Ischemic cardiomyopathy (ICM), characterized by significant left ventricular dysfunction with an ejection fraction (LVEF) ≤40% due to coronary artery disease (CAD), accounts for more than 60% of congestive heart failure cases and is associated with high morbidity and mortality rates. Treatment for ICM aims to extend survival, improve quality of life, and reduce both cardiac and non-cardiac complications. Although ventricular dysfunction in these patients is not necessarily irreversible, coronary artery bypass grafting (CABG) may enhance ventricular function by restoring blood flow to ischemic segments, thereby improving clinical outcomes. In fact, revascularization has been shown to significantly increase LVEF in up to 60% of patients with hibernating myocardium, a topic previously discussed in the blog.

Despite its significance, ICM patients have been systematically excluded from most clinical trials, leading to uncertainty about the applicability of existing results to this population. The 2021 ACC/AHA guidelines recommend surgical revascularization for patients with ICM and an LVEF <35% to improve survival. However, no specific recommendations exist regarding the optimal revascularization strategy for these patients. On the other hand, the ESC/EACTS guidelines recommend surgical revascularization as the first line of treatment in this specific population when an acceptable surgical risk is present.

In this review article, based on the latest evidence, readers will find a comprehensive analysis of studies comparing optimal medical therapy (OMT), percutaneous coronary intervention (PCI), and CABG in the search for the best option for patients with ICM. Additionally, it explores various revascularization strategies in depth, focusing on the benefits and limitations of techniques such as on-pump CABG (ONCABG), off-pump CABG (OPCAB), and hybrid revascularization. Throughout the study, coronary graft options are examined, with particular emphasis on the use of arterial grafts such as the left internal thoracic artery (LITA), right internal thoracic artery (RITA), and radial artery (RA), as well as special considerations required to maximize outcomes in high-risk patients.

Understanding the methodology used in this study is important, as it follows the Arksey and O’Malley framework, designed to conduct a “scoping review.” This methodology is ideal when a broad overview on a specific topic is desired, in this case, myocardial revascularization in patients with ischemic left ventricular dysfunction. Unlike other types of reviews that may focus solely on high-quality studies or specific designs, this type of review seeks to include all relevant literature, regardless of study design. This approach allows for identifying both what is known and unknown about a topic, providing a broad map of available research. Following this methodology, the study was able to narrow an initial set of 358 references to 134 relevant studies, ensuring that the selection of studies was carried out with precision and consistency.

Evidence on Optimal Strategy in Patients with LVEF ≤35%

Clinical Guidelines: Although European guidelines recommend CABG as a Class I indication for patients with multivessel or left main coronary artery disease presenting with angina or heart failure and with an acceptable surgical risk, the optimal strategy for these patients with severe left ventricular dysfunction remains unclear. PCI is recommended as a Class IIa indication in patients with single or double-vessel disease and could also be considered for those with three-vessel disease with a low SYNTAX score, taking into account patient expectations for complete revascularization, diabetic status, and comorbidities. The AHA guidelines consider CABG for patients with moderate to severe left ventricular dysfunction (LVEF 35-50%) as Class IIa, and it may also be considered for those with severe left ventricular dysfunction (LVEF <35%) with significant left main coronary artery disease. PCI is preferred as an alternative to CABG in selected, stable patients with significant left main coronary artery disease, favorable anatomical conditions, or clinical characteristics predicting a significantly greater risk of adverse outcomes with surgery. Therefore, despite recommendations from European and AHA guidelines, the current understanding of myocardial revascularization in patients with severe left ventricular dysfunction (LVEF ≤35%) remains uncertain. While CABG is recommended as the first-line treatment in patients with multivessel or left main coronary artery disease, PCI is seen as a valid alternative in certain scenarios. However, the optimal revascularization strategy for these patients is still not clearly defined.

Most Relevant Studies:
The STICH trial, which evaluated the efficacy of CABG compared to OMT in patients with LVEF <35%, found no significant differences in overall mortality in the mid-term follow-up. However, in a later analysis with a median follow-up of 9.8 years (STICH Extended), a reduction in mortality was observed in the CABG group (16% reduction in all-cause mortality). Subgroup analyses indicated that patients with three-vessel disease (p = 0.04) or severely remodeled left ventricles (end-systolic left ventricular volume index >78 mL/m² or LVEF <27%; p = 0.03) appeared to gain the most benefit from revascularization. Despite these findings, the methodological limitations of the study, such as the substantial crossover rate of 17%, the lack of objective ischemia evaluation, and the inclusion of patients without considering myocardial viability (with a low proportion of patients showing viability), raise questions about the trial’s ability to accurately identify patients who would benefit most from revascularization.

The SYNTAX trial, with a five-year follow-up, showed that CABG provided a significant advantage for patients with complex lesions in three vessels or left main coronary artery disease. However, it is noteworthy that patients with ICM and an initial LVEF ≤30% constituted a minority within the CABG group, representing only 2.5% compared to a mere 1.3% in the PCI group, which could limit the generalizability of these findings to this specific population.

The HEART trial was designed to evaluate the feasibility of different revascularization strategies in patients with ICM and LVEF <35% with residual myocardial viability based on conventional imaging tests, such as dobutamine stress echocardiography, angiography, and positron emission tomography (PET). Although the initial plan was to include 800 patients, only 138 were randomized, and no significant differences were found between OMT and invasive revascularization in the five-year follow-up.

A recent meta-analysis comparing various revascularization strategies in patients with CAD and depressed LVEF demonstrated that CABG provides significant advantages over PCI and OMT, particularly in terms of survival and reductions in repeated revascularizations or reinfarctions. However, this benefit is more clearly observed in the long term. An important limitation to consider in most of these studies is that medical therapies did not include modern medications, such as angiotensin receptor-neprilysin inhibitors (ARNIs) or sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors), which have shown to improve cardiovascular outcomes.

Patients with left ventricular dysfunction pose significant challenges in coronary surgery due to their increased risk of complications and early mortality. However, these are precisely the patients who could benefit most from CABG.

Despite the evidence supporting CABG as the preferred revascularization strategy, most data come from observational studies, highlighting the need for more ad hoc randomized controlled trials (RCTs) to identify the most beneficial strategy and optimize treatment for these complex patients.

Surgical Revascularization Strategies and Indications

1. Off-Pump Coronary Artery Bypass (OPCABG) vs. On-Pump Coronary Artery Bypass (ONCABG):

OPCABG can provide significant advantages, particularly in high-risk patients, by reducing global myocardial ischemia and limiting the systemic inflammatory response, which may result in improved postoperative outcomes. Compared to ONCABG, OPCABG has shown benefits in some studies, including lower hospital mortality, reduced postoperative neurological events, and decreased need for prolonged ventilation. However, the debate is ongoing, and studies have shown mixed results when comparing both techniques:

The ROOBY trial indicated that although short-term outcomes did not significantly differ between ONCABG and OPCABG, long-term mortality was higher with OPCABG. However, this conclusion has been questioned due to limitations in the study’s design, such as the selection of surgeons and the limited representation of patients with left ventricular dysfunction. The ROOBY follow-up study, which assessed the long-term outcomes of these techniques, found no significant advantage of OPCABG in terms of outcomes or costs, concluding that both techniques are complementary and that neither should be preferred over the other in patients who are candidates for both. However, in patients with extremely low left ventricular function (LVEF 10-20%), OPCABG proved to be a viable option, with a reasonable mortality rate (11%) and a significant improvement in average LVEF to 35% at one-year follow-up.

Recent data, such as those from the STS registry, suggest that OPCABG may be a favorable option for patients with left ventricular dysfunction, particularly those with comorbidities and high preoperative risk. Despite performing fewer distal anastomoses, OPCABG does not appear to increase long-term mortality in older patients, highlighting its potential as a viable revascularization strategy in high-risk patients with left ventricular dysfunction.

The CORONARY trial compared OPCABG and ONCABG techniques in a large cohort (4,752 patients), including those with left ventricular dysfunction (23%). Results showed that in low-risk patients, off-pump surgery might be associated with higher one-year mortality, whereas in high-risk patients, OPCABG yielded better outcomes. This difference may be explained by the lower incidence of complications related to cardiopulmonary bypass in low-risk patients, suggesting that OPCABG could be more beneficial in medium- to high-risk patients.

Additionally, OPCABG stands out as a particularly beneficial technique for patients with significant comorbidities, such as those undergoing hemodialysis or those with diabetes and advanced vascular disease, who are at high risk for cerebrovascular complications. In these cases, the “no-touch” technique associated with OPCABG can significantly reduce postoperative complications, reinforcing its utility in high-risk populations.

In OPCABG, the use of a preoperative intra-aortic balloon pump (IABP) in patients with left ventricular dysfunction has shown benefits in high-risk patients. This device enhances cardiac performance and facilitates access to target vessels during surgery, maintaining hemodynamic stability. Known benefits of IABP include reducing ventricular afterload, improving diastolic coronary perfusion and subendocardial perfusion, and redirecting blood flow to ischemic myocardial areas. Additionally, a reduction in ventricular arrhythmias and a lower incidence of postoperative low cardiac output syndrome has been observed, helping to prevent organ dysfunction. However, the IABP is not without risks, as it can cause vascular complications, especially in certain patient groups. These complications may be mitigated by evaluating the status of the thoracic and abdominal aorta with angiography or CT scans beforehand, maintaining activated coagulation times above 150 seconds with unfractionated heparin, and shortening the IABP duration by removing it immediately after the procedure whenever possible.

Besides the use of IABP, the OPCABG technique also benefits from intracoronary shunts and CO2 blowers. Intracoronary shunts are useful for maintaining blood flow during coronary anastomosis construction, which helps prevent surgical errors. The humidified CO2 blower, on the other hand, improves the visualization of the arteriotomy, allowing for greater precision in anastomosis.

2. Hybrid Revascularization:

Hybrid coronary revascularization (HCR) combines the benefits of CABG and PCI in patients with multivessel disease. This approach is based on the proven efficacy of the LITA graft to the left anterior descending (LAD) artery via CABG, and the advantages of PCI for completing revascularization of other affected arteries in a minimally invasive manner. There are multiple approaches to HCR, but two main strategies exist: simultaneous revascularization in a hybrid operating room and staged procedures, a topic we recently discussed in previous blog posts.

Despite its potential, HCR has limitations, especially when compared to conventional CABG. Several multicenter studies and a meta-analysis indicate that, although there are no significant differences in short-term mortality between HCR and CABG, HCR may be associated with higher rates of repeat revascularization. Furthermore, long-term evidence suggests that HCR may be related to higher mortality, which could limit its utility in patients with multivessel disease over the long term.

In summary, while HCR may be a viable short-term alternative (1 year), especially when performed simultaneously, long-term results favor conventional CABG in terms of mortality and the need for reinterventions.

Graft Options for Patients with ICM

CABG is the preferred option for patients with ICM, yet there is no consensus in international guidelines on the optimal graft to maximize outcomes in these patients.

The LITA graft has proven superior to PCI in patients with severe coronary artery disease due to its better long-term patency and higher survival rates compared to saphenous vein grafts (SVGs), which are more prone to failure due to intimal fibrosis and accelerated atherosclerosis.
The use of multiple arterial grafts, such as bilateral internal thoracic artery (BITA), has shown significant survival benefits, particularly when RITA is used as a second conduit. Although BITA is not commonly used in patients with left ventricular dysfunction due to the increased technical complexity and associated risk, it offers significant benefits in reducing mortality and recurrence of cardiovascular events.
Despite these advantages, observational studies have shown contradictory results on the long-term advantage of BITA over LITA with SVG grafts. Although the ART trial found no significant differences in mortality between groups treated with BITA and LITA + SVG, potential confounding factors, such as the use of RA as a second conduit in the SITA group, high adherence to guideline-directed medical therapy, and the short follow-up period, suggest that more research is needed to determine the true value of BITA in different patient subgroups, particularly those with left ventricular dysfunction.

The use of BITA in CABG presents significant long-term benefits, but its adoption has not been universal due to the higher risk of sternal complications, such as deep wound infections and healing issues, especially in high-risk patients like the elderly, women, diabetics, and morbidly obese individuals. To mitigate these risks, the BITA skeletonization technique has been developed to preserve sternal perfusion, and strict perioperative glycemic control through intraoperative insulin infusions has been promoted.

Although CABG with BITA is generally reserved for patients under 75 years, the technique remains viable for some older patients, especially when no-touch aorta and off-pump techniques are used to reduce the risk of postoperative complications. Advanced age, diabetes, and the risk of osteoporosis and stroke are factors limiting the use of BITA, although studies have not shown significant differences in long-term survival up to 79 years.

Additionally, the use of the RA as an additional conduit in completely arterial revascularization strategies has been explored. This option is generally well tolerated, although there are contraindications for patients with upper extremity vascular disease or a history of forearm trauma. In patients with chronic kidney disease, it is important to weigh the potential benefits of using the RA against the need for future hemodialysis, as limited evidence is available on this topic.

The RA has proven to be an effective alternative to SVGs in CABG, with a lower incidence of adverse cardiac events and occlusions, as well as better patency at five years. While the RA offers an option to reduce the risk of severe sternal complications associated with BITA use, its application in patients with left ventricular dysfunction remains limited, with low representation in clinical studies. This complicates the application of findings from studies such as RAPCO and RAPS in this specific population.

Despite these limitations, the RA remains a valuable option in completely arterial revascularization strategies, with studies suggesting significant benefits in long-term survival and reduced major cardiovascular events when three arterial conduits are used instead of one or two.

Heart Failure with Improved Ejection Fraction (HFimpEF)

HFimpEF is a newly defined category recently established by the Heart Failure Society of America (HFSA), the Heart Failure Association of the European Society of Cardiology (HFA/ESC), and the Japanese Heart Failure Society (JHFS). This entity describes patients who initially presented with an LVEF ≤40% and, after treatment, achieved an LVEF greater than 40% with an increase of at least 10% from their baseline value. This improvement in LVEF has been associated in some studies with a better prognosis and a significant enhancement in health-related quality of life.

However, research on HFimpEF shows mixed results. While some studies found no significant differences in mortality between patients with HFimpEF and those with heart failure with reduced ejection fraction (HFrEF), other studies, such as a recent meta-analysis, suggest that patients with HFimpEF have a significantly lower risk of all-cause mortality, cardiac hospitalization, and composite events compared to patients with HFrEF.

Recent studies have highlighted the connection between improved LVEF and enhanced quality of life in heart failure patients. According to Wohlfart et al., each 10% increase in LVEF translates into a significant improvement in quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire. Similarly, DeVore et al. found that patients achieving an LVEF increase of ≥10% experienced a greater quality of life improvement compared to those who did not achieve this increase.

The study by Zamora et al. suggested that HFimpEF patients who showed a recovery of ventricular function tend to have a shorter duration of heart failure and belong to lower NYHA functional classes, contributing to an improved quality of life. However, quality of life is a subjective measure influenced by various factors, including comorbidities and previous hospitalizations, which should be considered when assessing patient well-being.

COMMENTARY:

Although this scoping review synthesizes the available evidence, the study acknowledges several limitations, primarily the systematic exclusion of ICM patients from most randomized controlled trials (RCTs), leading to a reliance on observational studies that may underrepresent these patients and introduce potential biases. Additionally, the lack of a universal definition for left ventricular dysfunction and the heterogeneity of reported outcomes in existing literature complicated a comprehensive evaluation of this topic.

There is an urgent need for more RCTs to properly evaluate the potential benefits of various surgical techniques and graft options in ICM patients. It is also crucial to conduct additional randomized studies exploring the clinical significance of LVEF improvements and their impact on patient-centered outcomes. An ongoing study, the MASS VI VF, is investigating this issue by comparing myocardial revascularization surgery with medical treatment in patients with multivessel coronary artery disease, angina, and severe left ventricular dysfunction, potentially providing valuable insights into optimal management for these patients.

In summary, some key conclusions from this review by section include:

• Benefits of Surgical Revascularization: Surgical revascularization has proven to be a beneficial intervention in patients with left ventricular dysfunction and an LVEF ≤35%. This intervention not only improves LVEF but is also associated with enhancements in quality of life and reductions in mortality rates, possibly linked to lower rates of repeat revascularization. These benefits are more evident in patients with demonstrated myocardial ischemia and/or angina.
• Choice of Surgical Technique: ONCABG is recommended for patients with multivessel disease, especially utilizing LITA grafts to the LAD. For older or high-risk patients, OPCABG with the “no-touch aorta” technique is a viable option that reduces the risk of cerebrovascular events.
• Considerations for Graft Selection: The risk of SVG graft occlusion suggests the need to consider a second arterial graft or even complete arterial revascularization. RITA and RA provide viable options, with techniques like skeletonization and strict perioperative glycemic control, which can mitigate risks, especially in diabetic patients.
• Need for Further Research: Despite positive findings, there is a critical need for more RCTs that include patients with left ventricular dysfunction, as most current studies are observational and present certain limitations. Additional research is also needed to explore the long-term impact of myocardial revascularization on cardiac function and clinical outcomes.
• Hybrid Revascularization: Hybrid revascularization, combining surgical grafts with percutaneous interventions, remains an option for certain patients, although clear guidelines are lacking. However, this technique could offer benefits, such as shorter hospital stays and lower costs when determined through a multidisciplinary approach.

To illustrate how some of these measures are implemented in our department at CHUAC (A Coruña), here is an overview of our general policy regarding myocardial revascularization surgery:

• OPCABG: All team members adhere to a policy of performing the majority of coronary surgeries using the OPCABG technique, achieving a rate >95% of cases and maintaining mortality below 2% over the past three years. During this technique, we perform proximal occlusion whenever possible and use shunts only when strictly necessary. The policy of consistently using OPCABG aims to train the team to handle any circumstance, not just “easy” cases. In this way, when we encounter more complex situations, such as patients with severe ventricular dysfunction, we can more likely ensure a successful surgery.
• Use of Bilateral Internal Thoracic Arteries: In more than 98% of surgeries, regardless of the patient’s age, we employ the skeletonized technique with the in situ left internal mammary artery, using the Tector technique. Routine use and constant training in this technique ensure good results, even in technically challenging cases.
• Hybrid Revascularization: Primarily applied in two specific circumstances:
  1. When there is a poor posterior descending artery bed or a proximal lesion under 90%: after surgery and if ischemia is detected during hospitalization.
  2. When revascularization of a relevant vessel cannot be achieved during surgery: performed during hospitalization prior to discharge following a Heart-Team meeting with the interventional cardiology team.
• Patients with Severe Dysfunction: We perform OPCABG and complete arterial revascularization with double mammary artery whenever the patient tolerates it. In exceptional cases, hybrid revascularization is chosen if necessary, postoperatively.

REFERENCE:

Moreno-Angarita A, Peña D, de León JDL, Estacio M, et al. Current indications and surgical strategies for myocardial revascularization in patients with left ventricular dysfunction: a scoping review. J Cardiothorac Surg. 2024 Jul 27;19(1):469. doi: 10.1186/s13019-024-02844-2.