken together, these evidences seem to suggest that the use of a second ITA is not associated with improved survival following CABG among patients with LVD. One possible explanation for these results is that LV systolic dysfunction constitutes a powerful predictor of late mortality among CABG patients that may negate any potential advantage of BITA grafting.
Despite the enormous amount of data regarding myocardial protection reported in literature, very few studies (and no randomized clinical trial) addressed the role of cardioplegia type (crystalloid versus blood; cold versus warm; antegrade versus retrograde) in patients with LVD undergoing myocardial revascularization. The CABG Patch Trial  represented a high-risk group of 900 patients with ejection fractions < 36% who underwent CABG, with half randomly assigned to ICD implantation. Although not designed to address this issue, the trial collected limited data on cardioplegic type and perioperative events in addition to survival. The study demonstrated that (a) crystalloid cardioplegia was associated with an increased risk of postoperative myocardial damage, inotrope, and IABP use and incidence of conduction disturbances compared to blood cardioplegia. (b) Warm cardioplegia was associated with superior right ventricular protection, lower IABP use and less conduction defects compared to cold cardioplegia. (c) Combined antegrade/retrograde cardioplegia was associated with less postoperative myocardial damage (inotrope/IABP use and conduction defects) compared to antegrade cardioplegia alone. Despite these findings, no significant differences in 30-day or late survival, as well as in postoperative low-output syndrome or acute MI was observed between the different type of myocardial protection strategy.
Preoperative IABP use
The perioperative use of intra-aortic balloon pump in cardiac surgery is widespread and supported by a large amount of data. Recently, the role of IABP in the setting of high-risk patients undergoing myocardial revascularization has been challenged by the IABP-SHOCK-II Trial  that showed no difference in short- and long-term survival in patients randomized to intra-aortic balloon pump versus standard treatment in acute coronary syndrome complicated by cardiogenic shock and planned for revascularization. However, in a recent meta-analysis of 8 randomized clinical trials, including 625 high-risk elective coronary artery bypass graft patients, Zangrillo and colleagues  reported that preoperative IABP insertion was associated with a significant reduction in the risk of perioperative mortality (3.5% vs. 11% in IABP versus non-IABP groups). The benefit on mortality reduction was confirmed restricting the analysis to trials with low risk of bias, to those reporting a 30-day follow-up and to patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass.
Myocardial viability assessment
Viability of myocardial tissue is the central principal, which underpins reperfusion therapies. In the context of ischemic chronic LVD, identifying myocardial hibernation is of clinical relevance, as it represents potentially salvageable myocardial tissue. Myocardial viability can be assessed by several methods, such as dobutamine stress echocardiography (eventually associated with strain analysis), single-photon emission CT, positron emission tomography, and cardiovascular magnetic resonance. Each of these methods presents pros and cons, with different sensitivity and specificity. Should “viable” myocardial tissue be present, restoration of adequate coronary blood flow should in theory improve myocardial performance and LVEF, with the hope of translating into improved long-term outcomes. On these premises, numerous nonrandomized retrospective studies in the early 1990s evaluated the value of viability testing in the decision-making process concerning myocardial revascularization in patients with ischemic LVD. A meta-analysis of these trials revealed a significant association between revascularization and improvement in mortality utilizing viability testing in patients with known ischemic cardiomyopathy, irrespective of imaging modality chosen . These initial studies, although favorable, shared several limitations (small studies, wide temporal distribution, retrospective analysis, different methods of viability assessment, incomplete adherence to optimal medical therapy) and lacked sufficient power and sample size to provide conclusive statement on viability assessment in this subgroup of patients. In the recent years, the impact of preoperative myocardial viability assessment on the outcomes of surgical revascularization in patients with ischemic LVD was investigated in some important multicenter randomized trials. The PET and recovery following revascularization-2 (PARR-2)  Trial and the Ottawa-FIVE substudy of the PARR-2 Trial  demonstrated a statistically significant reduction in the primary composite endpoint within the FDG PET-guided revascularization group in comparison with the standard therapy arm, suggesting that preoperative myocardial viability assessment could have a prognostic benefit in centers with proved experience in cardiac imaging. In the heart failure revascularization trial (HEART) , patients with ischemic LVD and preoperative assessment of myocardial viability with dobutamine echocardiography were randomized to CABG or medical therapy and followed up over a 5-year period. The primary outcome revealed non-inferiority of medical therapy. This study was, however, prematurely interrupted due to slow recruitment, and thus resulted underpowered due to small sample size. In the revascularization hypothesis of the STICH trial, half of the enrolled patients underwent assessment of myocardial viability by means of either single-photon emission-computed tomography or low-dose dobutamine echocardiography. Despite patients with viable tissue experienced a significantly lower 5-year mortality compared to patients without myocardial viability (37% vs. 51%), the viability analysis did not identify patients who would preferentially benefit from CABG over OMT . Moreover, there was no significant interaction with respect to mortality between viability status and assignment to CABG or OMT. Despite some limitations (including the lack of more advanced modality of viability assessment like PET and cardiac MRI), this study represents the largest analysis of the influence of myocardial viability on clinical endpoints in patients with ischemic cardiomyopathy to date, and was the first to assess the differential effect of viability on revascularization versus medical management.
Surgical Ventricular Reconstruction (SVR) associated to myocardial revascularization in patients with LV dysfunction
The concept behind the ventricular reconstruction is based on the exclusion of the scar tissue, thereby reducing the ventricle to a more physiological volume, reshaping the distorted chamber, and improving cardiac function through a reduction of LV wall stress in accordance with the principle of Laplace’s law. Since LV wall stress is directly proportional to LV internal radius and pressure and inversely proportional to wall thickness, any intervention to optimize this relationship would be beneficial in terms of either improving wall compliance and reducing filling pressure or by increasing the extent and velocity of systolic fiber shortening . Furthermore, myocardial revascularization usually combined with the reconstruction of failing ventricles aims to treat the underlying coronary artery disease. Finally, in case of concomitant functional chronic ischemic MR, SVR offers either the possibility to repair the mitral valve through the LV opening or the potential of improving mitral functioning by reducing LV volumes and papillary muscles distance .
SVR surgical technique
The choice to perform SVR should be based on a careful evaluation of patients, including (1) HF symptoms, which should be predominant over angina; (2) accurate measurements of LV geometric and hemodynamic parameters; (3) careful evaluation of mitral valve; (4) precise assessment of the transmural extent of myocardial scar tissue, and viability of regions remote from the scar, and should be performed only in centers with a high level of surgical expertise .
Previous anterior or posterior MI, as evaluated by electrocardiogram or CMR, which should be preferred, when available and not contraindicated.
LV end-systolic volume indexed > 60 mL/m2. Preoperative LVESV should be carefully evaluated to avoid the selection of patients with small ventricles for which the likelihood for diastolic function worsening is high .
LV dysfunction with regional asynergy, either dyskinetic or akinetic; when LV asynergy is severe and diffuse, SVR should be performed only if regions remote from the scar show some degree of detectable contraction.
In predominant HF symptoms [New York heart association (NYHA) class III/IV], the indication can also be expanded to patients presenting with ventricular arrhythmias and/or angina who need surgical revascularization if the previous conditions are present, to avoid further remodeling.
Severe right ventricular dysfunction (biventricular-dilated cardiomyopathy), in our experience, right ventricular dysfunction, as reflected by an impaired TAPSE, correlates with LV dysfunction, and it is an important predictor of long-term outcome in HF patients undergoing SVR ;
Restrictive diastolic pattern associated with high functional class and MR showed that diastolic dysfunction (E/A ratio > 2) increases the operative risk of mortality when associated with mitral regurgitation and a New York Heart Association class greater than II.
San Donato experience
Indications and closing remarks
The decision of whether to proceed with surgical revascularization in a patient with ischemic cardiomyopathy is an increasingly common one, given the rising prevalence of this condition. Unfortunately, it is also a difficult one because of the complexity and variability of the clinical presentations and, until recently, because of the paucity of data from randomized clinical trials. In summary, the results of the available literature (including the STICHES data) seem to support a significant benefit of CABG plus OMT over medical therapy alone across all clinically relevant long-term outcomes in patients with LVD. Although more extensive CAD and worse LV dysfunction and remodeling may be intuitively thought to be associated with increased operative mortality, those characteristics are found among patients who derive the greatest benefit from revascularization and, hence, are those in whom CABG may not be delayed. The role of preoperative assessment of myocardial viability on determining the treatment’s choice remains partially unsolved. On the basis of the STICH results, however, assessment of myocardial viability should not be the arbitrating factor for therapy choice. These considerations are reflected in current recommendations for revascularization in the 2013 American College of Cardiology/American Heart Association guideline for the management of heart failure . The guidelines indicate that, in the absence of angina, CABG may be considered for improving survival in patients with ischemic heart disease with LVD, whether or not viable myocardium is present (Class IIb, Level of Evidence: B). Finally, the choice to add SVR to CABG should be based on a careful selection of patients, coming from a tight collaboration between surgeons, cardiologists, and radiologists. Despite controversies which probably continue for a long time, SVR seems to have still a role in treatment of ischemic HF patients, especially if a postoperative LVESV index < 70 mL/m2 can be predictably achieved.
Compliance with ethical standards
The manuscript is original and has not been published previously (partly or in full). No data have been fabricated or manipulated. Consent to submit has been received explicitly from all co-authors. Authors whose names appear on the submission have contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results.
Conflict of interest
The authors declare that they have no conflict of interest.
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