Development of machine learning models for fractional flow reserve prediction in angiographically intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. OBJECTIVES: We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. METHODS: Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables. RESULTS: A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off. CONCLUSIONS: ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR.

Implementation of Microcirculation Examination in Clinical Practice-Insights from the Nationwide POL-MKW Registry.

Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients' clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often.

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Second generation, sirolimus-eluting, bioresorbable Tyrocore scaffold implantation in patients with ST-segment elevation myocardial infarction: Baseline OCT and 30-day clinical outcomes - A FANTOM STEMI pilot study.

BACKGROUND: There is paucity of data on acute performance of Fantom (REVA Medical, CA), a second generation sirolimus-eluting bioresorbable scaffold (BRS), in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention. The aim of this study was to evaluate safety and efficacy of the Fantom BRS in the acute setting of STEMI characterized by thrombogenic milieu. METHODOLOGY: Ten STEMI patients treated with a sirolimus-eluting Fantom BRS were enrolled into prospective, observational study. The scaffold sizing, positioning, and optimization were optical coherence tomography (OCT) guided. The primary end-point was the device-oriented composite endpoint (DOCE), additionally angiographic and OCT analysis were performed. RESULTS: The primary-end point, defined as DOCE, did not occur in any patient within the 30-day follow-up. The procedural and angiographic success rates were both 100%, there was no case of scaffold thrombosis, target lesion revascularization nor death. In QCA, an in-device minimum lumen diameter was 2.89 ± 0.24 mm and the residual diameter stenosis was 3.56 ± 3.17%. OCT revealed an incomplete scaffold apposition in five patients with an average of seven malapposed struts per scaffold and mean distance of 120 ± 30 µm. There was no proximal edge dissection, the distal edge dissection was recorded in one patient. CONCLUSIONS: This is the first pilot study evaluating safety and efficacy of the Fantom BRS, a second generation fully bioresorbable coronary scaffold, in STEMI patients undergoing primary PCI with OCT guidance. Fantom BRS showed adequate safety and efficacy in the acute 30-day angiographic, OCT, and clinical follow-up.

Extracellular Matrix Proteomics Reveals Interplay of Aggrecan and Aggrecanases in Vascular Remodeling of Stented Coronary Arteries.

BACKGROUND: Extracellular matrix (ECM) remodeling contributes to in-stent restenosis and thrombosis. Despite its important clinical implications, little is known about ECM changes post-stent implantation. METHODS: Bare-metal and drug-eluting stents were implanted in pig coronary arteries with an overstretch under optical coherence tomography guidance. Stented segments were harvested 1, 3, 7, 14, and 28 days post-stenting for proteomics analysis of the media and neointima. RESULTS: A total of 151 ECM and ECM-associated proteins were identified by mass spectrometry. After stent implantation, proteins involved in regulating calcification were upregulated in the neointima of drug-eluting stents. The earliest changes in the media were proteins involved in inflammation and thrombosis, followed by changes in regulatory ECM proteins. By day 28, basement membrane proteins were reduced in drug-eluting stents in comparison with bare-metal stents. In contrast, the large aggregating proteoglycan aggrecan was increased. Aggrecanases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family contribute to the catabolism of vascular proteoglycans. An increase in ADAMTS-specific aggrecan fragments was accompanied by a notable shift from ADAMTS1 and ADAMTS5 to ADAMTS4 gene expression after stent implantation. Immunostaining in human stented coronary arteries confirmed the presence of aggrecan and aggrecan fragments, in particular, at the contacts of the stent struts with the artery. Further investigation of aggrecan presence in the human vasculature revealed that aggrecan and aggrecan cleavage were more abundant in human arteries than in human veins. In addition, aggrecan synthesis was induced on grafting a vein into the arterial circulation, suggesting an important role for aggrecan in vascular plasticity. Finally, lack of ADAMTS-5 activity in mice resulted in an accumulation of aggrecan and a dilation of the thoracic aorta, confirming that aggrecanase activity regulates aggrecan abundance in the arterial wall and contributes to vascular remodeling. CONCLUSIONS: Significant differences were identified by proteomics in the ECM of coronary arteries after bare-metal and drug-eluting stent implantation, most notably an upregulation of aggrecan, a major ECM component of cartilaginous tissues that confers resistance to compression. The accumulation of aggrecan coincided with a shift in ADAMTS gene expression. This study provides the first evidence implicating aggrecan and aggrecanases in the vascular injury response after stenting.

Safety and efficacy of self-apposing Stentys drug-eluting stent in left main coronary artery PCI: Multicentre LM-STENTYS registry.

BACKGROUND: There is a paucity of data on left main (LM) percutaneous coronary intervention (PCI) therapy with dedicated DES platforms. The LM-STENTYS is a multicenter registry aimed at evaluating clinical outcome after PCI of LM performed with a self-apposing Stentys DES implantation. METHODS: The registry consists of 175 consecutive patients treated with Stentys DES implanted to LM. The primary endpoint was the composite of major adverse cardiac and cerebral events (MACCE) defined as cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and stroke assessed after 1 year. The secondary endpoint was stent thrombosis (ST) at 1 year. RESULTS: The median age was 69 years (IQR, 62-78 years). Acute coronary syndrome (ACS) was the presenting diagnosis in 117 (66.9%) patients [74 (63.2%) unstable angina, 31 (26.5%) NSTEMI, 12 (10.3%) STEMI] and stable angina (SA) was present in 58 (33.1%) patients. The median SYNTAX score was 23.0 (IQR, 18.7-32.2) in the SA group and 25.0 (IQR, 20.0-30.7) in the ACS group. During 1-year follow-up in the SA group two (3.4%) MACCE occurred, both of them were cardiac deaths. In ACS patients there were 19 (16.2%) MACCE [9 (7.7%) cardiac deaths, 11 (9.4%) MIs, 11(9.4%) TLR, 1(0.9%) stroke]. Altogether, three (1.7%) cases of acute ST were noted, all of them in ACS subset. CONCLUSION: LM PCI using self-apposing Stentys DES showed favorable clinical outcomes at 1-year in patients with SA. Events of ST in the ACS group warrant further research.

An optical coherence tomography study of neointimal morphology and strut coverage at different time intervals from implantation of biodegradable polymer-coated sirolimus-eluting stents.

OBJECTIVES: The aim of the study was to capture the evolution of neointima after implantation of a biodegradable polymer-coated, sirolimus-eluting, cobalt-chromium coronary stent system (BP-DES). BACKGROUND: Optical coherence tomography (OCT) suggests that in-stent neointimal morphology influences clinical outcomes after DES implantation. METHODS: Sixty patients treated with single BP-DES implantation were examined by quantitative coronary angiography (QCA) and OCT at 3, 6, and 12-month follow-up. RESULTS: Median late lumen loss by QCA (mm) was 0.04 (IQR 0, 0.08), 0.17 (IQR 0, 0.32), and 0.14 (IQR 0.07, 0.31) at 3, 6, and 12-month follow-up respectively (P = 0.03). OCT cross-section multilevel analysis showed uncovered struts in 3.90%, 1.78%, and 0.02% of struts respectively (P = 0.03). The corresponding malapposition rates were 0.12%, 0.04%, and 0%. Lipid-rich neointima was observed only at 12-month follow-up in one restenotic lesion (0.77% cross-sections) that was accountable for the only target vessel revascularization. The homogeneous pattern was prevalent at all three time points, but its incidence displayed an upward trend (3 months: 59%; 6 months: 71%; 12 months: 88%) despite no difference in neointimal volume between 6 and 12 months. Conversely, a trend could be observed of decreasing incidence of heterogeneous pattern as the follow-up length increased. CONCLUSIONS: In this study of a single-type BP-DES, the majority of stent struts were covered within 3 months from implantation. While the quantitative neointimal accumulation plateaued at 6 months with no further significant increase beyond 6 months, the neointima continued to evolve qualitatively and mature along with better strut coverage between 6 and 12 months after implantation.

Gender differences and bleeding complications after PCI on first and second generation DES.

BACKGROUND: The aim of this study was to evaluate gender differences in the long-term clinical outcomes and safety of patients treated with first- and second generation DES. METHODS: The Katowice-Zabrze Registry included 1916 consecutive patients treated with either first or second generation DES. We evaluated major adverse cardiac and cerebrovascular events (MACCE) [composite of death, myocardial infarction (MI), stroke and target vessel revascularization (TVR)] at 12-month follow-up. Safety end point was bleeding complications and stent thrombosis. RESULTS: Registry included [unstable angina (UA) 1500(78%), non-ST-segment elevation myocardial infarction (NSTEMI) 285 (15%), ST-segment elevation myocardial infarction/left bundle branch block (STEMI/LBBB) 131 (7%)]. There were 35.5% females and 64.5% males. Women were older and had higher prevalence of comorbidities. Males more often had multivessel disease and higher Syntax score when comparable to females. We did not observed difference in acute and subacute stent thrombosis in our data, however, females had more in-hospital bleeding complications. Univariable Cox regression analysis revealed that women had similar outcomes when compared to men in terms of a risk of death, MI, TVR, stroke and MACCE at 1-year follow-up. There were no differences between males and females in MACCE when first- and second generation DES were analyzed separately. CONCLUSION: Despite higher risk profile, women treated with DES have similar outcomes as males in 1-year follow-up. However there is, an increased risk of in-hospital bleedings in women.

Second-generation drug-eluting stents in the elderly patients with acute coronary syndrome: the in-hospital and 12-month follow-up of the all-comer registry.

BACKGROUND: Katowice-Zabrze registry provides data that can be used to evaluate clinical outcomes of percutaneous coronary interventions in elderly patients (≥70 y/o) treated with either first- (DES-I) or second-generation (DES-II) drug-eluting stents (DES). METHODS: The registry consisted of data from 1916 patients treated with coronary interventions using either DES-I or DES-II stents. For our study, we defined patients ≥70 years of age as elderly. We evaluated any major adverse cardiac and cerebral events (MACCE) at 12-month follow-up. RESULTS: Coronary angiography revealed a higher incidence of multivessel coronary artery disease in this elderly patient population. There were no differences in acute and subacute stent thrombosis (0.4 vs. 0.6%, p = 0.760; 0.4 vs. 0.4%; p = 0.712). Elderly patients experienced more in-hospital bleeding complications requiring blood transfusion (2.0 vs. 0.9%; p = 0.003). Resuscitated cardiac arrests (2.0 vs. 0.9%; p = 0.084) were observed more often in this elderly patients during hospitalization. The composite in-hospital MACCE rates did not differ statistically between both groups (1.4 vs. 1.1%; p = 0.567). Data from a twelve-month follow-up disclosed that mortality was higher (7.1 vs. 1.8%; p < 0.001) in the elderly, with no difference in TVR (7.2 vs. 9.9%, p = 0.075), MI (6.0 vs. 4.8%, p = 0.300), stroke (0.8 vs. 0.6%, p = 0.600) and composite MACCE (15.0 vs. 13.4%, p = 0.324). The age of 70 years or over was an independent predictor of death [HR = 2.55 (95% CI 1.49-4.37); p < 0.001]. The use of DES-II reduced the risk of MI [HR = 0.40 (95% CI 0.19-0.82); p = 0.012] in the elderly. CONCLUSION: This elderly patient population had an increased risk of in-hospital bleeding complications requiring blood transfusion and a higher risk of death at 12-month follow-up. The use of new-generation DES reduced the risk of MI in the elderly population.

Multiplug paravalvular leak closure using Amplatzer Vascular Plugs III: A prospective registry.

BACKGROUND: Transcatheter paravalvular leak closure (TPVLC) offers a viable alternative to reoperation but optimal technical strategy is still to be defined. We present a prospective TPVLC registry in which safety and efficacy of multi-plug, single-stage approach were assessed. METHODS: Patients with heart failure (HF) symptoms caused by PVL were qualified for TPVLC by Heart Team. Ante- or retrograde access was employed for mitral while retrograde only for aortic PVLs. Two to 4 AVP 3 devices were simultaneously implanted into each PVL. Endpoints were defined according to VARC-2. RESULTS: From 64 referred patients 49, with either mechanical valves (n = 30) or stented bioprostheses, were eligible for TPVLC. PVL location was mitral (n = 29) or aortic (n = 20). In aortic group acute procedural success (APS) ratio was 100% and no MACCEs occurred. In mitral group, first-attempt TPVLC was successful in 22 cases (4/4 in transapical and 18/25 in transseptal access). Second-attempt transapical procedure followed transseptal failure in 5 patients. Mitral TPVLC ultimately proved efficient in 89.7% with 76.5% APS. Cumulatively, TPVLC was accomplished in 46 subjects (93.9%) with 78% APS. When successful, it led to a significant decrease of NT-proBNP concentration and HF symptoms regression. Periprocedural safety endpoints were met in three patients and included non-disabling stroke, and two access site-related complications. In device failure group two patients died (end-stage HF) and two others were rehospitalized. CONCLUSION: TPVLC with simultaneous deployment of multiple AVP III occluders is feasible with high device success rate and no significant periprocedural complications. The clinical benefits of reduction of HF symptoms and hemolysis are evident after 30 days and persist up to 1 year without recurrence of PVL.

Optical Coherence Tomography of De Novo Lesions and In-Stent Restenosis in Coronary Saphenous Vein Grafts (OCTOPUS Study).

BACKGROUND: The OCTOPUS registry prospectively evaluates the procedural and long-term outcomes of saphenous vein graft (SVG) PCI. The current study assessed the morphology of de novo lesions and in-stent restenosis (ISR) in patients undergoing PCI of SVG. METHODS AND RESULTS: Optical coherence tomography (OCT) of SVG lesions in consecutive patients presenting with stable CAD and ACS was carried out. Thirty-nine patients (32 de novo and 10 ISR lesions) were included in the registry. ISR occurred in 5 BMS and 5 DES. There were no differences in the presence of plaque rupture and thrombus between de novo lesions and ISR. Lipid-rich tissue was identified in both de novo lesions and in ISR (75% vs. 50%, P=0.071) with a higher prevalence in BMS than in DES (23% vs. 7.5%; P=0.048). Calcific de novo lesions were detected in older grafts as compared with non-calcific atheromas (159±57 vs. 90±62 months after CABG, P=0.001). Heterogeneous neointima was found only in ISR (70% vs. 0, P<0.001) and was observed with similar frequency in both BMS and DES (24% vs. 30%, P=0.657). ISR was detected earlier in DES than BMS (median, 50 months; IQR, 18-96 months vs. 27 months; IQR, 13-29 months, P<0.001). CONCLUSIONS: OCT-based characteristics of de novo and ISR lesions in SVG were similar except for heterogeneous tissue, which was observed only in ISR. (Circ J 2016; 80: 1804-1811).

A 12-month angiographic and optical coherence tomography follow-up after bioresorbable vascular scaffold implantation in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: The aim of the study was to evaluate the healing process at 12 months after ABSORB™ bioresorbable vascular scaffold (BVS) implantation in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: There is currently no data on long-term BVS performance in the acute thrombotic setting. The underlying altered plaque pathomorphology may impact the neointima healing pattern, potentially making it different to that observed in stable coronary artery disease (CAD). METHODS: We have performed an angiographic and optical coherence tomography (OCT) 12-month follow-up of 19 STEMI patients who were treated with a BVS implantation (23 scaffolds). An independent core laboratory performed a paired analysis of the corresponding frames at baseline and follow-up. RESULTS: At 12 months, the OCT follow-up showed a decrease in the mean lumen area (8.29 ± 1.53 mm(2) vs. 6.82 ± 1.57 mm(2) , P < 0.001), but no significant change in the mean scaffold area (8.49 ± 1.53 mm(2) vs. 8.90 ± 1.51 mm(2) ). Significant decreases in malapposed strut ratio (4.9 ± 8.65% vs. 0.4 ± 1.55%, P < 0.001) and malapposition area (0.29 ± 0.60 mm(2) 0.08 ± 0.32 mm(2) , P = 0.002) were observed. A nonhomogenous proliferation of neointima was revealed with a symmetry index of 0.15 (0.08-0.27), a mean neointima thickness of 203 µm (183-249) and mean neointima area of 2.07 ± 0.51 mm(2) . The quantitative coronary angiography showed late lumen loss of 0.08 ± 0.23 mm and no significant change in the minimal lumen diameter (P = 0.11). There were no major adverse cardiovascular events (MACE), except for one nontarget vessel revascularization. CONCLUSIONS: The OCT revealed a favorable healing pattern after BVS implantation in a STEMI population.

Current role of intravascular imaging in percutaneous treatment of calcified coronary lesions.

Percutaneous treatment of calcified coronary lesions is still a challenge in modern interventional cardiology practice. Coronary angiography is limited to the precise and quantitative assessment of calcium in coronary arteries. Intracoronary imaging (ICI) modalities, including optical coherence tomography (OCT) and intravascular ultrasound (IVUS), produce a very detailed image of calcifications and could help in proper percutaneous treatment. Intracoronary imaging indicates the need to use additional tools and improves the final effect of an intervention. Drawing on the already published literature, the authors focused on the qualification of patients to the procedure, conduct and result of interventional procedures involving calcified lesions supported by ICI. The article shows the advantages and disadvantages of both ICI methods in general and especially in calcified lesions. Currently available tools dedicated to dealing with coronary calcium and helping to meet optimal stent implantation criteria are also described. This article reviews the data on ICI implementation in daily clinical practice to improve the results of percutaneous interventions, and indicates further directions.

The characteristic of acute coronary syndromes of patients with multivessel coronary artery disease in centers with and without cardiac surgery on-site.

BACKGROUND: Multivessel disease (MVD) is diagnosed in a fair number of patients with acute coronary syndrome (ACS). There are 36 cardiac-surgery (CS) centres and 157 catheterization laboratories dedicated to treat ACS in Poland. The aim of the study was to analyze MVD patient outcomes presented with ACS in centers with or without CS on-site. METHODS: The present study is a retrospective analysis (2017-2020) of MVD ACS patients (n = 4618) outcomes between those treated in centers with CS on site (n = 595) and those without CS (n = 4023). RESULTS: Patients in CS centers had a higher prevalence of renal failure (13.3% vs. 8.8%, p ≤ 0.001) and a more frequent history of coronary angioplasty - percutaneous coronary intervention (18.9% vs. 14.4%, p = 0.005). During the coronary angiography a femoral artery access was more often used in CS center patients (47.1% vs. 15.2%, p < 0.001). Percutaneous coronary intervention of MVD was more often performed in CS centers (74.6% vs. 71.0%, p = 0.054). In-hospital death (7.6% vs. 4.6%, p = 0.002), reinfarction (1.1% vs. 0.1%, p < 0.001), hemorrhagic complications (6.4% vs. 1.6%, p < 0.001), recurrent target vessel revascularization (1.8% vs. 0.4%, p ≤ 0.001) and pulmonary edema (3.7% vs. 1.5%, p < 0.001) occurred more often in CS centers. CONCLUSIONS: The safety of ACS treatment in MVD patients in centers without CS on site is non-inferior to their treatment in centers with CS on site. Interestingly, there were more in-hospital adverse events observed in ACS MVD patients treated in centers with CS.

Increased Incidence of Adverse Events in Diabetes Mellitus Patients with Combined Multiple Vulnerable Plaque Features. New Insights From the COMBINE OCT-FFR trial.

AIMS: To evaluate the individual as well as combined impact of OCT-detected vulnerability features (OCT-VFs) in the prediction of major adverse cardiovascular events (MACE) in non-ischemic lesions in patients with diabetes mellitus (DM). METHODS AND RESULTS: The COMBINE OCT-FFR (NCT02989740) was a prospective, double-blind, international, natural history study that included patients with DM having ≥1 lesions with a fractional flow reserve >0.80, undergoing systematic OCT assessment. Pre-specified OCT-VFs included TCFA, r-MLA, h-PB, and CP. The primary endpoint (MACE) was a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or hospitalization for unstable angina up to 5 years, analyzed according to the presence of these OCT-VFs, both individually and in combination. TCFA, r-MLA, h-PB and CP were identified in 98 (25.1%), 159 (40.8%), 56 (14.4%), and 116 (29.8%) patients, respectively. The primary endpoint rate increased progressively from 6.9% to 50.0% (HR=10.10; 95%CI, 3.37 to 30.25, p<0.001) in patients without OCT-VFs compared to those with concomitant h-PB, r-MLA, CP, and TCFA. Importantly, while TCFA, h-PB, r-MLA and CP were individually associated with the primary endpoint, the presence of two or more OCT-VFs significantly increased the likelihood of adverse events at 5 years. CONCLUSIONS: In patients with DM and non-ischemic lesions, TCFA, h-PB, r-MLA and CP were predictors of adverse events. However, the presence of two or more OCT-VFs significantly increased the likelihood of MACE at 5 years. Further studies are warranted to confirm these findings and their potential clinical implications in a randomized fashion.

Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial.

BACKGROUND: Thin-cap fibroatheroma (TCFA) lesions are associated with a high risk of future major adverse cardiovascular events. However, the impact of other optical coherence tomography-detected vulnerability features (OCT-VFs) and their interplay with TCFA in predicting adverse events remains unknown. AIMS: We aimed to evaluate the individual as well as the combined prognostic impact of OCT-VFs in predicting the incidence of the lesion-oriented composite endpoint (LOCE) in non-ischaemic lesions in patients with diabetes mellitus (DM). METHODS: COMBINE OCT-FFR (ClinicalTrials.gov: NCT02989740) was a prospective, double-blind, international, natural history study that included DM patients with ≥1 non-culprit lesions with a fractional flow reserve>0.80 undergoing systematic OCT assessment. OCT-VFs included the following: TCFA, reduced minimal lumen area (r-MLA), healed plaque (HP), and complicated plaque (CP). The primary endpoint, LOCE - a composite of cardiac mortality, target vessel myocardial infarction, or clinically driven target lesion revascularisation up to 5 years - was analysed according to the presence of these OCT-VFs, both individually and in combination. RESULTS: TCFA, r-MLA, HP and CP were identified in 98 (25.3%), 190 (49.0%), 87 (22.4%), and 116 (29.9%) patients, respectively. The primary endpoint rate increased progressively from 6.3% to 55.6% (hazard ratio 15.2, 95% confidence interval: 4.53-51.0; p<0.001) in patients without OCT-VFs as compared to patients with concomitant HP, r-MLA, CP, and TCFA. The coexistence of TCFA with other OCT-VFs resulted in an increased risk of the LOCE at 5 years. CONCLUSIONS: In DM patients with non-ischaemic lesions, TCFA was the strongest predictor of future LOCE events. However, lesions that present additional OCT-VFs are associated with a higher risk of adverse events than OCT-detected TCFA alone. Further randomised studies are warranted to confirm these findings and their potential clinical implications.

Optical Coherence Tomography Measures Predicting Fractional Flow Reserve: The OMEF Study.

Background: Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to evaluate the value of OCT in predicting fractional flow reserve (FFR). Methods: We performed a multicenter, international, pooled analysis of individual patient-level data from published studies assessing FFR and OCT on the same vessel. Data from stable or unstable patients who underwent both FFR and OCT of the same coronary artery were collected through a dedicated database. Predefined OCT parameters were minimum lumen area (MLA), percentage area stenosis (%AS), and presence of thrombus or plaque rupture. Primary end point was FFR ≤0.80. Secondary outcome was the incidence of major adverse cardiac events in patients not undergoing revascularization based on negative FFR (>0.80). Results: A total of 502 coronary lesions in 489 patients were included. A significant correlation was observed between OCT-MLA and FFR values (R = 0.525; P < .001), and between OCT-%AS and FFR values (R = -0.482; P < .001). In Receiver operating characteristic analysis, MLA <2.0 mm2 showed a good discriminative power to predict an FFR ≤0.80 (AUC, 0.80), whereas %AS >73% showed a moderate discriminative power (AUC, 0.73). When considering proximal coronary segments, the best OCT cutoff values predicting an FFR ≤0.80 were MLA <3.1 mm2 (AUC, 0.82), and %AS >61% (AUC, 0.84). In patients with a negative FFR not revascularized, the combination of lower MLA and higher %AS had a trend toward worse outcome (which was statistically significant in the analysis restricted to proximal vessels). Conclusions: OCT lumen measures (MLA, %AS) may predict FFR, and different cutoffs are needed for proximal vessels.

Medically Treated Nonischemic Thin-Cap Fibroatheroma Lesions Versus Fractional Flow Reserve-Guided Complete Revascularization in Diabetic Patients.

Background: Fractional flow reserve (FFR) is an established method to guide decisions on revascularization; however, in patients with diabetes mellitus (DM), FFR-negative lesions carrying an optical coherence tomography-detected thin-cap fibroatheroma (TCFA) remain at high risk for adverse cardiac events. Methods: In this prespecified subanalysis of the COMBINE OCT-FFR trial, DM patients with ≥1 FFR-negative, TCFA-positive medically treated target lesions referred to as vulnerable plaque (VP group), were compared to patients with exclusively FFR-positive target lesions who underwent complete revascularization (CR group). The primary endpoint was first and recurrent event analysis for target lesion failure and the secondary endpoint was a composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, or hospitalization due to unstable angina. Results: Among 550 patients enrolled, 98 belonged to the VP group while 93 to the CR group and were followed up to 5 years. The VP group had a higher occurrence of the primary endpoint (20.4% vs 8.6%; HR, 2.22; 95% CI, 0.98-5.04; P = .06). Recurrent event analysis showed that the VP group had significantly higher rates of the primary and secondary endpoints (9.17 vs 3.76 events per 100 PY; RR, 2.44; 95% CI, 1.16-5.60; P = .01 and 13.45 vs 5.63 events per 100 PY; RR, 2.39; 95% CI, 1.30-4.62; P < .01). Conclusions: In a population with DM, medically treated nonischemic, TCFA-carrying target lesions were associated with higher risk of reoccurring adverse cardiac events compared to target lesions that underwent complete revascularization, opening the discussion about whether a focal preventive revascularization strategy could be contemplated for highly vulnerable lesions.

Sex differences in plaque characteristics of fractional flow reserve-negative non-culprit lesions after myocardial infarction.

BACKGROUND AND AIMS: Recurrent events after myocardial infarction (MI) are common and often originate from native non-culprit (NC) lesions that are non-flow limiting. These lesions consequently pose as targets to improve long-term outcome. It is, however, largely unknown whether these lesions differ between sexes. The aim of this study was to assess such potential differences. METHODS: From the PECTUS-obs study, we assessed sex-related differences in plaque characteristics of fractional flow reserve (FFR)-negative intermediate NC lesions in 420 MI-patients. RESULTS: Among the included patients, 80 (19.1 %) were female and 340 (80.9 %) male. Women were older and more frequently had hypertension and diabetes. In total, 494 NC lesions were analyzed. After adjustment for clinical characteristics and accounting for within-patients clustering, lesion length was longer in female patients (20.8 ± 10.0 vs 18.3 ± 8.5 mm, p = 0.048) and minimum lumen area (2.30 ± 1.42 vs 2.78 ± 1.54 mm2, p < 0.001) and minimum lumen diameter (1.39 ± 0.45 vs 1.54 ± 0.44 mm, p < 0.001) were smaller. The minimum fibrous cap thickness was smaller among females (96 ± 53 vs 112 ± 72 µm, p = 0.025), with more lesions harboring a thin cap fibroatheroma (39.3 % vs 24.9 %, p < 0.001). Major adverse cardiovascular events at two years occurred in 6.3 % of female patients and 11.8 % of male patients (p = 0.15). CONCLUSIONS: FFR-negative NC lesions after MI harbored more high-risk plaque features in female patients. Although this did not translate into an excess of recurrent events in female patients in this modestly sized cohort, it remains to be investigated whether this difference affects clinical outcome.

Angio-computed tomography reveals differences in the anatomy of renal arteries in resistant hypertension patients qualified for renal denervation versus pseudo-resistant hypertensive subjects.

BACKGROUND: Renal denervation is a novel therapeutic option in resistant hypertension (RHT). The anatomy of renal arteries and the presence of additional renal arteries are important determinants of the effect of the procedure. The aim of this study was to assess the anatomy of renal arteries using angio- -computed tomography in patients with RHT, who were qualified for renal denervation. METHODS: We analyzed angio-computed tomography scans of the renal arteries of 72 patients qualified for renal denervation. We divided the study population into two groups: a resistant hypertension group (RHT) and a pseudo-resistant hypertension group (NRHT). The biochemical and endocrine diagnostic procedures were performed to rule out secondary hypertension. We analyzed the morphology, the diameters, and the number of additional renal arteries. RESULTS: In both groups, we found additional renal arteries (ARN). ARN were more frequent in RHT than in patients with non-resistant hypertension (48.4% vs. 24.3%; p < 0.05). They were present more often on the left side (18 left side vs. 7 right side). The ARNs were longer than main renal artery - left side 41.7 ± 12.1 mm vs. 51.1 ± 11.8 mm, right side 49.2 ± 14.5 mm vs. 60 ± ± 8.6 mm, respectively (p < 0.05). The diameters of ARN were similar in both groups. In the group of patients with RHT the number of ARN was significantly higher (p < 0.04). CONCLUSIONS: The ARNs occur more often in patients with RHT. It seems that there is no connection between the resistance of hypertension and the diameters of renal arteries.