Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Quality of Life After Fractional Flow Reserve-Guided PCI Compared With Coronary Bypass Surgery.

BACKGROUND: Previous studies have shown that quality of life improves after coronary revascularization more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the effect of fractional flow reserve guidance and current generation, zotarolimus drug-eluting stents on quality of life after PCI compared with CABG. METHODS: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) is a multicenter, international trial including 1500 patients with 3-vessel coronary artery disease who were randomly assigned to either CABG or fractional flow reserve-guided PCI. Quality of life was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire at baseline and 1 and 12 months. The Canadian Cardiovascular Class angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary end points included angina grade and work status. RESULTS: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference, 0.001 [95% CI, -0.016 to 0.017]; P=0.946). The trajectory of EQ-5D during the 12 months differed (P<0.001) between PCI and CABG: at 1 month, EQ-5D was 0.063 (95% CI, 0.047 to 0.079) higher in the PCI group. A similar trajectory was found for the EQ (EuroQol) visual analogue scale. The proportion of patients with Canadian Cardiovascular Class 2 or greater angina at 12 months was 6.2% versus 3.1% (odds ratio, 2.5 [95% CI, 0.96-6.8]), respectively, in the PCI group compared with the CABG group. A greater percentage of younger patients (<65 years old) were working at 12 months in the PCI group compared with the CABG group (68% versus 57%; odds ratio, 3.9 [95% CI, 1.7-8.8]). CONCLUSIONS: In the FAME 3 trial, quality of life after fractional flow reserve-guided PCI with current generation drug-eluting stents compared with CABG was similar at 1 year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those <65 years old. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Clinical Implications of Fractional Flow Reserve Measured Immediately After Percutaneous Coronary Intervention.

PURPOSE: The purpose of the present study was to find the independent predictors of Fractional Flow Reserve (FFR) measured immediately after percutaneous coronary intervention with drug-eluting stent implantation (post-PCI FFR) and investigate if applying vessel-specific post-PCI FFR cut-off values to predict target vessel failure (TVF), a composite of cardiac death (CD), non-fatal myocardial infarction (MI) and target vessel revascularization (TVR), or a composite of CD and MI ameliorated its predictive power. METHODS: Consecutive patients with post-PCI FFR measurement at our center between 2009 and 2021 were included in this analysis. RESULTS: A total of 434 patients with 500 vessels were included. Median pre-PCI FFR was 0.72 with no difference between LAD and non-LAD vessels. Median post-PCI FFR was 0.87. LAD location, male gender, smaller stent diameter, and lower pre-PCI FFR proved to be significant predictors of a lower post-PCI FFR. On a vessel-level, post-PCI FFR, stent length, and diabetes mellitus proved to be significant predictors of TVF and the composite of CD and MI. The best post-PCI FFR cut-off to predict TVF or a composite of CD and MI was 0.83 in the LAD and 0.91 in non-LAD vessels. CONCLUSION: LAD location is a predictor of a lower post-PCI FFR. Post-PCI FFR is an independent predictor of TVF as well as of the composite of CD and MI. No uniform target post-PCI FFR value exists; different cut-off values may have to be applied in LAD as opposed to non-LAD vessels.

Five-Year Outcomes with PCI Guided by Fractional Flow Reserve.

BACKGROUND: We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. METHODS: Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS: A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. CONCLUSIONS: In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

Changes in surgical revascularization strategy after fractional flow reserve.

AIMS: In the randomized GRAFFITI trial, surgeons drew their strategy based on coronary angiography. When patients were randomized to fractional flow reserve (FFR)-guidance, surgeons were informed of the FFR values and asked to redraw their strategy. The aim of this study was to investigate the changes induced by FFR knowledge. METHODS AND RESULTS: The intended and performed strategy (before and after FFR) were compared. Among 172 patients, 84 with 300 lesions were randomized to the FFR-guided group. The intended strategy was to bypass 236 stenoses:108 with a venous and 128 with an arterial graft. After disclosing FFR, a change in strategy occurred in 64 lesions (21.3%) of 48 (55%) patients. Among 64 lesions for which the intended strategy was medical therapy, 16 (25%) were bypassed after disclosing FFR. The number of procedures with >1 venous graft planned was significantly reduced from 37 to 27 patients (p = .031). The proportion of on-pump surgery was significantly reduced from 71 to 61 patients (p = .006). The rates of clinical events at 1 year were similar between patients with or without at least one change in strategy. DISCUSSION: FFR-guided CABG is associated with a simplified surgical procedure in 55% of the patients, with similar clinical outcomes.

Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct-related coronary artery improves outcomes. The use of PCI in non-infarct-related coronary arteries remains controversial. METHODS: We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct-related coronary artery in a 1:2 ratio to undergo complete revascularization of non-infarct-related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non-infarct-related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct-related coronary artery only. RESULTS: The primary outcome occurred in 23 patients in the complete-revascularization group and in 121 patients in the infarct-artery-only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval [CI], 0.22 to 0.55; P<0.001). Death occurred in 4 patients in the complete-revascularization group and in 10 patients in the infarct-artery-only group (1.4% vs. 1.7%) (hazard ratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR-related serious adverse event occurred in 2 patients (both in the group receiving infarct-related treatment only). CONCLUSIONS: In patients with STEMI and multivessel disease who underwent primary PCI of an infarct-related artery, the addition of FFR-guided complete revascularization of non-infarct-related arteries in the acute setting resulted in a risk of a composite cardiovascular outcome that was lower than the risk among those who were treated for the infarct-related artery only. This finding was mainly supported by a reduction in subsequent revascularizations. (Funded by Maasstad Cardiovascular Research and others; Compare-Acute ClinicalTrials.gov number, NCT01399736 .).

Fractional Flow Reserve and Quality-of-Life Improvement After Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease.

BACKGROUND: Whether the benefit in quality of life (QOL) after percutaneous coronary intervention depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown. This study sought to investigate the relationship between FFR values and improvement in QOL. METHODS: From the FAME 1 and 2 trials (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation), we identified 706 stable patients with coronary artery disease who had at least 1 lesion with an FFR≤0.80 that was treated with percutaneous coronary intervention and 185 patients with coronary artery disease who had no lesion with an FFR≤0.80 and were treated medically who served as a reference group. QOL was assessed by the European Quality of Life-5 Dimensions index at baseline, 1 month, and 1 year. We assessed the relationship between QOL improvement (defined as the change in European Quality of Life-5 Dimensions index from baseline) and FFR as a continuous value and according to abnormal FFR tertile. RESULTS: QOL improved significantly after percutaneous coronary intervention in each abnormal FFR tertile, whereas it did not change in the reference group. The lowest abnormal FFR subgroup had the greatest improvement in QOL at 1 month ( P<0.001). In mixed-effects models for repeated measures, lower FFR ( P=0.002 for 1 month and 0.049 for 1 year), greater delta FFR ( P=0.021 for 1 month and 0.025 for 1 year), and higher angina class ( P=0.001 for 1 month and <0.001 for 1 year) were associated with the greatest magnitude of QOL improvement at both 1 month and 1 year. CONCLUSIONS: Among patients with stable coronary artery disease, FFR and angina severity predict QOL improvement after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00267774 and NCT01132495.

Fractional flow reserve-guided PCI for stable coronary artery disease.

BACKGROUND: We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. METHODS: In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. RESULTS: The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. CONCLUSIONS: In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

Clinical value of post-percutaneous coronary intervention fractional flow reserve value: A systematic review and meta-analysis.

BACKGROUND: Fractional flow reserve (FFR) prior to percutaneous coronary intervention (PCI) is useful to guide treatment. Whether post-PCI FFR assessment might have clinical impact is controversial. The aim of this study is to evaluate the range of post-PCI FFR values and analyze the relationship between post-PCI FFR and clinical outcomes. METHODS: We systematically searched the PubMed, EMBASE, and Cochrane Library databases with cross-referencing of articles reporting post-PCI FFR and correlating post-PCI FFR values and clinical outcomes. The outcomes of interest were the immediate post-PCI FFR values and the correlations between post-PCI FFR and the incidence of repeat intervention and major adverse cardiac events (MACE). RESULTS: From 1995 to 2015, a total of 105 studies (n = 7470) were included, with 46 studies reporting post-PCI FFR and 59 studies evaluating relationship between post-PCI and clinical outcomes up to 30 months after PCI. Overall, post-PCI FFR values demonstrated a normal distribution with a mean value of 0.90 ± 0.04. There was a positive correlation between the percentage of stent use and post-PCI FFR (P < .0001). Meta-regression analysis indicated that higher post-PCI FFR values were associated with reduced rates of repeat intervention (P < .0001) and MACE (P = .0013). A post-PCI FFR ≥0.90 was associated with significantly lower risk of repeat PCI (odds ratio 0.43, 95% CI 0.34-0.56, P < .0001) and MACE (odds ratio 0.71, 95% CI 0.59-0.85, P = .0003). CONCLUSIONS: FFR measurement after PCI was associated with prognostic significance. Further investigation is required to assess the role of post-PCI FFR and validate cutoff values in contemporary clinical practice.

[The first 200 transcatheter aortic valve implantations in the Gottsegen Gyorgy Institute of Cardiology, Hungary]. / Az elso 200 transzkatéteres aortabillentyu-implantáció a Gottsegen György Országos Kardiológiai Intézetben.

INTRODUCTION: Transcatheter aortic valve implantation is a therapeutic alternative for contraindicated and high surgical risk patients with severe symptomatic aortic stenosis. This intervention is part of daily routine in the Institute of the authors. AIM: In the present work the results of the first 200 patients are discussed. METHOD: Until January, 2016, 200 patients (female 55%, mean age 79.9 years, average EuroSCORE 19.3%, left ventricular ejection fraction 54%, peak gradient 81.2 mmHg, mean aortic gradient 50.9 mmHg) underwent transcatheter aortic valve implantation. RESULTS: The procedure was performed with 99% success rate. Complications were evaluated according to VARC 2 definitions. Mortality was 5% at one month and 17.4% at one year. Cardiac mortality was 13.6 at one year. Cerebrovascular complications were 5% within one year, and 95% of patients were in NYHA I or II functional classes at one year. CONCLUSION: These findings are consistent with worldwide results. Orv. Hetil., 2016, 157(45), 1786-1792.

Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease.

BACKGROUND: The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone. METHODS: In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS: Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event. CONCLUSIONS: In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).

[Measurement of natriuretic peptides in heart failure: the good laboratory and clinical practice]. / Natriureticus peptidek mérése szívelégtelen betegekben: a helyes laboratóriumi és klinikai gyakorlat.

Cardiac natriuretic peptides (BNP, NT-proBNP) play a pivotal role in cardiovascular homeostasis, mainly due to their roles in vasodilatation, natriuresis, diuresis and due to their antiproliferative properties. Proper measurement of the natriuretic peptide levels may help differentiate between respiratory and cardiac forms of dyspnea, diagnose early forms of heart failure, evaluate severity of heart failure (prognosis) and monitor the efficacy of therapy. In many countries natriuretic peptide levels are being used as one of the earliest diagnostics tools to evaluate the involvement of the heart. Current theoretical and clinical data confirm the importance of natriuretic peptides in routine healthcare. These roles are clearly described in international recommendations and guidelines. In the current review the authors discuss the problems of the measurement of natriuretic peptides in Hungary, including several aspects related to laboratory medicine, cardiology and health economy.

[Percutaneous coronary intervention in stable coronary artery disease]. / Percutan coronariaintervenció stabil coronariabetegségben.

Percutaneous coronary intervention is a well-established symptomatic therapy of stable coronary artery disease. Using a literature search with special emphasis on the newly-published FAME 2 trial data, the author wanted to explore why percutaneous coronary intervention fails to reduce mortality and myocardial infarction in stable coronary artery disease, as opposed to surgical revascularisation. In the FAME 2 trial, fractional flow reserve-guided percutaneous coronary intervention with second generation drug eluting stents showed a significant reduction in the primary composite endpoint of 2-year mortality, myocardial infarction and unplanned hospitalization with urgent revascularisation as compared to medical therapy alone. In addition, landmark analysis showed that after 8 days, mortality and myocardial infarction were significantly reduced. The author concludes that percutaneous coronary intervention involving fractional flow reserve guidance and modern stents offers symptomatic, as well as prognostic benefit.

The pressure-derived microvascular resistance reserve and its correlation to Doppler MRR measurement-a proof of concept study.

Background: Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure. Purpose: We aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique. Methods: Hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRRp-3D). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRRp-3D. Results: In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpbmax and MRRp-3D (r 2 = 0.74, p < 0.0001). Using this relation (MRRp-3D = 1.04 + 0.51 × MRRpbmax), the linear prediction of the MRR was tested in the validation cohort of 19 measurements against the gold standard Doppler wire technique. A significant correlation was found between the linearly predicted and the measured values (r = 0.54, p = 0.01). If the area stenosis (AS%) was included to a quadratic prediction model, the correlation was improved (r = 0.63, p = 0.004). Conclusions: The MRR can be predicted reliably to assess microvascular function by our simple model. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement provides a simultaneous physiological assessment of the macro- and microvasculature.

Differential Impact of Fractional Flow Reserve Measured After Coronary Stent Implantation by Left Ventricular Dysfunction.

Background: Both left ventricular systolic function and fractional flow reserve (FFR) are prognostic factors after percutaneous coronary intervention (PCI). However, how these prognostic factors are inter-related in risk stratification of patients after PCI remains unclarified. Objectives: This study evaluated differential prognostic implication of post-PCI FFR according to left ventricular ejection fraction (LVEF). Methods: A total of 2,965 patients with available LVEF were selected from the POST-PCI FLOW (Prognostic Implications of Physiologic Investigation After Revascularization with Stent) international registry of patients with post-PCI FFR measurement. The primary outcome was a composite of cardiac death or target-vessel myocardial infarction (TVMI) at 2 years. The secondary outcome was target-vessel revascularization (TVR) and target vessel failure, which was a composite of cardiac death, TVMI, or TVR. Results: Post-PCI FFR was independently associated with the risk of target vessel failure (per 0.01 decrease: HRadj: 1.029; 95% CI: 1.009-1.049; P = 0.005). Post-PCI FFR was associated with increased risk of cardiac death or TVMI (HRadj: 1.145; 95% CI: 1.025-1.280; P = 0.017) among patients with LVEF ≤40%, and with that of TVR in patients with LVEF >40% (HRadj: 1.028; 95% CI: 1.005-1.052; P = 0.020). Post-PCI FFR ≤0.80 was associated with increased risk of cardiac death or TVMI in the LVEF ≤40% group and with that of TVR in LVEF >40% group. Prognostic impact of post-PCI FFR for the primary outcome was significantly different according to LVEF (Pinteraction = 0.019). Conclusions: Post-PCI FFR had differential prognostic impact according to LVEF. Residual ischemia by post-PCI FFR ≤0.80 was a prognostic indicator for cardiac death or TVMI among patients with patients with LVEF ≤40%, and it was associated with TVR among patients with patients with LVEF>40%. (Prognostic Implications of Physiologic Investigation After Revascularization with Stent [POST-PCI FLOW]; NCT04684043).

Functional Assessment of Long-Term Microvascular Cardiac Allograft Vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of death and retransplantation following heart transplantation (HTX). Surveillance angiography performed yearly is indicated for the early detection of the disease, but it remains of limited sensitivity. METHODS: We performed bolus thermodilution-based coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) measurements in HTX patients undergoing yearly surveillance coronary angiography without overt CAV. RESULTS: In total, 27 HTX patients were included who had 52 CFR, IMR, and FFR measurements at a mean of 43 months after HTX. Only five measurements were performed in the first year. CFR decreased significantly by 0.13 every year (p = 0.04) and IMR tended to increase by 0.98 every year (p = 0.051), whereas FFR did not change (p = 0.161) and remained well above 0.80 over time. After one year, CFR decreased significantly (p = 0.022) and IMR increased significantly (p = 0.015), whereas FFR remained unchanged (p = 0.72). CONCLUSIONS: The functional status of the epicardial coronary arteries of transplanted hearts did not deteriorate over time. On the contrary, a significant decrease in CFR was noted. In view of the increasing IMR, this is caused by the deterioration of the function of microvasculature. CFR and IMR measurements may provide an early opportunity to diagnose CAV.

Machine-learning-based prediction of fractional flow reserve after percutaneous coronary intervention.

BACKGROUND AND AIMS: Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) reflects residual atherosclerotic burden and is associated with future events. How much post-PCI FFR can be predicted based on baseline basic information and the clinical relevance have not been investigated. METHODS: We compiled a multicenter registry of patients undergoing pre- and post-PCI FFR. Machine-learning (ML) algorithms were designed to predict post-PCI FFR levels from baseline demographics, quantitative coronary angiography, and pre-PCI FFR. FFR deviation was defined as actual minus ML-predicted post-PCI FFR levels, and its association with incident target vessel failure (TVF) was evaluated. RESULTS: Median (IQR) pre- and post-PCI FFR values were 0.71 (0.61, 0.77) and 0.88 (0.84, 0.93), respectively. The Spearman correlation coefficient of the actual and predicted post-PCI FFR was 0.54 (95% CI: 0.52, 0.57). FFR deviation was non-linearly associated with incident TVF (HR [95% CI] with Q3 as reference: 1.65 [1.14, 2.39] in Q1, 1.42 [0.98, 2.08] in Q2, 0.81 [0.53, 1.26] in Q4, and 1.04 [0.69, 1.56] in Q5). A model with polynomial function of continuous FFR deviation indicated increasing TVF risk for FFR deviation ≤0 but plateau risk with FFR deviation >0. CONCLUSIONS: An ML-based algorithm using baseline data moderately predicted post-PCI FFR. The deviation of post-PCI FFR from the predicted value was associated with higher vessel-oriented event.

Clinical and Vessel Characteristics Associated With Hard Outcomes After PCI and Their Combined Prognostic Implications.

Background Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve measurement after drug-eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target-vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post-PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all P<0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; P=0.03) and vice versa (area under the curve 0.68 versus 0.78; P=0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; P for trend <0.01). Conclusions In patients undergoing drug-eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target-vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04684043. www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42021234748.

Applied coronary physiology for planning and guidance of percutaneous coronary interventions. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology.

The clinical value of fractional flow reserve and non-hyperaemic pressure ratios are well established in determining an indication for percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). In addition, over the last 5 years we have witnessed a shift towards the use of physiology to enhance procedural planning, assess post-PCI functional results, and guide PCI optimisation. In this regard, clinical studies have reported compelling data supporting the use of longitudinal vessel analysis, obtained with pressure guidewire pullbacks, to better understand how obstructive CAD contributes to myocardial ischaemia, to establish the likelihood of functionally successful PCI, to identify the presence and location of residual flow-limiting stenoses and to predict long-term outcomes. The introduction of new functional coronary angiography tools, which merge angiographic information with fluid dynamic equations to deliver information equivalent to intracoronary pressure measurements, are now available and potentially also applicable to these endeavours. Furthermore, the ability of longitudinal vessel analysis to predict the functional results of stenting has played an integral role in the evolving field of simulated PCI. Nevertheless, it is important to have an awareness of the value and challenges of physiology-guided PCI in specific clinical and anatomical contexts. The main aim of this European Association of Percutaneous Cardiovascular Interventions clinical consensus statement is to offer up-to-date evidence and expert opinion on the use of applied coronary physiology for procedural PCI planning, disease pattern recognition and post-PCI optimisation.