Previous studies on exercise tolerance screening in asymptomatic individuals before starting physical activity were not cost-effective due to low specificity. However, given progress in diagnosing and treating coronary artery disease (CAD), a reevaluation of this approach is justified. We aimed to examine whether stress echocardiography (SE) would be cost-effective.

The study was conducted on asymptomatic individuals with no known coronary disease. The decision tree had two arms: in one arm, the subjects underwent stress echocardiography (SE) as a screening test before starting physical activity, and in the other, they did not. The probabilities and utilities of variables in the decision tree were taken from medical literature, and the costs of treatments were obtained from the Israeli Ministry of Health Tarif (HealthCare in Israel is universal, participation in one of four official health insurance organizations is compulsory, and "supplementary insurance" is optional). A 5-year Markov model and Monte Carlo simulation with 1000 iterations were used to assess cost-effectiveness from the insurer's perspective. The variables that had the most significant impact on cost-effectiveness were the prior risk of coronary disease and the frequency of physical activity in the population under study. When cost-effectiveness assessment of SE was conducted in subjects receiving optimal medical therapy (OMT) and revascularization either transcutaneously or with bypass surgery, both groups had almost identical benefits, with a slight advantage for those who did not undergo SE. However, the cost was higher for subjects who underwent SE, and the Incremental Cost-Effectiveness Ratio (ICER) favored the No-SE group. On the other hand, when subjects only received OMT without therapeutic catheterization or bypass surgery, a cost-effectiveness assessment of SE demonstrated a lower cost and higher benefit in the group that underwent SE. In fact, SE was found to be absolutely dominant, with a negative ICER of $(-)27,644, which means that performing SE not only adds effectiveness but also saves expenses. Finally, a cost-effectiveness evaluation was conducted to compare the benefits of performing exercise tolerance testing (ETT) without stress echocardiography in subjects receiving OMT without therapeutic catheterization or bypass surgery. The results showed that the group that underwent ETT had a slightly higher benefit at a higher cost, with an ICER of $1804. This value is much lower than a WTP (willingness-to-pay) of $50,000 per year.

Performing SE as a screening test before starting physical activity in asymptomatic individuals is not cost-effective when the therapeutic options include revascularization. However, when the therapeutic policy is medical therapy without revascularization - as recommended in current guidelines - performing SE screening tests improves subjects' utility and results in financial savings. Carrying out ETT also results in improved utility that is inferior to SE as a screening test. At the same time, the ICER for ETT is still much smaller than the WTP, so performing ETT is worthwhile in cases where SE is unavailable.

Recently, the FFR-Guidance for Complete Nonculprit Revascularization (FULL REVASC) trial in ST elevation myocardial infarction (STEMI) patients with multiple vessel disease (MVD) did not show differences in the composite endpoint of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only percutaneous coronary intervention (PCI) at 4.8 years, although complete revascularization is a recommendation IA in current guidelines. We want to determine through an updated meta-analysis whether complete revascularization is associated with decreased mortality and hard clinical endpoints compared to culprit lesion only PCI.

We searched MEDLINE, Embase, ISI Web of Science, and Cochrane Central Register of Controlled Trials) from January 1990 to April 2024 using the terms "percutaneous coronary intervention" combined with "non culprit lesions" or "culprit lesion" or "complete revascularization" or "incomplete revascularization." Additionally, a "snowball search" was conducted. Only randomized clinical trials (RCT) reporting mortality, re-infarction or new revascularization after at least 12 months and using predominantly drug eluting stents were included. The summary effect of different revascularization strategies on cardiovascular endpoints was estimated and measures of effect size were expressed as odds ratios (ORs).

Eight RCT involving 9515 patients were included, with a follow-up range between 12 months and 4.8 years. Main findings show that culprit lesion revascularization was associated with an increased risk of MI (OR: 1.38; 95% CI: 1.05 to 1.81, I2 42%) and ischemia-guided revascularization (OR: 2.81; 95% CI: 1.86 to 4.26, I2 80%) compared to complete revascularization, without differences in overall mortality (OR: 1.15; 95% CI: 0.98 to 1.36, I2 2%).

In patients with STEMI and MVD without cardiogenic shock, our metanalysis showed that complete revascularization with PCI significantly reduced the risk of non-fatal myocardial reinfarction and ischemic-driven revascularization compared to culprit vessel-only revascularization, without differences in overall mortality.

In patients with stable ischemic heart disease, there is no evidence for the effect of revascularization treatment timing on the need for repeat procedures. We aimed to determine if repeat revascularizations differed among patients who received coronary artery bypass graft surgery after the time recommended by physicians compared with those who had timely percutaneous coronary intervention.

We identified 25,520 British Columbia residents 60 years or older who underwent first-time nonemergency revascularization for angiographically proven, stable left main or multivessel ischemic heart disease between January 1, 2001, and December 31, 2016. We estimated unadjusted and adjusted cumulative incidence functions for repeat revascularization, in the presence of death as a competing risk, after index revascularization or last staged percutaneous coronary intervention for patients undergoing delayed coronary artery bypass grafting compared with timely percutaneous coronary intervention.

After adjustment with inverse probability of treatment weights, at 3 years, patients who underwent delayed coronary artery bypass grafting had a statistically significant lower cumulative incidence of a repeat revascularization compared with patients who received timely percutaneous coronary intervention (4.84% delayed coronary artery bypass grafting, 12.32% timely percutaneous coronary intervention; subdistribution hazard ratio, 0.16, 95% CI, 0.04-0.65).

Patients who undergo delayed coronary artery bypass grafting have a lower cumulative incidence of repeat revascularization than patients who undergo timely percutaneous coronary intervention. Patients who want to wait to receive coronary artery bypass grafting will see the benefit of lower repeat revascularization over percutaneous coronary intervention unaffected by a delay in treatment.

Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for atherosclerosis development. Circular RNA (circRNA) is a specific non-coding RNA that is produced as a closed-loop structure in mammals, and its specific expression pattern is closely related to its cell type and tissue. To clarify the roles of circTLK1 in VSMC phenotypic switching, we performed qRT-PCR, immunoblotting, and immunostaining. qRT-PCR revealed that circTLK1 was upregulated in both mouse models of atherosclerosis in vivo and PDGF (platelet-derived growth factor)-BB-induced VSMCs in vitro. Furthermore, the overexpression of circTLK1 promoted PDGF-BB-induced VSMC phenotypic switching. Conversely, experiments performed in vivo demonstrate that the knockdown of SMC-specific circTLK1 led to a reduction in the development of atherosclerosis. The relationship between circTLK1 and miR-513a-3p and Krüppel-like factor 4 (KLF4) was detected by RNA immunoprecipitation (RIP), luciferase reporter assay, RNA pull-down, and RNA fluorescence in situ hybridization (RNA FISH). Mechanistically, circTLK1 acted as a sponge for miR-513a-3p, leading to the upregulation of KLF4, a key transcription factor for phenotypic switching. Targeting the circTLK1/miR-513a-3p/KLF4 axis may provide a potential therapeutic strategy for atherosclerosis.

Interpretation of recent alterations to the guideline priority of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multivessel disease contests historical data and practice. To reevaluate contemporary outcomes, a large contemporary analysis was conducted comparing CABG with multivessel PCI among Medicare beneficiaries.

The United States Centers for Medicare and Medicaid Services database was evaluated all beneficiaries with acute coronary syndrome undergoing isolated CABG or multivessel PCI (2018-2020). Risk adjustment was performed using multilevel regression analysis, Cox proportional hazards time to event models, and inverse probability of treatment weighting propensity scores.

A total of 104,127 beneficiaries were identified undergoing CABG (n = 51,389) or multivessel PCI (n = 52,738). Before risk adjustment, compared with PCI, CABG patients were associated with younger age (72.9 vs 75.2 years, P < .001), higher Elixhauser Comorbidity Index (5.0 vs 4.2, P < .001), more diabetes (48.5% vs 42.2%, P < .001), higher cost ($54,154 vs $33,484, P < .001), and longer length of stay (11.9 vs 5.8 days, P < .001). After inverse probability of treatment weighting propensity score adjustment, compared with PCI, CABG was associated with lower hospital mortality (odds ratio, 0.74; P < .001), fewer hospital readmissions at 3 years (odds ratio, 0.85; P < .001), fewer coronary reinterventions (hazard ratio, 0.37; P < .001), and improved 3-year survival (hazard ratio, 0.51; P < .001).

Contemporary real-world data from Medicare patients with multivessel disease reveal that CABG outcomes were superior to PCI, providing important longitudinal data to guide patient care and policy development.

The ISCHEMIA trial is a landmark study that has been the subject of heated debate within the cardiovascular community. In this analysis of the ISCHEMIA trial, we aim to set the record straight on the benefits of coronary artery bypass grafting (CABG) and the misinterpretation of this landmark trial. We sought to clarify and reorient this misinterpretation.

We herein analyse the ISCHEMIA trial in detail and describe how its misinterpretation has led to an erroneous guideline recommendation downgrading for prognosis-altering surgical therapy in these at-risk patients.

The interim ISCHEMIA trial findings align with previous evidence where CABG reduces the long-term risks of myocardial infarction and mortality in advanced coronary artery disease. The trial outcomes of a significantly lower rate of cardiovascular mortality and a higher rate of non-cardiovascular mortality with the invasive strategy are explained according to landmark evidence.

The ISCHEMIA trial findings are aligned with previous evidence and should not be used to downgrade recommendations in recent guidelines for the indisputable benefits of CABG.

Composite endpoints are pivotal when assessing rare outcomes over relatively short follow-ups. Most randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with stent implantation to optimal medical therapy (OMT) in chronic coronary syndromes (CCS) patients included both hard and soft outcomes in their primary endpoint, with periprocedural myocardial infarctions (MIs) systematically allocated to the PCI arm. We meta-analyzed the above RCTs for composite hard endpoints, with and without periprocedural MIs.

This study is registered in PROSPERO CRD42020166754 and follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration reporting. Patients had inducible ischemia, no left main disease nor severe left ventricular dysfunction.

Six RCTs involving 10,751 patients followed for a mean of 4.4 years were included. PCI+OMT versus OMT alone was associated with no difference in the two co-primary composite endpoints of all-cause death/MI/stroke and cardiovascular death/MI including all-MIs (IRR 0.99; 95% CI 0.90-1.08 and IRR 0.95; 95% CI 0.83-1.08 respectively). After inclusion of spontaneous rather than all-MIs (i.e., excluding periprocedural MIs), the odds showed benefit of PCI+OMT for both co-primary endpoints (IRR 0.88; 95% CI 0.80-0.97, P<0.01 and IRR 0.81; 95% CI 0.69-0.95, P=0.01 respectively) with numbers needed to treat of 42 in both cases.

Among CCS patients with inducible myocardial ischemia without severely reduced ejection fraction or left main disease, adding PCI to OMT reduces hard composite outcomes only after exclusion of periprocedural MIs. Continued efforts to define periprocedural MIs reproducibly, to assess their prognostic relevance and to prevent them are warranted.

Background Myocardial revascularization has been advocated to improve myocardial function and prognosis in ischemic cardiomyopathy (ICM). We discuss the evidence for revascularization in patients with ICM and the role of ischemia and viability detection in guiding treatment. Methods and Results We searched for randomized controlled trials evaluating the prognostic impact of revascularization in ICM and the value of viability imaging for patient management. Out of 1397 publications, 4 randomized controlled trials were included, enrolling 2480 patients. Three trials (HEART [Heart Failure Revascularisation Trial], STICH [Surgical Treatment for Ischemic Heart Failure], and REVIVED [REVascularization for Ischemic VEntricular Dysfunction]-BCIS2) randomized patients to revascularization or optimal medical therapy. HEART was stopped prematurely without showing any significant difference between treatment strategies. STICH showed a 16% lower mortality with bypass surgery compared with optimal medical therapy at a median follow-up of 9.8 years. However, neither the presence/extent of left ventricle viability nor ischemia interacted with treatment outcomes. REVIVED-BCIS2 showed no difference in the primary end point between percutaneous revascularization or optimal medical therapy. PARR-2 (Positron Emission Tomography and Recovery Following Revascularization) randomized patients to imaging-guided revascularization versus standard care, with neutral results overall. Information regarding the consistency of patient management with viability testing results was available in ≈65% of patients (n=1623). No difference in survival was revealed according to adherence or no adherence to viability imaging. Conclusions In ICM, the largest randomized controlled trial, STICH, suggests that surgical revascularization improves patients' prognosis at long-term follow-up, whereas evidence supports no benefit of percutaneous coronary intervention. Data from randomized controlled trials do not support myocardial ischemia or viability testing for treatment guidance. We propose an algorithm for the workup of patients with ICM considering clinical presentation, imaging results, and surgical risk.

(1) Background and Aim: Conflicting evidence exists regarding the benefits of percutaneous coronary intervention (PCI) on survival and symptomatic relief of patients with chronic coronary syndrome (CCS) compared with optimal medical therapy (OMT). This meta-analysis is to evaluate the short- and long-term clinical benefit of PCI over and above OMT in CCS. (2) Methods: Main endpoints were major adverse cardiac events (MACEs), all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), urgent revascularization, stroke hospitalization, and quality of life (QoL). Clinical endpoints at very short (≤3 months), short- (<12 months), and long-term (≥ 12 months) follow-up were evaluated. (3) Results: Fifteen RCTs with a total of 16,443 patients with CCS (PCI n = 8307 and OMT n = 8136) were included in the meta-analysis. At mean follow-up of 27.7 months, the PCI group had similar risk of MACE (18.2 vs. 19.2 %; p < 0.32), all-cause mortality (7.09 vs. 7.88%; p = 0.56), CV mortality (8.74 vs. 9.87%; p = 0.30), MI (7.69 vs. 8.29%; p = 0.32), revascularization (11.2 vs. 18.3%; p = 0.08), stroke (2.18 vs. 1.41%; p = 0.10), and hospitalization for anginal symptoms (13.5 vs. 13.9%; p = 0.69) compared with OMT. These results were similar at short- and long-term follow-up. At the very short-term follow-up, PCI patients had greater improvement in the QoL including physical limitation, angina frequency, stability, and treatment satisfaction (p < 0.05 for all) but such benefits disappeared at the long-term follow-up. (4) Conclusions: PCI treatment of CCS does not provide any long-term clinical benefit compared with OMT. These results should have significant clinical implications in optimizing patient's selection for PCI treatment.

For decades, the standard of care for stable ischemic heart disease (SIHD) has been an ischemia-centric approach based on largely observational data suggesting a survival benefit of revascularization in patients with moderate-or-severe ischemia. In this article, we will objectively review the evolution of the ischemia paradigm, the trial evidence comparing revascularization to medical therapy in SIHD, and what contemporary practice should be in 2022.

Randomized trials, including COURAGE and, most recently, the ISCHEMIA trial, have shown no reduction in "hard outcomes" like death and myocardial infarction (MI) in SIHD compared to medical therapy. The trial excluded high-risk patients with left main disease, low ejection fraction (EF) < 35%, and severe unacceptable angina. Irrespective of the severity of ischemia and the extent of coronary artery disease (CAD), revascularization did not offer any prognostic advantage over medical therapy. On the other hand, there was a durable improvement in symptoms. While there are many caveats to the ISCHEMIA trial, the overall strengths of the trial outweigh these limitations. The findings of ISCHEMIA are consistent with previous trials. It is time for the cardiology community to pivot towards medical therapy as the initial step for most patients with SIHD. Physicians should have the "COURAGE" to embrace "ISCHEMIA" and be comfortable with treating ischemia medically.

Whether percutaneous coronary intervention (PCI) improves clinical outcomes in patients with chronic angina and stable coronary artery disease (CAD) has been a continuing area of investigation for more than two decades. The recently reported results of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, the largest prospective trial of optimal medical therapy (OMT) with or without myocardial revascularization, provides a unique opportunity to determine whether there is an incremental benefit of revascularization in stable CAD patients.

Scientific databases and websites were searched to find randomized clinical trials (RCTs). Pooled risk ratios were calculated using the random-effects model.

Data from 10 RCTs comprising 12 125 patients showed that PCI, when added to OMT, were not associated with lower all-cause mortality (risk ratios, 0.96; 95% CI, 0.87-1.08), cardiovascular mortality (risk ratios, 0.91; 95% CI, 0.79-1.05) or myocardial infarction (MI) (risk ratios, 0.90; 95% CI, 0.78-1.04) as compared with OMT alone. However, OMT+PCI was associated with improved anginal symptoms and a lower risk for revascularization (risk ratios, 0.52; 95% CI, 0.37-0.75).

In patient with chronic stable CAD (without left main disease or reduced ejection fraction), PCI in addition to OMT did not improve mortality or MI compared to OMT alone. However, this strategy is associated with a lower rate of revascularization and improved anginal symptoms.

To review the current evidence for coronary revascularization in patients with diabetes mellitus (DM) in the setting of an acute coronary syndrome (ACS).

In patients with DM and stable multivessel ischemic heart disease, coronary artery bypass graft surgery (CABG) has been observed to be superior to percutaneous coronary intervention (PCI) in long-term follow-up, leading to lower rates of all-cause mortality, myocardial infarction, and repeat revascularization. In the ACS setting, PCI remains the most frequently performed procedure. In patients with an ST-segment-elevation myocardial infarction (STEMI), primary PCI should be the revascularization method of choice, whenever feasible. Controversy still exists regarding when and how to deal with possible residual lesions. In the non-ST-segment-elevation (NSTE) ACS setting, although there are no data from randomized controlled trials (RCTs), recent observational data and sub-analyses of randomized studies have suggested that CABG may be the preferred approach for patients with DM and multivessel coronary disease. There is a paucity of RCTs evaluating revascularization strategies (PCI and CABG) in patients with DM and ACS. CABG may be a viable strategy, leading to improved outcomes, especially following NSTE-ACS.

The guideline for coronary artery revascularization replaces the 2011 coronary artery bypass graft surgery and the 2011 and 2015 percutaneous coronary intervention guidelines, providing a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization as well as the supporting documentation to encourage their use.

A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered.

Coronary artery disease remains a leading cause of morbidity and mortality globally. Coronary revascularization is an important therapeutic option when managing patients with coronary artery disease. The 2021 coronary artery revascularization guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with coronary artery disease who are being considered for coronary revascularization, with the intent to improve quality of care and align with patients' interests.

This study explored the best treatment strategies for stable coronary artery disease (SCAD) patients with differing levels of ischemic severity.

We conducted a comprehensive search of the PubMed, EMBASE, and Cochrane databases - searching for relevant articles through 4 February 2021. We selected studies comparing different treatments for patients with SCAD who had received ischemia assessments. The primary outcome was death. The secondary outcomes were major adverse cardiovascular events (MACEs) and myocardial infarction (MI).

A total of 11 studies, including 35,607 subjects, were selected for this meta-analysis. Results showed that, compared with medical therapy, revascularization could reduce MACE incidence (odds ratio (OR) 0.73, 95% confidence interval (CI): 0.57-0.94, p < 0.05) in SCAD patients with myocardial ischemia, but that it was not effective for patients without ischemia. For mild ischemia, the incidence of death (OR 0.78, 95% CI: 0.59-1.01, p = 0.063), MACE (OR 0.91, 95% CI: 0.48-1.70, p = 0.762), or MI (OR 1.44, 95% CI: 0.94-2.19, p = 0.093) was the same whether they were treated with revascularization or medical therapy. For moderate to severe ischemia, revascularization reduced the incidence of MACE (OR 0.59, 95% CI: 0.42-0.83, p < 0.05) and MI (OR 0.83, 95% CI: 0.71-0.98, p < 0.05), but the incidence of death (OR 0.73, 95% CI: 0.47-1.12, p = .145) was similar. For SCAD patients with severe ischemia, revascularization may confer survival benefits (OR 0.46, 95% CI: 0.21-1.00, p = 0.05).

For SCAD patients with moderate to severe ischemia, revascularization reduces the MACE and MI incidences, but does not change the incidence of death. Evaluation for myocardial ischemia is vital when selecting a therapeutic strategy.

The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use.

A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use.

A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered.

Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

QAngio^® XA 3D/QFR^® (three-dimensional/quantitative flow ratio) imaging software (Medis Medical Imaging Systems BV, Leiden, the Netherlands) and CAAS^® vFFR^® (vessel fractional flow reserve) imaging software (Pie Medical Imaging BV, Maastricht, the Netherlands) are non-invasive technologies to assess the functional significance of coronary stenoses, which can be alternatives to invasive fractional flow reserve assessment.

The objectives were to determine the clinical effectiveness and cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR.

We performed a systematic review of all evidence on QAngio XA 3D/QFR and CAAS vFFR, including diagnostic accuracy, clinical effectiveness, implementation and economic analyses. We searched MEDLINE and other databases to January 2020 for studies where either technology was used and compared with fractional flow reserve in patients with intermediate stenosis. The risk of bias was assessed with quality assessment of diagnostic accuracy studies. Meta-analyses of diagnostic accuracy were performed. Clinical and implementation outcomes were synthesised narratively. A simulation study investigated the clinical impact of using QAngio XA 3D/QFR. We developed a de novo decision-analytic model to estimate the cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR relative to invasive fractional flow reserve or invasive coronary angiography alone. Scenario analyses were undertaken to explore the robustness of the results to variation in the sources of data used to populate the model and alternative assumptions.

Thirty-nine studies (5440 patients) of QAngio XA 3D/QFR and three studies (500 patients) of CAAS vFFR were included. QAngio XA 3D/QFR had good diagnostic accuracy to predict functionally significant fractional flow reserve (≤ 0.80 cut-off point); contrast-flow quantitative flow ratio had a sensitivity of 85% (95% confidence interval 78% to 90%) and a specificity of 91% (95% confidence interval 85% to 95%). A total of 95% of quantitative flow ratio measurements were within 0.14 of the fractional flow reserve. Data on the diagnostic accuracy of CAAS vFFR were limited and a full meta-analysis was not feasible. There were very few data on clinical and implementation outcomes. The simulation found that quantitative flow ratio slightly increased the revascularisation rate when compared with fractional flow reserve, from 40.2% to 42.0%. Quantitative flow ratio and fractional flow reserve resulted in similar numbers of subsequent coronary events. The base-case cost-effectiveness results showed that the test strategy with the highest net benefit was invasive coronary angiography with confirmatory fractional flow reserve. The next best strategies were QAngio XA 3D/QFR and CAAS vFFR (without fractional flow reserve). However, the difference in net benefit between this best strategy and the next best was small, ranging from 0.007 to 0.012 quality-adjusted life-years (or equivalently £140-240) per patient diagnosed at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year.

Diagnostic accuracy evidence on CAAS vFFR, and evidence on the clinical impact of QAngio XA 3D/QFR, were limited.

Quantitative flow ratio as measured by QAngio XA 3D/QFR has good agreement and diagnostic accuracy compared with fractional flow reserve and is preferable to standard invasive coronary angiography alone. It appears to have very similar cost-effectiveness to fractional flow reserve and, therefore, pending further evidence on general clinical benefits and specific subgroups, could be a reasonable alternative. The clinical effectiveness and cost-effectiveness of CAAS vFFR are uncertain. Randomised controlled trial evidence evaluating the effect of quantitative flow ratio on clinical and patient-centred outcomes is needed.

Studies are required to assess the diagnostic accuracy and clinical feasibility of CAAS vFFR. Large ongoing randomised trials will hopefully inform the clinical value of QAngio XA 3D/QFR.

This study is registered as PROSPERO CRD42019154575.

This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 56. See the NIHR Journals Library website for further project information.

Patients with left main, left main equivalent, and three-vessel coronary artery disease (CAD) represent an overlapping spectrum of patients with advanced CAD that is associated with an adverse prognosis. Guideline-directed medical therapy is a necessary but often insufficient treatment option, as such patients frequently need mechanical revascularization by either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). In patients with advanced CAD presenting with acute myocardial infarction, PCI, of course, is the preferred treatment option. For stable patients with advanced CAD, CABG surgery remains the standard of care. However, observations from the SYNergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) trial suggest that PCI may be a useful alternative in patients with three-vessel disease with a low SYNTAX score as well as in patients with left main disease and a low or intermediate SYNTAX score. In the subset of patients with diabetes mellitus, the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease trial unequivocally demonstrated the superiority of CABG surgery in improving outcomes. The findings of the recently published Everolimus-Eluting Stent System versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization and Nordic-Baltic-British Left Main Revascularization study trials point to a favorable role for PCI in certain low-to-moderate risk patients with left main stem disease.

Health-related quality of life (HRQOL) evaluation is an important measure of the impact of certain inerventions, epecially coronary artery diseases treatments. As more patients with acute coronary syndrome (ACS) live longer, doctors and researchers want to know how they manage in day-to-day life. The aim of this study was to compare costs and HRQOL of patients who underwent percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and medical therapy (MT) and to assess its main determinants in the whole sample of patients with ACS for a period of 12 months.

The study was carried out to estimate costs and HRQOL evaluation of 310 patients who underwent coronary revascularization (PCI, n = 139; CABG, n = 128; and MT, n = 43). We estimated direct costs (medical costs and nonmedical costs) and indirect costs (productivity losses owing to morbidity and mortality) based on a societal perspective, and HRQOL was assessed using the EQ-5D-3L (5 dimensions and 3 levels) and visual analog scale (VAS). We applied costs and HRQOL 1 month before treatment and 12 months after treatment in 3 groups, and scores were compared. Data entry and analysis were performed with SPSS.

Total EQ-5D index scores in PCI, CABG, and MT groups 1 month before treatment were 0.54 ± 0.26, 0.52 ± 0.25, and 0.56 ± 0.25, respectively. After 12 months, the HRQOL mean changed to 0.67 ± 0.20, 0.74 ± 0.15, and 0.65 ± 0.19, respectively, in PCI, CABG, and MT groups. The mean EQ-5D VAS score 1 month before treatment was 63 ± 15.4 for the PCI group, 62 ± 16.4 for the CABG group, and 64 ± 18.4 for the MT group; the mean EQ-5D VAS score 12 months after treatment was 74.8 ± 19.5 for the PCI group, 78.8 ± 18 for the CABG group, and 74 ± 19.7 for the MT group. All the 3 therapeutic strategies presented significant improvement in all dimensions of the follow-up. However, the CABG group was the one that had significantly greater improvement compared with PCI and MT. The mean (95% confidence interval) annual total cost for the overall sample was found to be $4940/patient. This cost was significantly higher among patients with CABG ($7327/patient) compared with PCI ($5225/patient) and MT ($2278/patient). Direct costs accounted for 87.7% and indirect costs for 12.3% of the total costs.

The quality of life was better in both CABG and PCI groups compared with MT after 1 year of follow-up. However, treatment with CABG is more difficult and expensive than PCI and MT, but it provides a better quality of life. The findings of the present study indicate the high economic burden of ACS in Iran.

The term "stable ischemic heart disease" includes a variety of clinical and pathophysiological situations resulting in different presentation modalities, often with complex referral patterns, and with multiple potential therapeutical options. Multifactorial pathogenesis and multiform expressivity are poorly captured by the traditional vision of ischemic heart disease (IHD) as the clogged pipes disease. The availability of different technologies for studying patients with symptoms suggestive of IHD, has shed a new light on the pathophysiology of the disease, but has also allowed appropriate follow-up of patients allocated to different therapeutical options. Though coronary revascularization has been one primary treatment option for obstructive coronary artery disease (CAD), the evidence for its efficacy in patients without acute presentation is far from optimal. A number of studies and meta-analyses strongly support the need for a personalized and optimized medical approach (including functional assessment and therapy) before the tailored option of revascularization in selected patients, in order to optimize its effects on symptoms and outcome. Most recent data have expanded the need for a more personalised approach to this complex situation, which should be patient-centered and not focused on technologies. In this review, we discuss the major pathophysiological factors and the most recent clinical data and guidelines suggestions, needed for a critical re-appraisal of the clinical decision-making to perform revascularization in patients with stable IHD. Moreover we aimed at suggesting the potential role for future studies to fill the existing knowledge gaps but also to counteract a reductive, hydraulic view of chronic IHD, which seems to be still alive and kicking, both in clinical and research communities, despite multiple evidences and recommendations.

Evaluation of hemodynamic parameters, such as fractional flow reserve (FFR), is recommended before percutaneous coronary intervention (PCI) for patients with angina pectoris (AP). However, the advantage of FFR-guided PCI has not been fully established. This study was performed to confirm whether FFR-guided PCI improves the prognosis compared with other treatments. Multiple databases were searched for studies published from 2000 to 2018, and a network meta-analysis (NMA) was performed to compare outcomes of FFR-guided PCI, non-FFR-guided PCI, coronary artery bypass grafting (CABG), and medical treatment (MT) for AP based on estimated odds ratios (ORs). The study included 18,093 patients from 15 randomized controlled trials (RCTs). No evidence of inconsistency was observed among the studies. The NMA showed that the all-cause mortality of FFR-guided PCI was not significantly different from that of the other treatment groups (CABG: OR, 1.1; 95% confidence interval [CI], 0.67-1.7; non-FFR-guided PCI: OR, 0.85; 95% CI, 0.53-1.4; and MT: OR, 0.83; 95% CI, 0.52-1.3). The NMA for the composite of all-cause mortality and myocardial infarction, which included 15,454 patients from 12 RCTs, showed that FFR-guided PCI significantly reduced the composite outcome compared with non-FFR-guided PCI and MT (non-FFR-guided PCI: OR, 0.66; 95% CI, 0.46-0.95 and MT: OR, 0.66; 95% CI, 0.46-0.95). Although FFR-guided PCI for AP did not show significant prognostic improvement compared with non-FFR-guided PCI, CABG, and MT, FFR-guided PCI may significantly reduce the composite of all-cause mortality and myocardial infarction compared with non-FFR-guided PCI and MT.

There has been a continuous debate about the survival benefit of percutaneous coronary intervention (PCI) for the management of patients with stable ischemic heart disease (SIHD) and moderate to severe ischemia. In this study we aimed to summarize the currently available evidence from randomized controlled trials (RCTs) on PCI versus medical therapy (MT) for patients with SIHD.

An electronic database search was conducted for RCTs that compared PCI on top of MT versus MT alone. A random effects model was used to calculate relative risk (RR) and 95% confidence intervals (CIs).

A total of 7 RCTs with 10,043 patients with a mean age of 62.54 ± 1.56 years and a median follow up of 3.9 years were identified. Among patients with SIHD and moderate to severe ischemia by stress testing, PCI didn't show any benefit for the primary outcome of all-cause mortality compared to MT(RR = 0.85; 95% CI 0.646-1.12; p = 0.639). There was also no benefit in cardiovascular (CV) death (RR = 0.88 ; 95% CI 0.71-1.09; p = 0.18) or myocardial infarction (MI) (RR = 0.271; 95% CI 0.782-1.087; P = 0.327) in the PCI group as compared to MT.

Among patients with SIHD and evidence of moderate to severe ischemia by stress testing, PCI on top of MT appears to add no mortality benefit as compared to with MT alone.

We conducted a systematic review and meta-analysis of contemporary randomized controlled trials (RCTs) to compare clinical outcomes among stable coronary artery disease (CAD) patients treated with revascularization [percutaneous coronary intervention (PCI), coronary-artery bypass grafting (CABG) or both] plus medical therapy (MT) versus MT alone.

Prospective RCTs were sought from MEDLINE, Embase, The Cochrane Library, and Web of Science up to April 2020. Data was extracted on study characteristics, methods, and outcomes. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled for the composite of all-cause mortality, myocardial infarction (MI), revascularizations, rehospitalizations, or stroke; its individual components and other cardiovascular endpoints.

Twelve unique RCTs comprising of 15,774 patients were included. There was no significant difference in all-cause mortality risk (0.95, 95% CI: 0.86-1.06); however, revascularization plus MT reduced the risk of the composite outcome of all-cause mortality, MI, revascularizations, rehospitalizations, or stroke (0.69, 95% CI: 0.55-0.87); unplanned revascularization (0.53, 95% CI: 0.40-0.71); and fatal MI (0.65, 95% CI: 0.49-0.84). Revascularization plus MT reduced the risk of stroke at 1 year (0.44, 95% CI: 0.30-0.65) and unplanned revascularization and the composite outcome of all-cause mortality, MI, revascularizations, rehospitalizations, or stroke at 2-5 years.

Revascularization plus MT does not confer survival advantage beyond that of MT among patients with stable CAD. However, revascularization plus MT may reduce the overall risk of the combined outcome of mortality, MI, revascularizations, rehospitalizations, or stroke, which could be driven by a decrease in the risk of unplanned revascularizations or fatal MI.

The definition of the high-risk chronic coronary syndrome varies depending on the noninvasive test used to trigger ischemia. The triggering occurs through increased myocardial work and oxygen demand, either through exercise or drugs. The initial approach to the chronic coronary syndrome leads us to discuss in which cases to prioritize an optimal initial medical therapy or to perform an initial invasive procedure of myocardial revascularization. In this article, we analyze both approaches based on previous studies carried out to date, where the initial invasive management has not been shown to be superior to initial optimal medical therapy in outcomes such as death or major adverse cardiovascular events.

With heighted interest in causal inference based on real-world evidence, this empirical study sought to understand differences between the results of observational analyses and long-term randomized clinical trials. We hypothesized that patients deemed "eligible" for clinical trials would follow a different survival trajectory from those deemed "ineligible" and that this factor could partially explain results. In a large observational registry dataset, we estimated separate survival trajectories for hypothetically trial-eligible vs ineligible patients under both coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI). We also explored whether results would depend on the causal inference method (inverse probability of treatment weighting vs optimal full propensity matching) or the approach to combine propensity scores from multiple imputations (the "across" vs "within" approaches). We found that, in this registry population of PCI/CABG multivessel patients, 32.5% would have been eligible for contemporaneous RCTs, suggesting that RCTs enroll selected populations. Additionally, we found treatment selection bias with different distributions of propensity scores between PCI and CABG patients. The different methodological approaches did not result in different conclusions. Overall, trial-eligible patients appeared to demonstrate at least marginally better survival than ineligible patients. Treatment comparisons by eligibility depended on disease severity. Among trial-eligible three-vessel diseased and trial-ineligible two-vessel diseased patients, CABG appeared to have at least a slight advantage with no treatment difference otherwise. In conclusion, our analyses suggest that RCTs enroll highly selected populations, and our findings are generally consistent with RCTs but less pronounced than major registry findings.

We aimed to evaluate the association of the prognostic impact of coronary revascularisation with physician-referred non-invasive diagnostic imaging tests (single photon emission CT (SPECT) vs coronary CT angiography) for coronary artery disease.

A post hoc analysis of a subgroup from the patient cohort recruited for the Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study.

Multiple centres in Japan.

From the data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred non-invasive imaging tests, 1205 patients with SPECT as an initial strategy and 625 with CT as an initial strategy were analysed. We assessed the effect of revascularisation (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata.

Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalisation for heart failure and late revascularisation, were followed up for 1 year. The χ² test, Student's t-test, Kaplan-Meier analysis, log-rank test and multivariable Cox proportional hazard model were used in data analysis.

A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularisation. Although in each stratum, the cumulative 1 year incidence of MACEs was significantly higher in patients who underwent revascularisation than in those who did not (SPECT stratum: 9.1 vs 1.2%, log-rank p<0.0001; CT stratum: 6.1 vs 0.8%, log-rank p=0.0001), there was no interaction between the risk of revascularisation and the imaging strata (SPECT stratum: adjusted HR (95% CI), 4.25 (1.86-9.72); CT stratum: 4.13 (1.16-14.73); interaction: p=0.97).

The association of revascularisation with the outcomes of patients with suspected coronary artery disease was not different between SPECT-first and CT-first strategies in a physician-referred fashion.

Revascularization is often performed in patients with stable ischemic heart disease. However, whether revascularization reduces death and other cardiovascular outcomes is uncertain.

We conducted PUBMED/EMBASE/Cochrane Central Register of Controlled Trials searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with stable ischemic heart disease. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina, and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials.

Fourteen randomized clinical trials that enrolled 14 877 patients followed up for a weighted mean of 4.5 years with 64 678 patient-years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function and low symptom burden, and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (relative risk [RR], 0.99 [95% CI, 0.90-1.09]). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary, indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced nonprocedural MI (RR, 0.76 [95% CI, 0.67-0.85]) but also with increased procedural MI (RR, 2.48 [95% CI, 1.86-3.31]) with no difference in overall MI (RR, 0.93 [95% CI, 0.83-1.03]). A significant reduction in unstable angina (RR, 0.64 [95% CI, 0.45-0.92]) and increase in freedom from angina (RR, 1.10 [95% CI, 1.05-1.15]) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke.

In patients with stable ischemic heart disease, routine revascularization was not associated with improved survival but was associated with a lower risk of nonprocedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these nonfatal spontaneous events improves long-term survival.

In patients with diabetes and multivessel coronary artery disease (CAD), the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial demonstrated that, on average, coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) for major acute cardiovascular events (MACE) and angina reduction. Nonetheless, multivessel PCI remains a common revascularization strategy in the real world.

To translate the results of FREEDOM to individual patients in clinical practice, risk models of the heterogeneity of treatment benefit were built.

Using patient-level data from 1,900 FREEDOM patients, the authors developed models to predict 5-year MACE (all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke) and 1-year angina after CABG and PCI using baseline covariates and treatment interactions. Parsimonious models were created to support clinical use. The models were internally validated using bootstrap resampling, and the MACE model was externally validated in a large real-world registry.

The 5-year MACE occurred in 346 (18.2%) patients, and 310 (16.3%) had angina at 1 year. The MACE model included 8 variables and treatment interactions with smoking status (c = 0.67). External validation in stable CAD (c = 0.65) and ACS (c = 0.68) demonstrated comparable performance. The 6-variable angina model included a treatment interaction with SYNTAX score (c = 0.67). PCI was never superior to CABG, and CABG was superior to PCI for MACE in 54.5% of patients and in 100% of patients with history of smoking.

To help disseminate the results of FREEDOM, the authors created a personalized risk prediction tool for patients with diabetes and multivessel CAD that could be used in shared decision-making for CABG versus PCI by estimating each patient's personal outcomes with both treatments.

Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are considered revascularization procedures, but only CABG can prolong life in stable coronary artery disease. Thus, PCI and CABG mechanisms may differ. Viability and/or ischemia detection to guide revascularization have been unable to accurately predict treatment effects of CABG or PCI, questioning a revascularization mechanism for improving survival. By contrast, preventing myocardial infarction may save lives. However, the majority of infarcts are generated by non-flow-limiting stenoses, but PCI is solely focused on treating flow-limiting lesions. Thus, PCI cannot be expected to significantly limit new infarcts, but CABG may do so through providing flow distal to vessel occlusions. All comparisons of CABG to PCI or medical therapy that demonstrate survival effects with CABG also demonstrate infarct reduction. Thus, CABG may differ from PCI by providing "surgical collateralization," prolonging life by preventing myocardial infarctions. The evidence is reviewed here.

In this chapter, we focus on evidences in current guidelines for treatment of coronary artery disease (CAD). In Part 1, diet and lifestyle management is discussed, which plays an important role in CAD risk control, including forming healthy dietary pattern, maintaining proper body weight, physical exercise, smoking cessation, and so on. Part 2 elaborated on revascularization strategies and medical treatments in patients presenting with acute coronary syndrome (ACS), including specific AHA and ESC guidelines on ST elevation myocardial infarction (STEMI) and non-ST elevation ACS (NSTE-ACS). Part 3 discussed chronic stable coronary artery disease (SCAD), the treatment objective of which is a combination of both symptomatic and prognostic improvement. Yet many of the recommendations for SCAD are expert-based rather than evidence-based. Initial medical treatment is safe and beneficial for most patients. While cumulating studies have focused on optimizing pharmacological therapy (referring to nitrates, beta-blockers, calcium channel blockers, antiplatelet agents, ACEI/ARB, statins, etc.), education, habitual modification, and social support matters a lot for reducing cardiac morbidity and mortality. Patients with moderate-to-severe symptoms and complex lesions should be considered for revascularization. But practical management of revascularization shall take individual characteristics, preference, and compliance into consideration as well.

Percutaneous coronary intervention is a common revascularisation technique. Serious complications are uncommon, but death is one of them. Seeking informed consent in advance of percutaneous coronary intervention is mandatory. Research shows that percutaneous coronary intervention patients have inaccurate perceptions of risks, benefits and alternative treatments.

To assess cardiologists' and patients' views about the informed consent process and anticipated treatment benefits.

Two cross-sectional, anonymous surveys were distributed in England: an electronic version to a sample of cardiologists and a paper-based version to patients recruited from 10 centres.