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Treatment of ischemic cardiomyopathy

Treatment of ischemic cardiomyopathy
Literature review current through: May 2024.
This topic last updated: May 11, 2023.

INTRODUCTION — In many populations, coronary artery disease (CAD) is the most common cause of cardiomyopathy, and the term ischemic cardiomyopathy (ICM) is commonly used to describe patients with obstructive CAD and a left ventricular ejection fraction (LVEF) <40 percent, but there is no consensus or formal definition. The optimal treatment of patients with ICM requires management of multiple conditions that include CAD, heart failure (HF) with reduced ejection fraction, and the common complications of cardiomyopathy (eg, arrhythmias, chronic kidney disease).

This topic will discuss the treatment of patients with ICM with a focus on the approach to revascularization [1,2].

The clinical manifestations and diagnosis of HF, the approach to determining the cause of cardiomyopathy, and the prognosis of patients with ICM are discussed separately:

(See "Heart failure: Clinical manifestations and diagnosis in adults".)

(See "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Determining the cause and severity of heart failure or cardiomyopathy'.)

(See "Prognosis of heart failure".)

GOALS OF THERAPY — In patients with ICM, the goals of therapy are to prolong survival, improve quality of life, and reduce the risk of acute cardiac (eg, ventricular tachycardia, repeat myocardial infarction [MI]) and noncardiac complications (eg, chronic kidney disease).

Because obstructive CAD is a potentially reversible cause of cardiomyopathy, another goal of therapy is to improve ventricular function.

OVERVIEW OF TREATMENT — The management of patients with ICM includes the following:

Treatment of obstructive CAD In patients with ICM, obstructive CAD is a potentially reversible cause of cardiomyopathy, and, accordingly, its management should be a priority. The approach to revascularization in patients with ICM requires a detailed assessment to determine the risks and benefits of coronary artery bypass graft surgery, percutaneous coronary intervention, or continued goal-directed medical therapy without revascularization. (See 'Approach to revascularization' below.)

Management of symptoms – Patients with ICM require management of symptoms such as angina, congestion, and dyspnea. However, the approach to the management of angina in patients with ICM is different from the management of patients with isolated CAD. In patients with ICM, angina often responds to the treatment of HF, and, similarly, HF may respond to treatment of CAD. (See 'Management of angina and heart failure' below.)

Long-term therapy for CAD and ventricular dysfunction Patients with ICM should receive preventive therapies that reduce the risk of acute MI and slow the progression of CAD. In addition, patients with ICM should receive optimal therapy for LV dysfunction and HF. (See 'Preventive therapies for CAD' below and 'Management of angina and heart failure' below.)

Specialized therapy for complications – In patients with ICM, the presence of CAD may alter the management of conditions such as atrial fibrillation and ventricular tachycardia. In addition, patients with ICM can develop unique complications that require specialized management (eg, LV aneurysm, ischemic mitral regurgitation). (See 'Complications that require specialized care' below.)

APPROACH TO REVASCULARIZATION

Who should undergo revascularization? — All patients with ICM should undergo evaluation for revascularization. In combination with optimal medical therapy (table 1 and table 2), revascularization has the potential to improve survival in patients with ICM despite the increased risks associated with revascularization. (See 'Choosing CABG, PCI, or no revascularization' below.)

In patients with ICM, common clinical scenarios that should initiate an evaluation for revascularization include:

Patients with newly diagnosed ICM – Regardless of the presence or absence of symptoms attributable to ischemia, patients with newly diagnosed HF with reduced ejection fraction (HFrEF) should undergo an evaluation for obstructive CAD and appropriate revascularization.

Patients with chronic ICM with new signs or symptoms of ischemia – Patients with ICM who have new signs or symptoms that are likely caused by ischemia should undergo evaluation and appropriate revascularization. In patients with ICM, signs and symptoms that may represent progressive CAD include:

Decrease in LVEF more than 5 to 10 percent

New ventricular arrhythmias

New and unexplained exertional chest discomfort or dyspnea

Worsening angina or recurrence of the patient’s anginal equivalent

Pretreatment evaluation — In patients with ICM who receive optimal medical therapy (eg, appropriate decongestion, guideline-directed medical therapy) (table 1 and table 2), coronary artery revascularization has the potential to reverse or slow the effects of ischemia on the myocardium (eg, symptoms, LV dysfunction) and prevent recurrent MI. However, revascularization may not be safe or effective due to the presence of severe HF, advanced comorbid conditions (eg, kidney disease), diffuse coronary disease, or irreversible myocardial injury. Thus, a thorough pretreatment evaluation is required to determine the risks and benefits of coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), or continued medical therapy without revascularization. This evaluation includes:

Clinical assessment — Patients under evaluation for revascularization should be assessed for the presence and severity of conditions that may alter the risk or benefit of revascularization. The assessment of each condition includes an appropriate history, physical examination, laboratory testing, and imaging. The findings from the clinical assessment are used to determine the risks of revascularization and, in particular, the risk of CABG. The approach to evaluation prior to cardiac surgery can be found elsewhere. (See "Preoperative evaluation for anesthesia for cardiac surgery".)

The approach to surgical risk estimation for patients with ICM is discussed elsewhere in this topic. (See 'Surgical risk estimation' below.)

Echocardiography — If not recently performed, patients with ICM should undergo transthoracic echocardiography as part of the evaluation for revascularization. Echocardiography provides general information that may influence the prognosis, risk of revascularization, or approach to surgery (eg, simultaneous valve surgery).

Surgical risk estimation — Patients with ICM often have multiple comorbidities that increase the risk of CABG, and the risk of CABG directly influences the choice of revascularization (see 'Choosing CABG, PCI, or no revascularization' below). Thus, all patients with ICM under consideration for revascularization should have an assessment of their surgical risk as part of the pretreatment evaluation.

When estimating the risk of CABG, we assess the patient’s general clinical condition and use a risk score to estimate the overall risk as follows:

General assessment – Each patient undergoing evaluation for revascularization should be assessed for factors that significantly affect surgical risk but may not be captured by risk scores. There are no robust methods for evaluating these risk factors; clinical judgement and experience determine whether these factors increase the risk of CABG above an acceptable threshold. We typically assess the following:

Nutritional status (eg, cachexia, serum prealbumin levels)

Presence of other disorders that limit life expectancy (eg, untreatable cancer, advanced lung disease)

Ability to participate in rehabilitation (eg, physical therapy assessment)

Ability to comply with optimal medical therapy

Presence of appropriate vascular conduits for CABG

Contraindications to anticoagulation (eg, recent surgery, history of intracerebral hemorrhage)

Risk score estimate – We typically use the Society of Thoracic Surgeons (STS) Score or the EuroScore-2 to calculate the 30-day risk of postoperative mortality for CABG. The use of a risk score to determine the risk of CABG is endorsed by the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) guideline for coronary artery revascularization, though the guideline provides no guidance on how to use a risk score [3].

Both scores estimate the 30-day risk of mortality and have acceptable accuracy [4-6]. However, patients with cardiomyopathy are typically underrepresented in the data, and patients who did not undergo CABG as the result of excessive risk were not included in the creation or validation of these risk models. Accordingly, the estimated risk may be an underestimate of actual risk for patients with ICM or those who have high risk scores.

Determining the overall surgical risk – After performing a general assessment and calculating the 30-day risk of mortality for CABG, we estimate the overall risk of CABG. We consider patients at "high risk" if their general assessment identifies contraindications to surgery or if their 30-day risk of postoperative mortality, as determined by the aggregate results of testing, is more than 10 percent.

There is no objective threshold for "high" surgical risk. Thus, some contributors to this topic do not favor the use of any specific benchmark, while other contributors to this topic use data on the benefit of CABG and from the STICH trial as benchmarks for high risk [7]. Data from the STICH trial that indirectly address thresholds for risk include:

In patients enrolled in the STICH trial, the median STS risk of 30-day mortality was 0.9 percent (interquartile range [IQR] 0.6-1.6 percent) and the median EuroScore-2 risk of mortality was 2.4 percent (IQR 1.5-3.8 percent) [8].

Among patients in the STICH trial randomly assigned to CABG, the observed 30-day mortality was 4 percent [9].

Surgeons in the STICH trial were required to submit evidence that their operative mortality for at least 25 patients with an LVEF ≤40 percent was not more than 5 percent [7].

Coronary angiography — Patients with newly diagnosed ICM will typically have an invasive coronary angiogram as part of the initial evaluation for cardiomyopathy, though some studies suggest assessment for CAD is underutilized [10,11]. Most patients who do not have a recent angiogram should undergo invasive coronary angiography to assess for the presence of obstructive CAD amenable to revascularization. In rare cases, coronary angiography may not be required. These scenarios include:

Patients who cannot undergo revascularization due to the presence of conditions such as multisystem organ failure or another life-threatening illness (eg, acute respiratory distress syndrome).

Patients in whom the coronary anatomy is reasonably well-known but in whom revascularization is unlikely to be beneficial (eg, ischemia in regions not amenable to revascularization, patients with chronic ICM and refractory HF). In such cases, the treating cardiologist and/or cardiac surgeon typically decide whether angiography is necessary.

The angiogram is used to identify coronary artery stenoses amenable to revascularization. For patients with ICM, we use the standard definitions for flow-limiting coronary artery stenosis (ie, epicardial coronary artery stenosis ≥70 percent, left main coronary artery stenosis ≥50 percent). If the degree of coronary artery stenosis is unclear, stress imaging or intracoronary pressure wire measurements may be used to determine the severity of stenosis on a case-by-case basis. (See 'Additional imaging' below and "Clinical use of coronary artery pressure flow measurements".)

Additional imaging — Additional imaging may influence the optimal approach to revascularization and/or be used to select territories for revascularization.

Role of viability testing – Patients who have regions of severe myocardial dysfunction (eg, regional wall thinning, akinesis, dyskinesis) and/or infarction that exhibit viability (ie, have residual metabolic activity) may recover some function if blood flow to those regions is restored [1,12]. In patients with ICM who have imaging evidence of MI (ie, infarction) with severe myocardial dysfunction (eg, akinesis, dyskinesis) and/or adverse remodeling (eg, thinning, aneurysm, scar), the decision to perform a viability test is individualized, while in patients with ICM who have none of these features (ie, low suspicion for myocardial scar), viability testing is not indicated.

The ACC/AHA/SCAI guideline for coronary artery revascularization has no specific recommendation for or against viability testing [3].

Additional factors that influence the utility of viability testing include:

Factors that favor the use of viability testing – In patients with either of the following factors, the presence or absence of viability may influence the benefit of revascularization:

-Patients with moderate to large areas of infarction in territories amenable to revascularization

-Patients in whom the risk of CABG or PCI is high and the benefit of surgery is unclear

Factors that suggest that viability testing may not be useful – In patients with the following factors, viability testing is unlikely to influence the benefit of revascularization:

-Patients in whom the dominant presentation is angina.

-Patients with only small areas of infarction in territories amenable to revascularization.

-Patients at high risk for CABG or PCI by other criteria (eg, patients with New York Heart Association [NYHA] class IV symptoms or severe chronic kidney disease); these patients are likely unsuitable for revascularization despite the presence of viable segments.

The options for viability testing and the relative merits of each viability testing modality are discussed elsewhere. (See "Evaluation of hibernating myocardium".)

There are no high-quality studies to suggest that revascularization guided by viability improves survival, and observational studies disagree on the utility of viability testing and are limited by bias [1,12]:

In the REVIVED trial, patients with an LVEF of ≤35 percent who had a moderate to large region of viable myocardium and who were assigned to medical therapy or PCI had similar rates of mortality and rehospitalization [13]. While this finding may have been the result of a less effective method of revascularization (ie, PCI relative to CABG) or selection bias, it is also reasonable to conclude that viability testing may not identify patients with ICM who benefit from revascularization. The details of this trial are discussed elsewhere in this topic. (See 'Patients who cannot undergo cardiac surgery' below.)

In the only trial of viability-guided management, the PPAR-2 trial, 430 patients with severe LV dysfunction were randomly assigned to management assisted by fluorodeoxyglucose-positron emission tomography (FDG-PET) or standard care [14]. At one year, the cumulative proportion of patients who experienced the primary endpoint (composite of cardiac death, MI, or hospitalization for cardiac cause) was similar between groups (30 versus 36 percent in the standard of care arm; hazard ratio [HR] 0.78, 95% CI 0.58-1.1). Notably, 25 percent of the patients did not receive management consistent with their viability test results. In a secondary analysis of the trial's data that was not prespecified, patients who were assigned to management with PET and whose providers followed the protocol for imaging-guided revascularization had a lower risk of mortality (HR 0.62, 95% CI 0.42-0.93). Overall, the high prevalence of protocol deviations limits the external validity and clinical translation of the trial’s results.

In a substudy of the STICH trial, 601 patients who had a viability study were assigned to randomly receive either CABG or medical therapy [15]. Patients with viable myocardium who were randomly assigned to CABG had higher 10-year survival than those assigned to medical therapy alone (70 versus 60 percent; HR 0.7, 95% CI 0.56-0.88), while patients without viability who were randomly assigned to CABG had nonsignificant higher survival than those assigned to medical therapy alone (72 versus 67 percent; HR 0.81, 95% CI 0.5-1.3). Overall, this study suggests that presence or absence of viability did not affect the benefit of CABG, which favored surgery as described in the main results of the STICH trial. (See 'Patients who can undergo cardiac surgery' below.)

The strengths of this study include the prospective collection of data and large sample size. Its limitations include a nonstandard approach to viability testing, which was at the discretion of the treating clinician, testing of a hypothesis that was not prespecified, and use of older imaging technologies to assess viability.

Similar to the result of the STICH viability study, a study of patients with LV dysfunction suggested that early revascularization may be of benefit to patients regardless of the presence or absence of viability (propensity-adjusted odds ratio 0.52, 95% CI 0.33-0.81) [16]. While the propensity method may attenuate selection bias, the study’s findings are not definitive.

A meta-analysis of 3088 patients from 24 observational studies reported that among patients with viability, revascularization was associated with a lower risk of mortality when compared with medical therapy (3 versus 16 percent per year) [17]. Patients without significant viability had similar mortality rates regardless of whether they were revascularized or not (8 versus 6 percent per year). However, each of the component studies in the meta-analysis were subject to bias that limits the generalizability of these findings.

In an analysis that pooled surrogate outcomes, there was a mean increase in LVEF of approximately 8 percent after revascularization when hibernating myocardium was present (37 versus 45 percent) compared with no change in the absence of hibernation (36 versus 37 percent) [18].

Role of stress imaging – Stress imaging may be used to help determine the cause of symptoms or to identify regions of the myocardium where revascularization is likely to be beneficial (ie, regions with significant severity and extent of ischemia). In patients with chest symptoms of unclear etiology, the presence of a moderate to large area of ischemic myocardium may help to determine whether ischemia or progressive pump dysfunction is more likely.

Stress imaging may be of particular benefit in patients with complex CAD (eg, known occlusions, multiple prior attempts at revascularization) to determine whether significant ischemia exists in a coronary distribution amenable to revascularization, or in patients in whom the risks of CABG (or, less commonly, PCI) are particularly high. In such patients, the use of stress imaging to guide revascularization is individualized.

Choosing CABG, PCI, or no revascularization — The choice of CABG, PCI, or no revascularization should be determined using a patient-centered approach that incorporates the risks and benefits of each revascularization strategy (algorithm 1). All patients with ICM should be evaluated by an interdisciplinary team (ie, heart team) to determine the relative risks and benefits of revascularization and alternatives to revascularization, such as continued medical therapy without revascularization, heart transplantation, or mechanical circulatory support. Ideally, the evaluation for revascularization should occur after optimization of the patient’s other HFrEF therapies (eg, diuretics, neurohormonal therapies) [3].

One of the primary tasks of an interdisciplinary team is to determine the benefits and risks of the available treatment options. The use of several general principles (see 'General principles' below) may influence the approach to revascularization, but, in broad terms, the approach is typically determined by the risk of CABG (see 'Surgical risk estimation' above), as follows:

General principles — The approach to revascularization may be influenced by the results of viability testing, the severity of LV dysfunction, the risks and benefits of advanced HF therapies (eg, transplantation, mechanical support) relative to revascularization or medical therapy, and the experience with revascularization. However, the contributors to this topic have different views on how to incorporate these findings, tests, and the risks and benefits of alternative therapies into the overall approach to revascularization. The contributors to this topic agree that there is no standard method for considering these factors, but we strongly favor a multidisciplinary approach (ie, heart team discussion) [3].

Patients who can undergo cardiac surgery — In patients with ICM who are acceptable candidates for CABG surgery and who have NYHA class I to III HF symptoms, angina, or LV dysfunction that is likely due to CAD, the choice of CABG, PCI, or no attempt at revascularization is determined by the location and extent of CAD and whether the specific vessels are amenable to CABG or PCI (ie, grafting or stenting is technically feasible) (algorithm 1):

Multivessel disease or its equivalent – In patients with signs or symptoms of obstructive CAD and multivessel (ie, two- or three-vessel) or left main CAD (ie, ≥50 percent stenosis of the left main coronary artery or ≥70 percent stenosis of the proximal left anterior descending coronary artery and proximal left circumflex disease), we suggest revascularization with CABG rather than PCI or no attempt at revascularization (algorithm 1).

In patients who decide not to undergo CABG, reasonable options include no revascularization or PCI; the approach is determined by an interdisciplinary team and may be influenced by other factors. (See 'General principles' above.)

Our preference for CABG in this group of patients is based on the benefits of CABG relative to PCI or no revascularization described in trials of patients with multivessel disease and either normal or low LVEF. However, in the broader set of trials that compared the efficacy of CABG with PCI and found CABG to be superior to PCI, few patients with severe LV dysfunction were included. There are no trials of revascularization in patients with ICM who were treated with optimal modern medical therapy. As such, our approach to patients who are optimally managed with HFrEF therapies is based on an aggregate of indirect evidence that suggests that CABG is typically superior to PCI and to medical therapy alone. The available data include:

In a meta-analysis of patients (n = 11,518) with multivessel or left main CAD enrolled in trials that compared CABG with PCI, patients randomly assigned to CABG had a lower risk of all-cause mortality at five years (9 versus 11 percent; HR 0.83, 95% CI 0.71-0.91) [19]. In the subgroup of patients with an LVEF 30 to 49 percent (n = 1586), revascularization with CABG was also associated with a lower risk of mortality (15 versus 19 percent; HR 0.71, 95% CI 0.52-0.93). In the small subgroup of patients with an LVEF less than 30 percent (n = 103), there was less certainty of a benefit with CABG (34 versus 57 percent in the PCI group; HR 0.8, 95% CI 0.4-1.6).

In the STICH trial and its long-term follow-up study (STICHES), 1212 patients with ICM and an LVEF less than 35 percent were randomly assigned to receive CABG with optimal medical therapy or optimal medical therapy alone [7]. The majority of the patients enrolled had NYHA class I to III HF symptoms. The trial design included features that assured a high standard of care: The participating surgeons had to demonstrate less than 5 percent mortality in 25 patients with LVEF <40 percent, and the medical management of all patients was supervised by trial leadership. Among patients who received CABG in the trial, 91 percent received at least one arterial bypass graft, and 87 percent had bypass of two or more vessels. In this context, patients randomly assigned to CABG had a lower 10-year risk of all-cause mortality (59 versus 66 percent; HR 0.84, 95% CI 0.73-0.97) [9]. The standards for medical therapy in this trial did not include modern medications (eg, sacubitril-valsartan, sodium-glucose co-transporter 2 inhibitors).

The REVIVED trial suggested that optimal medical therapy alone and PCI with optimal medical therapy have similar effects on mortality [13]. However, it is unclear whether the patients enrolled in this trial were eligible for cardiac surgery. This trial is discussed elsewhere in this topic. (See 'Patients who cannot undergo cardiac surgery' below.)

Single vessel disease – In patients with signs (eg, inducible ischemia, decrease in LVEF) or symptoms (eg, worsening angina or HF) attributable to single-vessel CAD, we suggest single-vessel PCI rather than single-vessel CABG or no attempt at revascularization (algorithm 1).

In our experience, the benefit to risk ratio of single-vessel PCI is likely greater than the benefit to risk ratio of single-vessel CABG or no attempt at revascularization, but the benefit of single-vessel PCI versus no attempt at revascularization may be small. The expert contributors to this topic agree that ICM is rarely caused by single-vessel disease, though progression of CAD in a single vessel can occur in patients with ICM. There are no high-quality data that describe the relative benefit of single-vessel PCI, single-vessel CABG, or optimal modern medical therapy; few patients with single-vessel disease and reduced LVEF were included in trials of revascularization, and the available trials predate modern medical therapy.

Patients who cannot undergo cardiac surgery — In patients with ICM who cannot undergo CABG surgery due to the presence of high-risk features (eg, NYHA class IV symptoms, severe kidney disease), the decision to perform PCI or to continue medical therapy without PCI depends on the benefit of revascularization (see 'General principles' above) and the risk of PCI (algorithm 1):

In patients who have signs or symptoms of obstructive CAD (eg, angina, decrease in LV systolic function) or evidence of a moderate to large area of inducible ischemia and in whom the risk of PCI is acceptable, we suggest PCI.

In patients without a clear association between obstructive CAD and signs or symptoms of ICM or who have an unacceptably high risk of complications with PCI, we continue optimal medical therapy.

In patients with NYHA class IV symptoms, the risks and benefits of revascularization should be compared with the risks and benefits of advanced HF therapies. The options for the treatment of advanced HF are discussed separately. (See "Management of refractory heart failure with reduced ejection fraction" and "Management of refractory heart failure with reduced ejection fraction", section on 'Components of therapy'.)

If additional management results in an acceptable risk for cardiac surgery (eg, improved NYHA class), the risks and benefits of revascularization should be readdressed, as discussed elsewhere in this topic. (See 'Patients who can undergo cardiac surgery' above.)

In patients with ICM who cannot undergo cardiac surgery, the benefits of revascularization with PCI are largely unknown. The efficacy of revascularization in patients with evidence of ischemia is not well-studied; based on our experience, we believe that revascularization in this group of patients may result in fewer symptoms and less ischemic injury to the myocardium. In patients who are not candidates for CABG surgery and who do not have evidence of inducible ischemia, there are few studies that directly address the efficacy of revascularization. However, indirect data suggest that PCI may not have a benefit when compared with medical therapy alone:

In the REVIVED trial that included 700 patients with ICM with an LVEF ≤35 percent and who had myocardial viability in at least four segments of myocardium (over 50 percent had multivessel disease) amenable to revascularization, patients randomly assigned to PCI and optimal medical therapy or to optimal medical therapy alone had similar rates of death or hospitalization after a median of 3.4 years of observation (37 versus 38 percent in the optimal medical therapy group; HR 0.99, 95% CI 0.78-1.27) [13]. In addition, the average LVEF was similar between the two groups 12 months after randomization (mean difference -1.6 percent; 95% CI -3.7 to 0.5 percent). The study did not have a CABG arm and did not report on the feasibility of CABG amongst the patients enrolled. In addition, the severity of HF among those enrolled was unclear, and the study included some patients (approximately 33 percent) with angina. For the latter, we would typically revascularize such patients if medical therapy had failed. These factors limit the trial’s broad application to patients with ICM typically encountered in practice.

Assessing the response to revascularization — We typically assess the response to revascularization with clinical evaluation (eg, improvement in symptoms) and echocardiography within three months of revascularization. We do not routinely repeat stress imaging to assess for residual ischemia after revascularization; we only repeat an ischemic evaluation if there is a high suspicion for residual ischemia.

PREVENTIVE THERAPIES FOR CAD — Patients with ICM should receive treatment to mitigate the progression of CAD and reduce the risk of acute coronary syndrome (ie, secondary prevention) similar to other patients with CAD. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

MANAGEMENT OF ANGINA AND HEART FAILURE

Treatment of angina — In patients with ICM who are optimally revascularized and treated for volume overload but who continue to have anginal symptoms, we use the following approach to treat angina, which is based on our clinical experience:

Optimize medical therapy for HF with reduced ejection fraction – In patients with ICM who have angina, the first step in treatment is to relieve congestion and optimize therapy with medications that reduce mortality in patients with HF with reduced ejection fraction (HFrEF):

Initial therapy with beta blockers – Beta blockers have antianginal effects and reduce mortality in patients with HFrEF. Thus, patients with angina and HFrEF who can tolerate a lower blood pressure should undergo initial optimization of beta blocker therapy before adjusting the dose of other medications used to treat HFrEF and before adding antianginal agents (eg, calcium channel blockers, ranolazine). The target doses and precautions for beta blocker therapy in patients with HFrEF are described elsewhere (table 1). (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker'.)

Patients with residual angina after beta blocker optimization – If optimal beta blocker therapy does not treat the patient’s angina and the patient can tolerate a lower blood pressure, we typically increase doses of vasodilator agents (eg, sacubitril-valsartan, angiotensin converting enzyme inhibitors) to their target dose as tolerated (table 1). If these changes do not adequately treat the patient’s symptoms, we then treat with secondary therapies for HFrEF (eg, hydralazine-isosorbide dinitrate) as tolerated (table 2). The dosing and precautions for these agents are discussed elsewhere. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction" and "Secondary pharmacologic therapy for heart failure with reduced ejection fraction".)

Patients with residual symptoms In patients who are intolerant or refractory to medical therapy with agents used to treat HFrEF (eg, beta blockers, sacubitril-valsartan, isosorbide dinitrate), antianginal therapy is indicated. The initial choice of therapy is often determined by the patient’s blood pressure:

Patients with hypotension or normotension – Hypotension can cause angina or be a sign of either advanced ischemia or advanced HF and warrants an evaluation before focusing on symptom treatment. However, in patients with confirmed angina and stable CAD who have either hypotension or normotension, ranolazine can be used to treat angina. Ranolazine has minimal or no effect on blood pressure. The details on ranolazine therapy are discussed elsewhere. (See "New therapies for angina pectoris", section on 'Ranolazine'.)

Patients with hypertension – In patients with residual hypertension despite titration of HF medications to their highest tolerated or optimal doses, the second-generation dihydropyridines (amlodipine, felodipine) can be used to reduce blood pressure and treat angina. These agents are typically started at their lowest dose and increased as tolerated and as needed to achieve symptom relief.

Nondihydropyridine calcium channel blockers (eg, diltiazem) have negative inotropic effects and should not be used in patients with ICM. Further information on the use of calcium-channel blockers in patients with HFrEF can be found elsewhere. (See "Major side effects and safety of calcium channel blockers", section on 'Use in heart failure and coronary artery disease'.)

Treatment of heart failure — Patients with ICM should be appropriately treated with pharmacologic and device therapies that improve survival and quality of life:

Pharmacologic therapy – In patients with ICM who have decompensated HF, the approach to treatment is similar to patients with other types of HFrEF, except the progression of CAD should be considered a possible cause of decompensation in patients with ICM. Therapies for patients with ICM and New York Heart Association (NYHA) class II to III HF symptoms typically include a diuretic to treat volume overload and medications that reduce the risk of mortality and hospitalization. These therapies are discussed in detail elsewhere. (See "Use of diuretics in patients with heart failure" and "Overview of the management of heart failure with reduced ejection fraction in adults", section on 'Pharmacologic therapy'.)

Pharmacologic therapy for patients with ICM who have NYHA class I HF symptoms or no HF symptoms is discussed separately. (See "Management and prognosis of asymptomatic left ventricular systolic dysfunction".)

Cardiac implantable electronic device therapy In patients with ICM, an implantable cardioverter-defibrillator (ICD) and/or cardiac resynchronization therapy (CRT) pacemaker may be indicated. The indications for implantation of an ICD and/or CRT pacemaker are discussed separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Cardiac resynchronization therapy in systolic heart failure: Indications and choice of system".)

COMPLICATIONS THAT REQUIRE SPECIALIZED CARE — In patients with ICM who have advanced HF or valve disease, additional management is required, while patients with ICM and arrhythmias or LV aneurysm require a unique approach to management.

Advanced heart failure — In patients who have New York Heart Association class IV HF symptoms despite optimal therapy or other features of advanced HF, the approach to management requires an assessment for advanced HF therapies such as mechanical circulatory support therapy, cardiac transplantation, and palliative care. The diagnosis and management of patients with advanced HF are discussed separately. (See "Clinical manifestations and diagnosis of advanced heart failure" and "Management of refractory heart failure with reduced ejection fraction".)

Valve disease — Patients with ICM are at risk of mitral regurgitation as the result of ventricular dilation or ongoing ischemia that affects a papillary muscle. The diagnosis and management of mitral regurgitation are discussed elsewhere. (See "Chronic secondary mitral regurgitation: General management and prognosis" and "Acute mitral regurgitation in adults", section on 'Ischemic MR'.)

Arrhythmias — In patients with ICM, the approach to the management of arrhythmias is similar to other patients who have either HF or CAD. The details of arrhythmia management in such patients can be found elsewhere. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy" and "The management of atrial fibrillation in patients with heart failure".)

Left ventricular aneurysm — Patients with ICM may develop an LV aneurysm or pseudoaneurysm, which require specific management. The diagnosis and management of patients with an LV aneurysm are discussed elsewhere. (See "Left ventricular aneurysm and pseudoaneurysm following acute myocardial infarction".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Chronic coronary syndrome" and "Society guideline links: Percutaneous coronary intervention" and "Society guideline links: Coronary artery bypass graft surgery" and "Society guideline links: Multimodality cardiovascular imaging appropriate use criteria" and "Society guideline links: Stress testing and cardiopulmonary exercise testing".)

SUMMARY AND RECOMMENDATIONS

Approach to revascularization

Who should undergo revascularization? – All patients with ischemic cardiomyopathy (ICM) should undergo evaluation for revascularization. In combination with optimal medical therapy (table 1 and table 2), revascularization has the potential to improve survival despite the higher risks associated with revascularization in patients with reduced left ventricular ejection fraction (LVEF). (See 'Who should undergo revascularization?' above.)

Pretreatment evaluation – Revascularization may not be safe or effective due to the presence of severe heart failure (HF), advanced comorbid conditions (eg, kidney disease), diffuse coronary disease, or irreversible myocardial injury. Thus, a thorough pretreatment evaluation is required to determine the risks and benefits of coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), or continued medical therapy without revascularization. (See 'Pretreatment evaluation' above.)

The components of the pretreatment evaluation include:

-Clinical assessment – Patients under evaluation for revascularization should be assessed for the presence and severity of conditions that may alter the risk or benefit of revascularization. The assessment of each condition includes an appropriate history, physical examination, laboratory testing, and imaging. (See 'Clinical assessment' above.)

-Echocardiography – If not recently performed, patients with ICM should undergo echocardiography as part of the evaluation for revascularization. (See 'Echocardiography' above.)

-Surgical risk estimation – Patients with ICM typically have multiple comorbidities that increase the risk of CABG, and the risk of CABG directly influences the choice of revascularization. (See 'Surgical risk estimation' above.)

-Coronary angiography – Most patients who do not have a recent angiogram should undergo invasive coronary angiography to assess for the presence of obstructive coronary artery disease (CAD) amenable to revascularization. (See 'Coronary angiography' above.)

-Additional imaging – In patients with ICM in whom the risk of surgery is relatively high and the benefit is unclear, additional imaging may be helpful to further inform decision making. (See 'Additional imaging' above and 'General principles' above.)

Choosing CABG, PCI, or no revascularization – The choice of CABG, PCI, or no revascularization should be determined using a patient-centered approach that incorporates the risks and benefits of each revascularization strategy (algorithm 1). (See 'Choosing CABG, PCI, or no revascularization' above and 'Surgical risk estimation' above.)

-General principles – The approach to revascularization may be influenced by the results of viability testing, the severity of LV dysfunction, the risks and benefits of advanced HF therapies (eg, transplantation, mechanical support) relative to revascularization or medical therapy, and the experience with revascularization. (See 'General principles' above.)

-Patients who can undergo cardiac surgery – In patients with ICM who are acceptable candidates for CABG surgery and who have New York Heart Association (NYHA) class I to III HF symptoms, angina, or LV dysfunction that is likely due to CAD, the choice of CABG, PCI, or no attempt at revascularization is determined by the location and extent of CAD and whether the specific vessels are amenable to CABG or PCI (ie, grafting or stenting is technically feasible) (see 'Patients who can undergo cardiac surgery' above):

In patients with multivessel disease or its equivalent, we suggest revascularization with CABG rather than PCI or no attempt at revascularization (algorithm 1) (Grade 2B).

In patients with single-vessel CAD, we suggest single-vessel PCI rather than single-vessel CABG or no attempt at revascularization (algorithm 1) (Grade 2C). In our experience, the benefit to risk ratio of single-vessel PCI is likely greater than the benefit to risk ratio of single-vessel CABG or no attempt at revascularization, but the benefit of single-vessel PCI versus no attempt at revascularization may be small.

-Patients who cannot undergo cardiac surgery – In patients with ICM who cannot undergo CABG surgery due to the presence of high-risk features (eg, NYHA class IV symptoms, severe kidney disease), the decision to perform PCI or to continue medical therapy without PCI depends on the benefit of revascularization and the risk of PCI (see 'Patients who cannot undergo cardiac surgery' above):

In patients who have signs or symptoms of obstructive CAD (eg, angina, decrease in LV systolic function) or evidence of a moderate to large area of inducible ischemia and in whom the risk of PCI is acceptable, we suggest PCI (algorithm 1) (Grade 2C).

In patients without a clear association between obstructive CAD and signs or symptoms of ICM or who have an unacceptably high risk of complications with PCI, we suggest continuing optimal medical therapy and not performing PCI (algorithm 1) (Grade 2C).

Preventive therapies and management of symptoms

Treatment of angina – In patients with ICM, the approach to the treatment of angina is different than in patients with angina who do not have a cardiomyopathy; patients with ICM should have optimal use of medications used to treat HF with reduced ejection fraction (HFrEF) before using antianginal therapies. (See 'Treatment of angina' above.)

Treatment of heart failure – In patients with ICM who have decompensated HF, the approach to treatment is similar to patients with other types of HFrEF, except the progression of CAD is a possible cause of decompensation in patients with ICM. (See 'Treatment of heart failure' above.)

Complications that require specialized care – In patients with ICM who have advanced HF or valve disease, additional management is required, while patients with ICM and arrhythmias or LV aneurysm require a unique approach to management. (See 'Complications that require specialized care' above.)

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Topic 1507 Version 39.0

References

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