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Study 1 Overview (STICHES Investigators)
Objective: To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical therapy (OMT) alone, in patients with coronary artery disease, heart failure, and severe left ventricular dysfunction. Design: Multicenter, randomized, prospective study with extended follow-up (median duration of 9.8 years).
Setting and participants: A total of 1212 patients with left ventricular ejection fraction (LVEF) of 35% or less and coronary artery disease were randomized to medical therapy plus CABG or OMT alone at 127 clinical sites in 26 countries.
Main outcome measures: The primary endpoint was death from any cause. Main secondary endpoints were death from cardiovascular causes and a composite outcome of death from any cause or hospitalization for cardiovascular causes.
Main results: There were 359 primary outcome all-cause deaths (58.9%) in the CABG group and 398 (66.1%) in the medical therapy group (hazard ratio [HR], 0.84; 95% CI, 0.73-0.97; P = .02). Death from cardiovascular causes was reported in 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical therapy group (HR, 0.79; 95% CI, 0.66-0.93; P < .01). The composite outcome of death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and 467 patients (87.0%) in the medical therapy group (HR, 0.72; 95% CI, 0.64-0.82; P < .01).
Conclusion: Over a median follow-up of 9.8 years in patients with ischemic cardiomyopathy with severely reduced ejection fraction, the rates of death from any cause, death from cardiovascular causes, and the composite of death from any cause or hospitalization for cardiovascular causes were significantly lower in patients undergoing CABG than in patients receiving medical therapy alone.
Study 2 Overview (REVIVED BCIS Trial Group)
Objective: To assess whether percutaneous coronary intervention (PCI) can improve survival and left ventricular function in patients with severe left ventricular systolic dysfunction as compared to OMT alone.
Design: Multicenter, randomized, prospective study.
Setting and participants: A total of 700 patients with LVEF <35% with severe coronary artery disease amendable to PCI and demonstrable myocardial viability were randomly assigned to either PCI plus optimal medical therapy (PCI group) or OMT alone (OMT group).
Main outcome measures: The primary outcome was death from any cause or hospitalization for heart failure. The main secondary outcomes were LVEF at 6 and 12 months and quality of life (QOL) scores.
Main results: Over a median follow-up of 41 months, the primary outcome was reported in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the OMT group (HR, 0.99; 95% CI, 0.78-1.27; P = .96). The LVEF was similar in the 2 groups at 6 months (mean difference, –1.6 percentage points; 95% CI, –3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, –1.7 to 3.4). QOL scores at 6 and 12 months favored the PCI group, but the difference had diminished at 24 months.
Conclusion: In patients with severe ischemic cardiomyopathy, revascularization by PCI in addition to OMT did not result in a lower incidence of death from any cause or hospitalization from heart failure.
Commentary
Coronary artery disease is the most common cause of heart failure with reduced ejection fraction and an important cause of mortality.1 Patients with ischemic cardiomyopathy with reduced ejection fraction are often considered for revascularization in addition to OMT and device therapies. Although there have been multiple retrospective studies and registries suggesting that cardiac outcomes and LVEF improve with revascularization, the number of large-scale prospective studies that assessed this clinical question and randomized patients to revascularization plus OMT compared to OMT alone has been limited.
In the Surgical Treatment for Ischemic Heart Failure (STICH) study,2,3 eligible patients had coronary artery disease amendable to CABG and a LVEF of 35% or less. Patients (N = 1212) were randomly assigned to CABG plus OMT or OMT alone between July 2002 and May 2007. The original study, with a median follow-up of 5 years, did not show survival benefit, but the investigators reported that the primary outcome of death from any cause was significantly lower in the CABG group compared to OMT alone when follow-up of the same study population was extended to 9.8 years (58.9% vs 66.1%, P = .02). The findings from this study led to a class I guideline recommendation of CABG over medical therapy in patients with multivessel disease and low ejection fraction.4
Since the STICH trial was designed, there have been significant improvements in devices and techniques used for PCI, and the procedure is now widely performed in patients with multivessel disease.5 The advantages of PCI over CABG include shorter recovery times and lower risk of immediate complications. In this context, the recently reported Revascularization for Ischemic Ventricular Dysfunction (REVIVED) study assessed clinical outcomes in patients with severe coronary artery disease and reduced ejection fraction by randomizing patients to either PCI with OMT or OMT alone.6 At a median follow-up of 3.5 years, the investigators found no difference in the primary outcome of death from any cause or hospitalization for heart failure (37.2% vs 38.0%; 95% CI, 0.78-1.28; P = .96). Moreover, the degree of LVEF improvement, assessed by follow-up echocardiogram read by the core lab, showed no difference in the degree of LVEF improvement between groups at 6 and 12 months. Finally, although results of the QOL assessment using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated, patient-reported, heart-failure-specific QOL scale, favored the PCI group at 6 and 12 months of follow-up, the difference had diminished at 24 months.
The main strength of the REVIVED study was that it targeted a patient population with severe coronary artery disease, including left main disease and severely reduced ejection fraction, that historically have been excluded from large-scale randomized controlled studies evaluating PCI with OMT compared to OMT alone.7 However, there are several points to consider when interpreting the results of this study. First, further details of the PCI procedures are necessary. The REVIVED study recommended revascularization of all territories with viable myocardium; the anatomical revascularization index utilizing the British Cardiovascular Intervention Society (BCIS) Jeopardy Score was 71%. It is important to note that this jeopardy score was operator-reported and the core-lab adjudicated anatomical revascularization rate may be lower. Although viability testing primarily utilizing cardiac magnetic resonance imaging was performed in most patients, correlation between the revascularization territory and the viable segments has yet to be reported. Moreover, procedural details such as use of intravascular ultrasound and physiological testing, known to improve clinical outcome, need to be reported.8,9
Second, there is a high prevalence of ischemic cardiomyopathy, and it is important to note that the patients included in this study were highly selected from daily clinical practice, as evidenced by the prolonged enrollment period (8 years). Individuals were largely stable patients with less complex coronary anatomy as evidenced by the median interval from angiography to randomization of 80 days. Taking into consideration the degree of left ventricular dysfunction for patients included in the trial, only 14% of the patients had left main disease and half of the patients only had 2-vessel disease. The severity of the left main disease also needs to be clarified as it is likely that patients the operator determined to be critical were not enrolled in the study. Furthermore, the standard of care based on the STICH trial is to refer patients with severe multivessel coronary artery disease to CABG, making it more likely that patients with more severe and complex disease were not included in this trial. It is also important to note that this study enrolled patients with stable ischemic heart disease, and the data do not apply to patients presenting with acute coronary syndrome.
Third, although the primary outcome was similar between the groups, the secondary outcome of unplanned revascularization was lower in the PCI group. In addition, the rate of acute myocardial infarction (MI) was similar between the 2 groups, but the rate of spontaneous MI was lower in the PCI group compared to the OMT group (5.2% vs 9.3%) as 40% of MI cases in the PCI group were periprocedural MIs. The correlation between periprocedural MI and long-term outcomes has been modest compared to spontaneous MI. Moreover, with the longer follow-up, the number of spontaneous MI cases is expected to rise while the number of periprocedural MI cases is not. Extending the follow-up period is also important, as the STICH extension trial showed a statistically significant difference at 10-year follow up despite negative results at the time of the original publication.
Fourth, the REVIVED trial randomized a significantly lower number of patients compared to the STICH trial, and the authors reported fewer primary-outcome events than the estimated number needed to achieve the power to assess the primary hypothesis. In addition, significant improvements in medical treatment for heart failure with reduced ejection fraction since the STICH trial make comparison of PCI vs CABG in this patient population unfeasible.
Finally, although severe angina was not an exclusion criterion, two-thirds of the patients enrolled had no angina, and only 2% of the patients had baseline severe angina. This is important to consider when interpreting the results of the patient-reported health status as previous studies have shown that patients with worse angina at baseline derive the largest improvement in their QOL,10,11 and symptom improvement is the main indication for PCI in patients with stable ischemic heart disease.
Applications for Clinical Practice and System Implementation
In patients with severe left ventricular systolic dysfunction and multivessel stable ischemic heart disease who are well compensated and have little or no angina at baseline, OMT alone as an initial strategy may be considered against the addition of PCI after careful risk and benefit discussion. Further details about revascularization and extended follow-up data from the REVIVED trial are necessary.
Practice Points
- Patients with ischemic cardiomyopathy with reduced ejection fraction have been an understudied population in previous studies.
- Further studies are necessary to understand the benefits of revascularization and the role of viability testing in this population.
– Taishi Hirai MD, and Ziad Sayed Ahmad, MD
University of Missouri, Columbia, MO
1. Nowbar AN, Gitto M, Howard JP, et al. Mortality from ischemic heart disease. Circ Cardiovasc Qual Outcomes. 2019;12(6):e005375. doi:10.1161/CIRCOUTCOMES
2. Velazquez EJ, Lee KL, Deja MA, et al; for the STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616. doi:10.1056/NEJMoa1100356
3. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med. 2016;374(16):1511-1520. doi:10.1056/NEJMoa1602001
4. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006
5. Kirtane AJ, Doshi D, Leon MB, et al. Treatment of higher-risk patients with an indication for revascularization: evolution within the field of contemporary percutaneous coronary intervention. Circulation. 2016;134(5):422-431. doi:10.1161/CIRCULATIONAHA
6. Perera D, Clayton T, O’Kane PD, et al. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med. 2022;387(15):1351-1360. doi:10.1056/NEJMoa2206606
7. Maron DJ, Hochman JS, Reynolds HR, et al. Initial invasive or conservative strategy for stable coronary disease. Circulation. 2020;142(18):1725-1735. doi:10.1161/CIRCULATIONAHA
8. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991-1001. doi:10.1056/NEJMoa1205361
9. Zhang J, Gao X, Kan J, et al. Intravascular ultrasound versus angiography-guided drug-eluting stent implantation: The ULTIMATE trial. J Am Coll Cardiol. 2018;72(24):3126-3137. doi:10.1016/j.jacc.2018.09.013
10. Spertus JA, Jones PG, Maron DJ, et al. Health-status outcomes with invasive or conservative care in coronary disease. N Engl J Med. 2020;382(15):1408-1419. doi:10.1056/NEJMoa1916370
11. Hirai T, Grantham JA, Sapontis J, et al. Quality of life changes after chronic total occlusion angioplasty in patients with baseline refractory angina. Circ Cardiovasc Interv. 2019;12:e007558. doi:10.1161/CIRCINTERVENTIONS.118.007558
Study 1 Overview (STICHES Investigators)
Objective: To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical therapy (OMT) alone, in patients with coronary artery disease, heart failure, and severe left ventricular dysfunction. Design: Multicenter, randomized, prospective study with extended follow-up (median duration of 9.8 years).
Setting and participants: A total of 1212 patients with left ventricular ejection fraction (LVEF) of 35% or less and coronary artery disease were randomized to medical therapy plus CABG or OMT alone at 127 clinical sites in 26 countries.
Main outcome measures: The primary endpoint was death from any cause. Main secondary endpoints were death from cardiovascular causes and a composite outcome of death from any cause or hospitalization for cardiovascular causes.
Main results: There were 359 primary outcome all-cause deaths (58.9%) in the CABG group and 398 (66.1%) in the medical therapy group (hazard ratio [HR], 0.84; 95% CI, 0.73-0.97; P = .02). Death from cardiovascular causes was reported in 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical therapy group (HR, 0.79; 95% CI, 0.66-0.93; P < .01). The composite outcome of death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and 467 patients (87.0%) in the medical therapy group (HR, 0.72; 95% CI, 0.64-0.82; P < .01).
Conclusion: Over a median follow-up of 9.8 years in patients with ischemic cardiomyopathy with severely reduced ejection fraction, the rates of death from any cause, death from cardiovascular causes, and the composite of death from any cause or hospitalization for cardiovascular causes were significantly lower in patients undergoing CABG than in patients receiving medical therapy alone.
Study 2 Overview (REVIVED BCIS Trial Group)
Objective: To assess whether percutaneous coronary intervention (PCI) can improve survival and left ventricular function in patients with severe left ventricular systolic dysfunction as compared to OMT alone.
Design: Multicenter, randomized, prospective study.
Setting and participants: A total of 700 patients with LVEF <35% with severe coronary artery disease amendable to PCI and demonstrable myocardial viability were randomly assigned to either PCI plus optimal medical therapy (PCI group) or OMT alone (OMT group).
Main outcome measures: The primary outcome was death from any cause or hospitalization for heart failure. The main secondary outcomes were LVEF at 6 and 12 months and quality of life (QOL) scores.
Main results: Over a median follow-up of 41 months, the primary outcome was reported in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the OMT group (HR, 0.99; 95% CI, 0.78-1.27; P = .96). The LVEF was similar in the 2 groups at 6 months (mean difference, –1.6 percentage points; 95% CI, –3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, –1.7 to 3.4). QOL scores at 6 and 12 months favored the PCI group, but the difference had diminished at 24 months.
Conclusion: In patients with severe ischemic cardiomyopathy, revascularization by PCI in addition to OMT did not result in a lower incidence of death from any cause or hospitalization from heart failure.
Commentary
Coronary artery disease is the most common cause of heart failure with reduced ejection fraction and an important cause of mortality.1 Patients with ischemic cardiomyopathy with reduced ejection fraction are often considered for revascularization in addition to OMT and device therapies. Although there have been multiple retrospective studies and registries suggesting that cardiac outcomes and LVEF improve with revascularization, the number of large-scale prospective studies that assessed this clinical question and randomized patients to revascularization plus OMT compared to OMT alone has been limited.
In the Surgical Treatment for Ischemic Heart Failure (STICH) study,2,3 eligible patients had coronary artery disease amendable to CABG and a LVEF of 35% or less. Patients (N = 1212) were randomly assigned to CABG plus OMT or OMT alone between July 2002 and May 2007. The original study, with a median follow-up of 5 years, did not show survival benefit, but the investigators reported that the primary outcome of death from any cause was significantly lower in the CABG group compared to OMT alone when follow-up of the same study population was extended to 9.8 years (58.9% vs 66.1%, P = .02). The findings from this study led to a class I guideline recommendation of CABG over medical therapy in patients with multivessel disease and low ejection fraction.4
Since the STICH trial was designed, there have been significant improvements in devices and techniques used for PCI, and the procedure is now widely performed in patients with multivessel disease.5 The advantages of PCI over CABG include shorter recovery times and lower risk of immediate complications. In this context, the recently reported Revascularization for Ischemic Ventricular Dysfunction (REVIVED) study assessed clinical outcomes in patients with severe coronary artery disease and reduced ejection fraction by randomizing patients to either PCI with OMT or OMT alone.6 At a median follow-up of 3.5 years, the investigators found no difference in the primary outcome of death from any cause or hospitalization for heart failure (37.2% vs 38.0%; 95% CI, 0.78-1.28; P = .96). Moreover, the degree of LVEF improvement, assessed by follow-up echocardiogram read by the core lab, showed no difference in the degree of LVEF improvement between groups at 6 and 12 months. Finally, although results of the QOL assessment using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated, patient-reported, heart-failure-specific QOL scale, favored the PCI group at 6 and 12 months of follow-up, the difference had diminished at 24 months.
The main strength of the REVIVED study was that it targeted a patient population with severe coronary artery disease, including left main disease and severely reduced ejection fraction, that historically have been excluded from large-scale randomized controlled studies evaluating PCI with OMT compared to OMT alone.7 However, there are several points to consider when interpreting the results of this study. First, further details of the PCI procedures are necessary. The REVIVED study recommended revascularization of all territories with viable myocardium; the anatomical revascularization index utilizing the British Cardiovascular Intervention Society (BCIS) Jeopardy Score was 71%. It is important to note that this jeopardy score was operator-reported and the core-lab adjudicated anatomical revascularization rate may be lower. Although viability testing primarily utilizing cardiac magnetic resonance imaging was performed in most patients, correlation between the revascularization territory and the viable segments has yet to be reported. Moreover, procedural details such as use of intravascular ultrasound and physiological testing, known to improve clinical outcome, need to be reported.8,9
Second, there is a high prevalence of ischemic cardiomyopathy, and it is important to note that the patients included in this study were highly selected from daily clinical practice, as evidenced by the prolonged enrollment period (8 years). Individuals were largely stable patients with less complex coronary anatomy as evidenced by the median interval from angiography to randomization of 80 days. Taking into consideration the degree of left ventricular dysfunction for patients included in the trial, only 14% of the patients had left main disease and half of the patients only had 2-vessel disease. The severity of the left main disease also needs to be clarified as it is likely that patients the operator determined to be critical were not enrolled in the study. Furthermore, the standard of care based on the STICH trial is to refer patients with severe multivessel coronary artery disease to CABG, making it more likely that patients with more severe and complex disease were not included in this trial. It is also important to note that this study enrolled patients with stable ischemic heart disease, and the data do not apply to patients presenting with acute coronary syndrome.
Third, although the primary outcome was similar between the groups, the secondary outcome of unplanned revascularization was lower in the PCI group. In addition, the rate of acute myocardial infarction (MI) was similar between the 2 groups, but the rate of spontaneous MI was lower in the PCI group compared to the OMT group (5.2% vs 9.3%) as 40% of MI cases in the PCI group were periprocedural MIs. The correlation between periprocedural MI and long-term outcomes has been modest compared to spontaneous MI. Moreover, with the longer follow-up, the number of spontaneous MI cases is expected to rise while the number of periprocedural MI cases is not. Extending the follow-up period is also important, as the STICH extension trial showed a statistically significant difference at 10-year follow up despite negative results at the time of the original publication.
Fourth, the REVIVED trial randomized a significantly lower number of patients compared to the STICH trial, and the authors reported fewer primary-outcome events than the estimated number needed to achieve the power to assess the primary hypothesis. In addition, significant improvements in medical treatment for heart failure with reduced ejection fraction since the STICH trial make comparison of PCI vs CABG in this patient population unfeasible.
Finally, although severe angina was not an exclusion criterion, two-thirds of the patients enrolled had no angina, and only 2% of the patients had baseline severe angina. This is important to consider when interpreting the results of the patient-reported health status as previous studies have shown that patients with worse angina at baseline derive the largest improvement in their QOL,10,11 and symptom improvement is the main indication for PCI in patients with stable ischemic heart disease.
Applications for Clinical Practice and System Implementation
In patients with severe left ventricular systolic dysfunction and multivessel stable ischemic heart disease who are well compensated and have little or no angina at baseline, OMT alone as an initial strategy may be considered against the addition of PCI after careful risk and benefit discussion. Further details about revascularization and extended follow-up data from the REVIVED trial are necessary.
Practice Points
- Patients with ischemic cardiomyopathy with reduced ejection fraction have been an understudied population in previous studies.
- Further studies are necessary to understand the benefits of revascularization and the role of viability testing in this population.
– Taishi Hirai MD, and Ziad Sayed Ahmad, MD
University of Missouri, Columbia, MO
Study 1 Overview (STICHES Investigators)
Objective: To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical therapy (OMT) alone, in patients with coronary artery disease, heart failure, and severe left ventricular dysfunction. Design: Multicenter, randomized, prospective study with extended follow-up (median duration of 9.8 years).
Setting and participants: A total of 1212 patients with left ventricular ejection fraction (LVEF) of 35% or less and coronary artery disease were randomized to medical therapy plus CABG or OMT alone at 127 clinical sites in 26 countries.
Main outcome measures: The primary endpoint was death from any cause. Main secondary endpoints were death from cardiovascular causes and a composite outcome of death from any cause or hospitalization for cardiovascular causes.
Main results: There were 359 primary outcome all-cause deaths (58.9%) in the CABG group and 398 (66.1%) in the medical therapy group (hazard ratio [HR], 0.84; 95% CI, 0.73-0.97; P = .02). Death from cardiovascular causes was reported in 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical therapy group (HR, 0.79; 95% CI, 0.66-0.93; P < .01). The composite outcome of death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and 467 patients (87.0%) in the medical therapy group (HR, 0.72; 95% CI, 0.64-0.82; P < .01).
Conclusion: Over a median follow-up of 9.8 years in patients with ischemic cardiomyopathy with severely reduced ejection fraction, the rates of death from any cause, death from cardiovascular causes, and the composite of death from any cause or hospitalization for cardiovascular causes were significantly lower in patients undergoing CABG than in patients receiving medical therapy alone.
Study 2 Overview (REVIVED BCIS Trial Group)
Objective: To assess whether percutaneous coronary intervention (PCI) can improve survival and left ventricular function in patients with severe left ventricular systolic dysfunction as compared to OMT alone.
Design: Multicenter, randomized, prospective study.
Setting and participants: A total of 700 patients with LVEF <35% with severe coronary artery disease amendable to PCI and demonstrable myocardial viability were randomly assigned to either PCI plus optimal medical therapy (PCI group) or OMT alone (OMT group).
Main outcome measures: The primary outcome was death from any cause or hospitalization for heart failure. The main secondary outcomes were LVEF at 6 and 12 months and quality of life (QOL) scores.
Main results: Over a median follow-up of 41 months, the primary outcome was reported in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the OMT group (HR, 0.99; 95% CI, 0.78-1.27; P = .96). The LVEF was similar in the 2 groups at 6 months (mean difference, –1.6 percentage points; 95% CI, –3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, –1.7 to 3.4). QOL scores at 6 and 12 months favored the PCI group, but the difference had diminished at 24 months.
Conclusion: In patients with severe ischemic cardiomyopathy, revascularization by PCI in addition to OMT did not result in a lower incidence of death from any cause or hospitalization from heart failure.
Commentary
Coronary artery disease is the most common cause of heart failure with reduced ejection fraction and an important cause of mortality.1 Patients with ischemic cardiomyopathy with reduced ejection fraction are often considered for revascularization in addition to OMT and device therapies. Although there have been multiple retrospective studies and registries suggesting that cardiac outcomes and LVEF improve with revascularization, the number of large-scale prospective studies that assessed this clinical question and randomized patients to revascularization plus OMT compared to OMT alone has been limited.
In the Surgical Treatment for Ischemic Heart Failure (STICH) study,2,3 eligible patients had coronary artery disease amendable to CABG and a LVEF of 35% or less. Patients (N = 1212) were randomly assigned to CABG plus OMT or OMT alone between July 2002 and May 2007. The original study, with a median follow-up of 5 years, did not show survival benefit, but the investigators reported that the primary outcome of death from any cause was significantly lower in the CABG group compared to OMT alone when follow-up of the same study population was extended to 9.8 years (58.9% vs 66.1%, P = .02). The findings from this study led to a class I guideline recommendation of CABG over medical therapy in patients with multivessel disease and low ejection fraction.4
Since the STICH trial was designed, there have been significant improvements in devices and techniques used for PCI, and the procedure is now widely performed in patients with multivessel disease.5 The advantages of PCI over CABG include shorter recovery times and lower risk of immediate complications. In this context, the recently reported Revascularization for Ischemic Ventricular Dysfunction (REVIVED) study assessed clinical outcomes in patients with severe coronary artery disease and reduced ejection fraction by randomizing patients to either PCI with OMT or OMT alone.6 At a median follow-up of 3.5 years, the investigators found no difference in the primary outcome of death from any cause or hospitalization for heart failure (37.2% vs 38.0%; 95% CI, 0.78-1.28; P = .96). Moreover, the degree of LVEF improvement, assessed by follow-up echocardiogram read by the core lab, showed no difference in the degree of LVEF improvement between groups at 6 and 12 months. Finally, although results of the QOL assessment using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated, patient-reported, heart-failure-specific QOL scale, favored the PCI group at 6 and 12 months of follow-up, the difference had diminished at 24 months.
The main strength of the REVIVED study was that it targeted a patient population with severe coronary artery disease, including left main disease and severely reduced ejection fraction, that historically have been excluded from large-scale randomized controlled studies evaluating PCI with OMT compared to OMT alone.7 However, there are several points to consider when interpreting the results of this study. First, further details of the PCI procedures are necessary. The REVIVED study recommended revascularization of all territories with viable myocardium; the anatomical revascularization index utilizing the British Cardiovascular Intervention Society (BCIS) Jeopardy Score was 71%. It is important to note that this jeopardy score was operator-reported and the core-lab adjudicated anatomical revascularization rate may be lower. Although viability testing primarily utilizing cardiac magnetic resonance imaging was performed in most patients, correlation between the revascularization territory and the viable segments has yet to be reported. Moreover, procedural details such as use of intravascular ultrasound and physiological testing, known to improve clinical outcome, need to be reported.8,9
Second, there is a high prevalence of ischemic cardiomyopathy, and it is important to note that the patients included in this study were highly selected from daily clinical practice, as evidenced by the prolonged enrollment period (8 years). Individuals were largely stable patients with less complex coronary anatomy as evidenced by the median interval from angiography to randomization of 80 days. Taking into consideration the degree of left ventricular dysfunction for patients included in the trial, only 14% of the patients had left main disease and half of the patients only had 2-vessel disease. The severity of the left main disease also needs to be clarified as it is likely that patients the operator determined to be critical were not enrolled in the study. Furthermore, the standard of care based on the STICH trial is to refer patients with severe multivessel coronary artery disease to CABG, making it more likely that patients with more severe and complex disease were not included in this trial. It is also important to note that this study enrolled patients with stable ischemic heart disease, and the data do not apply to patients presenting with acute coronary syndrome.
Third, although the primary outcome was similar between the groups, the secondary outcome of unplanned revascularization was lower in the PCI group. In addition, the rate of acute myocardial infarction (MI) was similar between the 2 groups, but the rate of spontaneous MI was lower in the PCI group compared to the OMT group (5.2% vs 9.3%) as 40% of MI cases in the PCI group were periprocedural MIs. The correlation between periprocedural MI and long-term outcomes has been modest compared to spontaneous MI. Moreover, with the longer follow-up, the number of spontaneous MI cases is expected to rise while the number of periprocedural MI cases is not. Extending the follow-up period is also important, as the STICH extension trial showed a statistically significant difference at 10-year follow up despite negative results at the time of the original publication.
Fourth, the REVIVED trial randomized a significantly lower number of patients compared to the STICH trial, and the authors reported fewer primary-outcome events than the estimated number needed to achieve the power to assess the primary hypothesis. In addition, significant improvements in medical treatment for heart failure with reduced ejection fraction since the STICH trial make comparison of PCI vs CABG in this patient population unfeasible.
Finally, although severe angina was not an exclusion criterion, two-thirds of the patients enrolled had no angina, and only 2% of the patients had baseline severe angina. This is important to consider when interpreting the results of the patient-reported health status as previous studies have shown that patients with worse angina at baseline derive the largest improvement in their QOL,10,11 and symptom improvement is the main indication for PCI in patients with stable ischemic heart disease.
Applications for Clinical Practice and System Implementation
In patients with severe left ventricular systolic dysfunction and multivessel stable ischemic heart disease who are well compensated and have little or no angina at baseline, OMT alone as an initial strategy may be considered against the addition of PCI after careful risk and benefit discussion. Further details about revascularization and extended follow-up data from the REVIVED trial are necessary.
Practice Points
- Patients with ischemic cardiomyopathy with reduced ejection fraction have been an understudied population in previous studies.
- Further studies are necessary to understand the benefits of revascularization and the role of viability testing in this population.
– Taishi Hirai MD, and Ziad Sayed Ahmad, MD
University of Missouri, Columbia, MO
1. Nowbar AN, Gitto M, Howard JP, et al. Mortality from ischemic heart disease. Circ Cardiovasc Qual Outcomes. 2019;12(6):e005375. doi:10.1161/CIRCOUTCOMES
2. Velazquez EJ, Lee KL, Deja MA, et al; for the STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616. doi:10.1056/NEJMoa1100356
3. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med. 2016;374(16):1511-1520. doi:10.1056/NEJMoa1602001
4. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006
5. Kirtane AJ, Doshi D, Leon MB, et al. Treatment of higher-risk patients with an indication for revascularization: evolution within the field of contemporary percutaneous coronary intervention. Circulation. 2016;134(5):422-431. doi:10.1161/CIRCULATIONAHA
6. Perera D, Clayton T, O’Kane PD, et al. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med. 2022;387(15):1351-1360. doi:10.1056/NEJMoa2206606
7. Maron DJ, Hochman JS, Reynolds HR, et al. Initial invasive or conservative strategy for stable coronary disease. Circulation. 2020;142(18):1725-1735. doi:10.1161/CIRCULATIONAHA
8. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991-1001. doi:10.1056/NEJMoa1205361
9. Zhang J, Gao X, Kan J, et al. Intravascular ultrasound versus angiography-guided drug-eluting stent implantation: The ULTIMATE trial. J Am Coll Cardiol. 2018;72(24):3126-3137. doi:10.1016/j.jacc.2018.09.013
10. Spertus JA, Jones PG, Maron DJ, et al. Health-status outcomes with invasive or conservative care in coronary disease. N Engl J Med. 2020;382(15):1408-1419. doi:10.1056/NEJMoa1916370
11. Hirai T, Grantham JA, Sapontis J, et al. Quality of life changes after chronic total occlusion angioplasty in patients with baseline refractory angina. Circ Cardiovasc Interv. 2019;12:e007558. doi:10.1161/CIRCINTERVENTIONS.118.007558
1. Nowbar AN, Gitto M, Howard JP, et al. Mortality from ischemic heart disease. Circ Cardiovasc Qual Outcomes. 2019;12(6):e005375. doi:10.1161/CIRCOUTCOMES
2. Velazquez EJ, Lee KL, Deja MA, et al; for the STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-1616. doi:10.1056/NEJMoa1100356
3. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med. 2016;374(16):1511-1520. doi:10.1056/NEJMoa1602001
4. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006
5. Kirtane AJ, Doshi D, Leon MB, et al. Treatment of higher-risk patients with an indication for revascularization: evolution within the field of contemporary percutaneous coronary intervention. Circulation. 2016;134(5):422-431. doi:10.1161/CIRCULATIONAHA
6. Perera D, Clayton T, O’Kane PD, et al. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med. 2022;387(15):1351-1360. doi:10.1056/NEJMoa2206606
7. Maron DJ, Hochman JS, Reynolds HR, et al. Initial invasive or conservative strategy for stable coronary disease. Circulation. 2020;142(18):1725-1735. doi:10.1161/CIRCULATIONAHA
8. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991-1001. doi:10.1056/NEJMoa1205361
9. Zhang J, Gao X, Kan J, et al. Intravascular ultrasound versus angiography-guided drug-eluting stent implantation: The ULTIMATE trial. J Am Coll Cardiol. 2018;72(24):3126-3137. doi:10.1016/j.jacc.2018.09.013
10. Spertus JA, Jones PG, Maron DJ, et al. Health-status outcomes with invasive or conservative care in coronary disease. N Engl J Med. 2020;382(15):1408-1419. doi:10.1056/NEJMoa1916370
11. Hirai T, Grantham JA, Sapontis J, et al. Quality of life changes after chronic total occlusion angioplasty in patients with baseline refractory angina. Circ Cardiovasc Interv. 2019;12:e007558. doi:10.1161/CIRCINTERVENTIONS.118.007558
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>1122 JCOM ORR Hirai</fileName> <TBEID>0C02B654.SIG</TBEID> <TBUniqueIdentifier>NJ_0C02B654</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname>The Role of Revascularization an</storyname> <articleType>1</articleType> <TBLocation>Copyfitting-JCOM</TBLocation> <QCDate/> <firstPublished>20221117T160002</firstPublished> <LastPublished>20221117T160003</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20221117T160002</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline/> <bylineText/> <bylineFull/> <bylineTitleText>Velazquez E, Lee KL, Jones RH, et al; STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med. 2016;374(16):1511-1520. doi:10.1056/NEJMoa1602001Perera D, Clayton T, O’Kane P, et al; REVIVED-BCIS Investigators. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med. 2022;387(15):1351-1360. doi:10.1056/NEJMoa2206606</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>Objective: To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical the</metaDescription> <articlePDF/> <teaserImage/> <title>The Role of Revascularization and Viability Testing in Patients With Multivessel Coronary Artery Disease and Severely Reduced Ejection Fraction</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi>10.12788/jcom.0117</doi> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>jcom</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">40713</term> </publications> <sections> <term canonical="true">41021</term> </sections> <topics> <term canonical="true">194</term> <term>325</term> <term>38029</term> <term>230</term> <term>312</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>The Role of Revascularization and Viability Testing in Patients With Multivessel Coronary Artery Disease and Severely Reduced Ejection Fraction</title> <deck/> </itemMeta> <itemContent> <p class="sub1">Study 1 Overview (STICHES Investigators) </p> <p><strong><em>O</em></strong><strong><em>bjective:</em></strong> To assess the survival benefit of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, compared to optimal medical therapy (OMT) alone, in patients with coronary artery disease, heart failure, and severe left ventricular dysfunction. <strong><em>Design:</em></strong> Multicenter, randomized, prospective study with extended follow-up (median duration of 9.8 years). <br/><br/><strong><em>Setting and participants:</em></strong> A total of 1212 patients with left ventricular ejection fraction (LVEF) of 35% or less and coronary artery disease were randomized to medical therapy plus CABG or OMT alone at 127 clinical sites in 26 countries. <br/><br/><strong><em>Main outcome measures:</em></strong> The primary endpoint was death from any cause. Main secondary endpoints were death from cardiovascular causes and a composite outcome of death from any cause or hospitalization for cardiovascular causes. <br/><br/><strong><em>Main results:</em></strong> There were 359 primary outcome all-cause deaths (58.9%) in the CABG group and 398 (66.1%) in the medical therapy group (hazard ratio [HR], 0.84; 95% CI, 0.73-0.97; <em>P </em>= .02). Death from cardiovascular causes was reported in 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical therapy group (HR, 0.79; 95% CI, 0.66-0.93; <em>P</em> < .01). The composite outcome of death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and 467 patients (87.0%) in the medical therapy group (HR, 0.72; 95% CI, 0.64-0.82; <em>P</em> < .01). <br/><br/><strong><em>Conclusion:</em></strong> Over a median follow-up of 9.8 years in patients with ischemic cardiomyopathy with severely reduced ejection fraction, the rates of death from any cause, death from cardiovascular causes, and the composite of death from any cause or hospitalization for cardiovascular causes were significantly lower in patients undergoing CABG than in patients receiving medical therapy alone. </p> <p class="sub1">Study 2 Overview (REVIVED BCIS Trial Group)</p> <p><strong><em>Objective:</em></strong> To assess whether percutaneous coronary intervention (PCI) can improve survival and left ventricular function in patients with severe left ventricular systolic dysfunction as compared to OMT alone. <br/><br/><strong><em>Design:</em></strong> Multicenter, randomized, prospective study. <br/><br/><strong><em>Setting and participants:</em></strong> A total of 700 patients with LVEF <35% with severe coronary artery disease amendable to PCI and demonstrable myocardial viability were randomly assigned to either PCI plus optimal medical therapy (PCI group) or OMT alone (OMT group). <br/><br/><strong><em>Main outcome measures:</em></strong> The primary outcome was death from any cause or hospitalization for heart failure. The main secondary outcomes were LVEF at 6 and 12 months and quality of life (QOL) scores. <br/><br/><strong><em>Main results:</em></strong> Over a median follow-up of 41 months, the primary outcome was reported in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the OMT group (HR, 0.99; 95% CI, 0.78-1.27; <em>P </em>= .96). The LVEF was similar in the 2 groups at 6 months (mean difference, –1.6 percentage points; 95% CI, –3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, –1.7 to 3.4). QOL scores at 6 and 12 months favored the PCI group, but the difference had diminished at 24 months. <br/><br/><strong><em>Conclusion:</em></strong> In patients with severe ischemic cardiomyopathy, revascularization by PCI in addition to OMT did not result in a lower incidence of death from any cause or hospitalization from heart failure. </p> <p class="sub1">Commentary</p> <p>Coronary artery disease is the most common cause of heart failure with reduced ejection fraction and an important cause of mortality.<sup>1</sup> Patients with ischemic cardiomyopathy with reduced ejection fraction are often considered for revascularization in addition to OMT and device therapies. Although there have been multiple retrospective studies and registries suggesting that cardiac outcomes and LVEF improve with revascularization, the number of large-scale prospective studies that assessed this clinical question and randomized patients to revascularization plus OMT compared to OMT alone has been limited. </p> <p>In the Surgical Treatment for Ischemic Heart Failure (STICH) study,<sup>2,3</sup> eligible patients had coronary artery disease amendable to CABG and a LVEF of 35% or less. Patients (N = 1212) were randomly assigned to CABG plus OMT or OMT alone between July 2002 and May 2007. The original study, with a median follow-up of 5 years, did not show survival benefit, but the investigators reported that the primary outcome of death from any cause was significantly lower in the CABG group compared to OMT alone when follow-up of the same study population was extended to 9.8 years (58.9% vs 66.1%, <em>P </em>= .02). The findings from this study led to a class I guideline recommendation of CABG over medical therapy in patients with multivessel disease and low ejection fraction.<sup>4</sup> <br/><br/>Since the STICH trial was designed, there have been significant improvements in devices and techniques used for PCI, and the procedure is now widely performed in patients with multivessel disease.<sup>5</sup> The advantages of PCI over CABG include shorter recovery times and lower risk of immediate complications. In this context, the recently reported Revascularization for Ischemic Ventricular Dysfunction (REVIVED) study assessed clinical outcomes in patients with severe coronary artery disease and reduced ejection fraction by randomizing patients to either PCI with OMT or OMT alone.<sup>6</sup> At a median follow-up of 3.5 years, the investigators found no difference in the primary outcome of death from any cause or hospitalization for heart failure (37.2% vs 38.0%; 95% CI, 0.78-1.28; <em>P </em>= .96). Moreover, the degree of LVEF improvement, assessed by follow-up echocardiogram read by the core lab, showed no difference in the degree of LVEF improvement between groups at 6 and 12 months. Finally, although results of the QOL assessment using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated, patient-reported, heart-failure-specific QOL scale, favored the PCI group at 6 and 12 months of follow-up, the difference had diminished at 24 months. <br/><br/>The main strength of the REVIVED study was that it targeted a patient population with severe coronary artery disease, including left main disease and severely reduced ejection fraction, that historically have been excluded from large-scale randomized controlled studies evaluating PCI with OMT compared to OMT alone.<sup>7</sup> However, there are several points to consider when interpreting the results of this study. First, further details of the PCI procedures are necessary. The REVIVED study recommended revascularization of all territories with viable myocardium; the anatomical revascularization index utilizing the British Cardiovascular Intervention Society (BCIS) Jeopardy Score was 71%. It is important to note that this jeopardy score was operator-reported and the core-lab adjudicated anatomical revascularization rate may be lower. Although viability testing primarily utilizing cardiac magnetic resonance imaging was performed in most patients, correlation between the revascularization territory and the viable segments has yet to be reported. Moreover, procedural details such as use of intravascular ultrasound and physiological testing, known to improve clinical outcome, need to be reported.<sup>8,9</sup> <br/><br/>Second, there is a high prevalence of ischemic cardiomyopathy, and it is important to note that the patients included in this study were highly selected from daily clinical practice, as evidenced by the prolonged enrollment period (8 years). Individuals were largely stable patients with less complex coronary anatomy as evidenced by the median interval from angiography to randomization of 80 days. Taking into consideration the degree of left ventricular dysfunction for patients included in the trial, only 14% of the patients had left main disease and half of the patients only had 2-vessel disease. The severity of the left main disease also needs to be clarified as it is likely that patients the operator determined to be critical were not enrolled in the study. Furthermore, the standard of care based on the STICH trial is to refer patients with severe multivessel coronary artery disease to CABG, making it more likely that patients with more severe and complex disease were not included in this trial. It is also important to note that this study enrolled patients with stable ischemic heart disease, and the data do not apply to patients presenting with acute coronary syndrome. <br/><br/>Third, although the primary outcome was similar between the groups, the secondary outcome of unplanned revascularization was lower in the PCI group. In addition, the rate of acute myocardial infarction (MI) was similar between the 2 groups, but the rate of spontaneous MI was lower in the PCI group compared to the OMT group (5.2% vs 9.3%) as 40% of MI cases in the PCI group were periprocedural MIs. The correlation between periprocedural MI and long-term outcomes has been modest compared to spontaneous MI. Moreover, with the longer follow-up, the number of spontaneous MI cases is expected to rise while the number of periprocedural MI cases is not. Extending the follow-up period is also important, as the STICH extension trial showed a statistically significant difference at 10-year follow up despite negative results at the time of the original publication. <br/><br/>Fourth, the REVIVED trial randomized a significantly lower number of patients compared to the STICH trial, and the authors reported fewer primary-outcome events than the estimated number needed to achieve the power to assess the primary hypothesis. In addition, significant improvements in medical treatment for heart failure with reduced ejection fraction since the STICH trial make comparison of PCI vs CABG in this patient population unfeasible. <br/><br/>Finally, although severe angina was not an exclusion criterion, two-thirds of the patients enrolled had no angina, and only 2% of the patients had baseline severe angina. This is important to consider when interpreting the results of the patient-reported health status as previous studies have shown that patients with worse angina at baseline derive the largest improvement in their QOL,<sup>10,11</sup> and symptom improvement is the main indication for PCI in patients with stable ischemic heart disease. </p> <p class="sub1">Applications for Clinical Practice and System Implementation</p> <p>In patients with severe left ventricular systolic dysfunction and multivessel stable ischemic heart disease who are well compensated and have little or no angina at baseline, OMT alone as an initial strategy may be considered against the addition of PCI after careful risk and benefit discussion. Further details about revascularization and extended follow-up data from the REVIVED trial are necessary. </p> <p class="sub1">Practice Points</p> <ul class="body"> <li>Patients with ischemic cardiomyopathy with reduced ejection fraction have been an understudied population in previous studies. </li> <li>Further studies are necessary to understand the benefits of revascularization and the role of viability testing in this population. </li> </ul> <p> <em>–</em> <em>Taishi Hirai MD, and Ziad Sayed Ahmad, MD<br/><br/>University of Missouri, Columbia, MO<br/><br/>doi:10.12788/jcom.0117</em> </p> <p class="sub1">References</p> <p class="reference">1. Nowbar AN, Gitto M, Howard JP, et al. Mortality from ischemic heart disease. <em>Circ Cardiovasc Qual Outcomes</em>. 2019;12(6):e005375. doi:10.1161/CIRCOUTCOMES</p> <p class="reference">2. Velazquez EJ, Lee KL, Deja MA, et al; for the STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. <em>N Engl J Med. </em>2011;364(17):1607-1616. doi:10.1056/NEJMoa1100356<br/><br/>3. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. <em>N Engl J Med.</em> 2016;374(16):1511-1520. doi:10.1056/NEJMoa1602001<br/><br/>4. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. <em>J Am Coll Cardiol.</em> 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006<br/><br/>5. Kirtane AJ, Doshi D, Leon MB, et al. Treatment of higher-risk patients with an indication for revascularization: evolution within the field of contemporary percutaneous coronary intervention. <em>Circulation.</em> 2016;134(5):422-431. doi:10.1161/CIRCULATIONAHA<br/><br/>6. Perera D, Clayton T, O’Kane PD, et al. Percutaneous revascularization for ischemic left ventricular dysfunction. <em>N Engl J Med.</em> 2022;387(15):1351-1360. doi:10.1056/NEJMoa2206606<br/><br/>7. Maron DJ, Hochman JS, Reynolds HR, et al. Initial invasive or conservative strategy for stable coronary disease. <em>Circulation.</em> 2020;142(18):1725-1735. doi:10.1161/CIRCULATIONAHA<br/><br/>8. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. <em>N Engl J Med.</em> 2012;367(11):991-1001. doi:10.1056/NEJMoa1205361<br/><br/>9. Zhang J, Gao X, Kan J, et al. Intravascular ultrasound versus angiography-guided drug-eluting stent implantation: The ULTIMATE trial. <em>J Am Coll Cardiol. </em>2018;72(24):3126-3137. doi:10.1016/j.jacc.2018.09.013<br/><br/>10. Spertus JA, Jones PG, Maron DJ, et al. Health-status outcomes with invasive or conservative care in coronary disease. <em>N Engl J Med.</em> 2020;382(15):1408-1419. doi:10.1056/NEJMoa1916370<br/><br/>11. Hirai T, Grantham JA, Sapontis J, et al. Quality of life changes after chronic total occlusion angioplasty in patients with baseline refractory angina. <em>Circ Cardiovasc Interv. </em>2019;12:e007558. doi:10.1161/CIRCINTERVENTIONS.118.007558</p> </itemContent> </newsItem> </itemSet></root>