Instantaneous wave free ratio vs. fractional flow reserve and 5-year mortality: iFR SWEDEHEART and DEFINE FLAIR.

BACKGROUND AND AIMS: Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischaemia. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. The aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038). METHODS: Composite of major adverse cardiovascular events (MACE) and its individual components [all-cause death, myocardial infarction (MI), and unplanned revascularisation] were analysed. Raw Kaplan-Meier estimates, numbers at risk, and number of events were extracted at 5-year follow-up and analysed using the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA). RESULTS: In total, iFR and FFR-guided revascularization was performed in 2254 and 2257 patients, respectively. Revascularization was more often deferred in the iFR group [n = 1128 (50.0%)] vs. the FFR group [n = 1021 (45.2%); P = .001]. In the iFR-guided group, the number of deaths, MACE, unplanned revascularization, and MI was 188 (8.3%), 484 (21.5%), 235 (10.4%), and 123 (5.5%) vs. 143 (6.3%), 420 (18.6%), 241 (10.7%), and 123 (5.4%) in the FFR group. Hazard ratio [95% confidence interval (CI)] estimates for MACE were 1.18 [1.04; 1.34], all-cause mortality 1.34 [1.08; 1.67], unplanned revascularization 0.99 [0.83; 1.19], and MI 1.02 [0.80; 1.32]. CONCLUSIONS: Five-year all-cause mortality and MACE rates were increased with revascularization guided by iFR compared to FFR. Rates of unplanned revascularization and MI were equal in the two groups.

Validation of a semi-automatic software for optical coherence tomography - analysis in heart transplanted patients.

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3 months (3M) and 12 months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (ß-methodmean = - 0.289 mm2, p < 0.01; ß-methodmax = - 0.695 mm2, p < 0.01). Bland-Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (ß-methodmean = - 1.03 mm2, p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression.

Early and long-term prognosis in patients with remaining chronic total occlusions after revascularization attempt. A cohort study from the SKEJ-CTO registry.

OBJECTIVES: The present study aimed to compare safety and long-term prognosis of patients with chronic total coronary occlusions (CTO) stratified for remaining CTOs after percutaneous coronary intervention (PCI). DESIGN: The study cohort consisted of patients with coronary artery disease who underwent CTO PCI in a high volume tertiary center from 2009 to 2019 and were registered in Danish high-quality registers. Patients with successful PCI of all CTOs were compared to patients with ≥1 remaining CTO post-procedural. Primary endpoints were analysed using Cox-regression and Kaplan-Meier estimates, and included all-cause mortality, major adverse cardio- and cerebrovascular events (MACCE) and a 30-day safety endpoint. RESULTS: Procedural success rate was 87.7%, and 76.5% of patients had all CTO(s) opened post-PCI. Safety endpoint occurred in 4.6% of patients, and more frequently in patients with remaining CTO(s) (RD 4.9, 95%CI 0.1, 9.8). All-cause mortality was higher in patients with remaining CTO(s) (Unadjusted HR 1.65, 95% CI 1.03, 2.47, p = .015. Adjusted HR 1.32, 95%CI 0.88-1.99, p = .18) after eight years of follow-up. Risk of MACCE was significantly higher in patients with remaining CTO(s) (Unadjusted HR 1.79, 95% CI 1.34-2.41, p < .001. Adjusted HR 1.51, 95% CI 1.11-2.05, p = .009). CONCLUSIONS: In our centre, CTO PCI was associated with high success rate and low risk of 30-days complications. Presence of remaining CTO(s) after final revascularization attempt was associated with higher but statistically insignificant long-term mortality but was an independent predictor of MACCE.

Everolimus-eluting bioresorbable scaffold versus everolimus-eluting metallic stent in primary percutaneous coronary intervention of ST-segment elevation myocardial infarction: a randomized controlled trial.

BACKGROUND: Primary percutaneous coronary intervention with implantation of a metallic drug-eluting stent (DES) is the standard treatment for patients presenting with ST-elevation myocardial infarction (STEMI). Implantation of a bioresorbable scaffold (BRS) during STEMI represents a novel strategy without intravascular metal. OBJECTIVE: The aim of the study was to investigate 12-month healing response in an STEMI population after implantation of either the Absorb BRS or Xience DES (Abbott Vascular, USA). METHODS: The present trial was a prospective, randomized, controlled, nonblinded, noninferiority study with planned inclusion of 120 patients with STEMI. Patients were randomly assigned 1:1 to treatment with Absorb BRS or Xience DES. Implantation result and healing response were evaluated by angiography and optical coherence tomography (OCT) at baseline and 12-month follow-up. The primary endpoint was minimum flow area (MFA) assessed at 12 months. Coronary stent healing index (CSHI) was calculated from OCT images. RESULTS: Out of 66 included patients, 58 had follow-up OCT after 12 months, and 49 entered matched analysis. One death occurred in each group; none were stent-related. MFA was 5.13 ± 1.70 mm2 (95% CI, 4.44-5.82) in the BRS group compared with 6.30 ± 2.49 mm2 (95% CI, 5.22-7.37) (P = 0.06) in the DES group. Noninferiority could not be evaluated. CSHI for both groups had a median score of 3. CONCLUSION: The DES group performed numerically better in primary and secondary endpoints, but the CSHI showed good stent healing in both groups.

International randomized trial on the effect of revascularization or optimal medical therapy of chronic total coronary occlusions with myocardial ischemia - ISCHEMIA-CTO trial - rationale and design.

BACKGROUND: Chronic total occlusions (CTO) are frequent among patients with coronary artery disease. Revascularization with percutaneous coronary intervention (PCI) is safe and feasible in experienced hands. However, randomized data are needed to demonstrate symptomatic as well as prognostic effect of CTO-PCI compared to optimal medical therapy alone. METHODS: This trial aims to evaluate the effect of CTO PCI in patients with a CTO lesion and target vessel diameter ≥ 2.5 mm, and myocardial ischemia in the relevant territory. First, all patients are subjected to optimal medical therapy (OMT) for at least for 3 months and non-CTO lesions are managed according to guidelines. Subsequently, prior to randomization myocardial ischemia and quality of life (Seattle Questionnaire (SAQ)) is assessed. Patients are divided into two cohorts based on their SAQ score and randomized to either OMT alone or OMT and CTO-PCI. Cohort A is defined as Low- or asymptomatic patients with a quality-of-life score > 60 and/or CCS class < 2, and more than 10 % ischemia in the left ventricle (LV). Cohort B is symptomatic patients with a quality-of-life score < 60 or CCS class angina > 1 and at least ischemia in 5% of the LV. The primary end-point in cohort A is a composite of major adverse cardiac and cerebral events, hospitalization for heart failure and malignant ventricular arrhythmias. The primary endpoint in cohort B is difference in quality of life 6 months after randomization. IMPLICATIONS: This trial is designed to investigate if CTO-PCI improves QoL and MACCE. Both positive and negative outcome of the trial will affect future guidelines and recommendations on how to treat patients with CTO.

[Conservative versus invasive treatment of the patient with chronic occluded coronary arteries].

Patients with chronic total occluded coronary arteries (CTO) have worse prognosis than patients who do not have CTO. Medical therapy before embarking on invasive treatment is recommended. Invasive management with percutaneous coronary intervention or coronary artery bypass grafting is reserved for patients who receive medical treatment and have resistant angina and reversible ischaemia. Treatment should always be decided in collaboration with the patient, cardiologists, and cardio-thoracic surgeons. Follow-up treatment in the primary sector should include cardiac rehabilitation and reconsideration of medical therapy.

Cost-Effectiveness in Patients Undergoing Revascularization of Chronic Total Occluded Coronary Arteries-A Cohort Study.

Background: Revascularization of patients with chronic total occluded coronary arteries (CTO) is recommended if they have symptoms despite medical treatment. The cost-effectiveness of treatment with percutaneous coronary intervention (PCI) was investigated in this cohort study. Materials and Methods: The study was designed as a cohort study enrolling all patients undergoing PCI for a CTO in the Central Region of Denmark and recorded in the EUROCTO database. Major adverse cardio- and cerebrovascular events (MACCE) and admissions for cardiac symptoms were collected in the Western Denmark Heart Registry and through medical Journal Audits. Exposure was defined as successful revascularization of all CTO lesions compared with having one or more remaining CTOs after PCI attempt(s). Cost-effectiveness was evaluated as the net benefit (NB) at the patient level 3 years after treatment and through cost-effectiveness planes. The cost was defined as the cumulative cost of the index procedure and admissions due to MACCE and cardiac symptoms. Effectiveness was defined as the difference in MACCE for the primary analysis and the difference in death and symptomatic admissions for the secondary. Results: Between 2009 and 2019, 441 patients with ≥ 3 years of follow-up were treated with PCI for at least one CTO lesion (342 in the successful arm and 99 in the unsuccessful arm). The technical success rate was 85.4%. In total, 155 MACCE and 184 symptomatic admissions occurred in the follow-up period. The mean total cost was EUR 11.719 (11.034; 12.406) in the successful group vs. EUR 13.565 (11.899; 15,231) (p = 0.02) in the unsuccessful group. Net-benefit was EUR 1.846 (64; 3,627) after successful revascularization for MACCE. The adjusted analysis found an NB of EUR 1,481 (-118; 3,079). Bootstrap estimates showed cost-effectiveness planes in favor of successful revascularization. Conclusion: Patients fully revascularized for all CTO lesions had a more cost-efficient treatment. However, results need confirmation in a randomized controlled trial due to the risk of residual confounding after adjustment.

Impact of coronary plaque morphology on the precision of computational fractional flow reserve derived from optical coherence tomography imaging.

Background: Computational fractional flow reserve (FFR) was recently developed to expand the use of physiology-guided percutaneous coronary intervention (PCI). Nevertheless, current methods do not account for plaque composition. It remains unknown whether the numerical precision of computational FFR is impacted by the plaque composition in the interrogated vessels. Methods: This study is an observational, retrospective, cross-sectional study. Patients who underwent both optical coherence tomography (OCT) and FFR prior to intervention between August 2011 and October 2018 at Wakayama Medical University Hospital were included. All frames from OCT pullbacks were analyzed using a deep learning algorithm to obtain coronary plaque morphology including thin-cap fibroatheroma (TCFA), lipidic plaque volume (LPV), fibrous plaque volume (FPV), and calcific plaque volume (CPV). The interrogated vessels were stratified into three subgroups: the overestimation group with the numerical difference between the optical flow ratio (OFR) and FFR >0.05, the reference group with the difference ≥-0.05 and ≤0.05, and the underestimation group with the difference <-0.05. Results: In total 230 vessels with intermediate coronary artery stenosis from 193 patients were analyzed. The mean FFR was 0.82±0.10. Among them, 21, 179, and 30 vessels were in the overestimation, the reference, and the underestimation group, respectively. TCFA was higher in the underestimation group (60%) compared with reference (36.3%) and overestimation group (19%). Besides, it was not associated with numerical difference between OFR and FFR (NDOF) after multilevel linear regression. LPV was associated with NDOF as OFR underestimated FFR with -0.028 [95% confidence interval (CI): -0.047, -0.009] for every 100 mm3 increase in LPV. Conclusions: High lipid burden underestimates FFR when OFR is used to assess the hemodynamic importance of intermediate coronary artery stenosis. TCFA, FPV, and CPV were not independent predictors of NDOF.

Procedural findings and early healing response after implantation of a self-apposing bioresorbable scaffold in coronary bifurcation lesions.

We aimed to evaluate feasibility, early healing and self-correcting properties of the Desolve 150 bioresorbable scaffold (BRS) implanted in bifurcation lesions, using the simple, provisional side branch (SB) stenting technique. BIFSORB pilot was a proof-of-concept study enrolling 10 patients with stable angina pectoris and a bifurcation lesion with SB ≥ 2.5 mm and less than 50% diameter stenosis. Procedure and 1-month outcome was evaluated by optical coherence tomography (OCT) to assess scaffold performance and healing patterns. Nine patients were treated with Desolve 150 BRS and one delivery to the target bifurcation failed. Thrombus formation in the jailed SB ostium was seen in three cases, but was completely resolved at 1-month. OCT confirmed acute self-correcting properties. No clinical events were reported after six months. Scaffold diameter by OCT increased in the proximal main vessel from 3.09 ± 0.16 mm to 3.34 ± 0.18 mm (p = 0.01) and in distal main vessel from 2.82 ± 0.26 mm to 3.02 ± 0.29 mm (p < 0.01) at one-month follow-up. SB ostial diameter stenosis improved from 42 ± 15% to 34 ± 12% (p = 0.01). Malapposition was effectively reduced after 1 month from 4.1 (1.4; 6.1)% to 0.1 (0; 0.6)% (p = 0.002). Treatment of bifurcation lesions using Desolve 150 BRS was feasible except for a delivery failure and unsettling thrombus formation behind jailing SB struts, which was completely resolved at 1-month. Self-correcting and even self-expanding properties were confirmed.

Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study.

Objectives: We aimed to evaluate the mechanical properties and healing patterns 6 and 9 months after implantation of the sirolimus-eluting Fantom bioresorbable scaffold (BRS). Background: The Fantom BRS (Reva Medical, San Diego, USA) has differentiating properties including radiopacity, strut thickness of 125 µm, high expansion capacity and has demonstrated favourable mid-term clinical and angiographic outcomes. Methods and results: FANTOM II was a prospective, single arm study with implantation of the Fantom BRS in 240 patients with stable angina pectoris. Guidance by optical coherence tomography (OCT) was encouraged and was repeated at 6-month (cohort A) or 9-month follow-up (cohort B). Matched baseline and follow-up OCT recordings were available in 152 patients. In-scaffold mean lumen area in cohort A was 6.8±1.7 mm2 and 5.7±1.4 mm2 at baseline and follow-up (p<0.0001) and was 7.2±1.6 mm2 and 5.6±1.4 mm2 in cohort B (p<0.0001). Mean scaffold area remained stable from 7.1±1.5 mm2 at baseline to 7.2±1.4 mm2 at 6 months (p=0.12), and from 7.4±1.5 mm2 to 7.3±1.4 mm2 at 9 months. Strut malapposition was median 0.8 (IQR 0.0;3.5)% and 1.8 (IQR 0.3;6.0)% at baseline and was 0.0 (IQR 0.0;0.0)% in both groups at 6-month and 9-month follow-up. Strut tissue coverage was 98.1 (IQR 95.9;99.4)% at 6 months and 98.9 (IQR 98.3;100.0)% at 9 months. Conclusions: The novel Fantom BRS had favourable healing patterns at 6-month and 9-month follow-up as malapposition was effectively resolved and strut coverage was almost complete. The scaffold remained stable through follow-up with no signs of systematic late recoil.

Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study

OBJECTIVES: We aimed to evaluate the mechanical properties and healing patterns 6 and 9 months after implantation of the sirolimus-eluting Phantom bioresorbable scaffold (BRS). BACKGROUND: The Phantom BRS (Reva Medical, San Diego, USA) has differentiating properties including radiopacity, strut thickness of 125 µm, high expansion capacity and has demonstrated favorable mid-term clinical and angiographic outcomes. METHODS AND RESULTS: FANTOM II was a prospective, single arm study with implantation of the Phantom BRS in 240 patients with stable angina pectoris. Guidance by optical coherence tomography (OCT) was encouraged and was repeated at 6-month (cohort A) or 9-month follow-up (cohort B). Matched baseline and follow-up OCT recordings were available in 152 patients. In-scaffold mean lumen area in cohort A was 6.8±1.7 mm2 and 5.7±1.4 mm2 at baseline and follow-up (p<0.0001) and was 7.2±1.6 mm2 and 5.6±1.4 mm2 in cohort B (p<0.0001). Mean scaffold area remained stable from 7.1±1.5 mm2 at baseline to 7.2±1.4 mm2 at 6 months (p=0.12), and from 7.4±1.5 mm2 to 7.3±1.4 mm2 at 9 months. Strut malposition was median 0.8 (IQR 0.0;3.5)% and 1.8 (IQR 0.3;6.0)% at baseline and was 0.0 (IQR 0.0;0.0)% in both groups at 6-month and 9-month follow-up. Strut tissue coverage was 98.1 (IQR 95.9;99.4)% at 6 months and 98.9 (IQR 98.3;100.0)% at 9 months. CONCLUSIONS: The novel Phantom BRS had favorable healing patterns at 6-month and 9-month follow-up as malposition was effectively resolved and strut coverage was almost complete. The scaffold remained stable through follow-up with no signs of systematic late recoil. (AU)

Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II).

BACKGROUND: Quantitative flow ratio (QFR) is a novel diagnostic modality for functional testing of coronary artery stenosis without the use of pressure wires and induction of hyperemia. QFR is based on computation of standard invasive coronary angiographic imaging. The purpose of WIFI II (Wire-Free Functional Imaging II) was to evaluate the feasibility and diagnostic performance of QFR in unselected consecutive patients. METHODS AND RESULTS: WIFI II was a predefined substudy to the Dan-NICAD study (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease), referring 362 consecutive patients with suspected coronary artery disease on coronary computed tomographic angiography for diagnostic invasive coronary angiography. Fractional flow reserve (FFR) was measured in all segments with 30% to 90% diameter stenosis. Blinded observers calculated QFR (Medis Medical Imaging bv, The Netherlands) for comparison with FFR. FFR was measured in 292 lesions from 191 patients. Ten (5%) and 9 patients (5%) were excluded because of FFR and angiographic core laboratory criteria, respectively. QFR was successfully computed in 240 out of 255 lesions (94%) with a mean diameter stenosis of 50±12%. Mean difference between FFR and QFR was 0.01±0.08. QFR correctly classified 83% of the lesions using FFR with cutoff at 0.80 as reference standard. The area under the receiver operating characteristic curve was 0.86 (95% confidence interval, 0.81-0.91) with a sensitivity, specificity, negative predictive value, and positive predictive value of 77%, 86%, 75%, and 87%, respectively. A QFR-FFR hybrid approach based on the present results enables wire-free and adenosine-free procedures in 68% of cases. CONCLUSIONS: Functional lesion evaluation by QFR assessment showed good agreement and diagnostic accuracy compared with FFR. Studies comparing clinical outcome after QFR- and FFR-based diagnostic strategies are required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.