Fractional flow reserve versus angiography in guiding management to optimize outcomes in non-ST-elevation myocardial infarction (FAMOUS-NSTEMI): rationale and design of a randomized controlled clinical trial.

BACKGROUND: In patients with acute non-ST-elevation myocardial infarction (NSTEMI), coronary arteriography is usually recommended; but visual interpretation of the angiogram is subjective. We hypothesized that functional assessment of coronary stenosis severity with a pressure-sensitive guide wire (fractional flow reserve [FFR]) would have additive diagnostic, clinical, and health economic utility as compared with angiography-guided standard care. METHODS AND DESIGN: A prospective multicenter parallel-group 1:1 randomized controlled superiority trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% severity (threshold for FFR measurement) will be conducted. Patients will be randomized immediately after coronary angiography to the FFR-guided group or angiography-guided group. All patients will then undergo FFR measurement in all vessels with a coronary stenosis ≥30% severity including culprit and nonculprit lesions. Fractional flow reserve will be disclosed to guide treatment in the FFR-guided group but not disclosed in the "angiography-guided" group. In the FFR-guided group, an FFR ≤0.80 will be an indication for revascularization by percutaneous coronary intervention or coronary artery bypass surgery, as appropriate. The primary outcome is the between-group difference in the proportion of patients allocated to medical management only compared with revascularization. Secondary outcomes include the occurrence of cardiac death or hospitalization for myocardial infarction or heart failure, quality of life, and health care costs. The minimum and average follow-up periods for the primary analysis are 6 and 18 months, respectively. CONCLUSIONS: Our developmental clinical trial will address the feasibility of FFR measurement in NSTEMI and the influence of FFR disclosure on treatment decisions and health and economic outcomes.

Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.

BACKGROUND: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). METHODS: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. RESULTS: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. CONCLUSIONS: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. TRIAL REGISTRATION NUMBER: NCT01895751.

Invasive Versus Medical Management in Patients With Prior Coronary Artery Bypass Surgery With a Non-ST Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials. METHODS: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function). RESULTS: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years' follow-up (median [interquartile range], 744 [570-853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months. CONCLUSIONS: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751.

Successful reintroduction of previously failed ACE inhibitor therapy following stenting of atherosclerotic renovascular disease.

BACKGROUND: Angiotensin Converting Enzyme (ACE) inhibitors improve outcomes in patients with coronary artery disease irrespective of the status of the left ventricle. In the presence of functionally significant renovascular disease, ACE inhibitors often cause deterioration of renal function leading to their withdrawal. DESIGN: Observational study with 6 months prospective follow-up. METHODS AND RESULTS: Six patients with coronary artery disease and previous ACE inhibitor induced deterioration in renal function underwent renal artery stenting for angiographically-confirmed unilateral renal artery stenosis. Pre-existing significant renal dysfunction was present in 4 patients. Immediate technical success was achieved in all patients. ACE inhibitors were successfully reintroduced and titrated to maximum-tolerated in all 6 patients. At 6 months, one patient died due to progressive heart failure. The other patients remained tolerant of ACE inhibitor treatment with stable or improved renal function. CONCLUSION: Renal angiography should be considered in patients with coronary artery disease and ACE inhibitor induced renal dysfunction. Successful renal artery stenting permits reintroduction of ACE inhibitor with satisfactory maintenance of renal function at 6 months.

Functional result following direct coronary artery stenting with drug eluting stents in chronic stable angina is similar to stenting after balloon predilatation.

BACKGROUND: The safety and efficacy of direct coronary artery stenting without predilatation using drug eluting stents has not been firmly established. Concerns have been raised that this technique may be associated with increased risk of immediate and short term complications. METHODS: 68 consecutive patients with chronic stable angina and angiographically proven single vessel disease were randomised to undergo either direct coronary artery stenting or stenting after balloon predilation. All patients underwent Pressure Wire directed percutaneous coronary intervention (PCI) and drug eluting stents were deployed. Pre and post-PCI fractional flow reserve (FFR) was assessed following administration of intravenous adenosine. Post-procedure troponin I (TNI) and creatine kinase-MB (CK-MB) were compared. 51 of the 68 patients successfully completed a 6 month treadmill exercise test. RESULTS: There were no significant differences in the demographic, risk factor or angiographic profiles between the two groups except for hyperlipedemia and statin therapy. Drug eluting stents were deployed in all patients. Majority of the lesions were relatively simple (all lesions were either type A or B1). The pre-procedure FFR [mean(SD)]was marginally lower in the pre-dilatation group compared to the direct stenting group [0.57(0.17) versus 0.64(018); p=0.04]. The post-procedure FFR was similar in both groups [0.97(0.05) versus 0.98(0.03); p=0.26]. There was no difference in the post-procedure rise of either TNI or CK-MB in both groups. At 6 months, no major adverse cardiac events (death, MI or revascularisation) were observed in all patients. A positive exercise test was seen in 5 patients (10%) and there was no difference between the two groups. CONCLUSION: A strategy of direct stenting of appropriate coronary lesions with drug eluting stents in patients with chronic stable angina is associated with similar functional results as balloon predilatation followed by stenting.

Importance of collateral circulation in coronary heart disease.

AIMS: Collateral arteries are a common but inconsistent finding in coronary heart disease (CHD). We endeavoured to review the methods for coronary artery collateral assessment, the predictors and clinical importance of collateral blood flow, and the potential for therapeutic augmentation of collateral anastomoses. METHODS AND RESULTS: While many methods have been used to assess collateral blood flow only a few have been formally validated. Collateral flow index, as determined by measurement of intra-coronary pressure or flow velocity, is the most robust measure of collateral flow. These techniques have led to important advances in our understanding of collateral artery function. Coronary collateral arteries may prevent myocardial ischaemia in healthy subjects and in patients with CHD. A functional collateral circulation may lead to reduced ischaemia, preservation of ventricular function, and an improved prognosis. Recent trials have demonstrated that vascular progenitor cell therapies may improve ventricular function following acute myocardial infarction, raising the possibility of effective biological treatments to improve myocardial blood flow and prognosis in CHD. CONCLUSIONS: Coronary collateral anastomoses represent a prognostically important adaptive response in patients with CHD. Therapeutic augmentation of collaterals with emerging biological therapies represents a desirable goal for treating CHD patients.

Improvement in left ventricular function following successful rescue percutaneous coronary intervention is independent of time-to-reperfusion.

OBJECTIVE: To study the influence of clinical and angiographic factors on global and regional left ventricular (LV) function after rescue percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI). METHODS: We performed repeat cardiac catheterization in 102 patients who underwent rescue PCI at our centre. Eighty-two patients had suitable baseline and follow-up ventriculograms, which were analyzed offline by an automated edge detection technique. RESULTS: The mean (standard deviation [SD]) follow-up period was 22 (15) months. PCI was completed in all patients between 3 to 24 hours following the onset of pain. Improved global and regional LV systolic function was observed in 55 (67%) patients, and deterioration in 27 (33%). On univariate analysis, baseline ejection fraction (p = 0.005) and coronary stenting (p = 0.05) were associated with improved LV systolic function. Preprocedure TIMI flow, postprocedure TMP grade, time-to-reperfusion, and use of glycoprotein (GP) IIb/IIIa inhibitors did not influence LV systolic function. On multivariate analysis, ejection fraction at the time of rescue PCI (odds ratio [95% confidence interval]: 0.427 [0.234, 0.780]; p = 0.006) and stenting 3.944 (1.182, 13.156; p = 0.026) were predictors of improved LV systolic function. CONCLUSION: Successful rescue PCI was associated with improved LV function at follow up in the majority of patients. Stenting, but not GP IIb/IIIa inhibitor therapy, predicted improved LV function in the area supplied by the infarct-related artery. These improvements in regional wall motion were independent of the time taken to establish reperfusion, provided the intervention was carried out between 3 to 24 hours from the onset of pain.