ABSTRACT
ß3-Adrenergic receptor expression is enhanced in the failing heart, but its functional effects are unclear. We tested the hypothesis that a ß3-agonist improves left ventricular (LV) performance in heart failure. We examined the chronic effects of a ß3-agonist in the angiotensin II (Ang II)-induced cardiomyopathy mouse model. C57BL/6J mice were treated with Ang II alone or Ang II + BRL 37344 (ß3-agonist, BRL) for 4 weeks. Systolic blood pressure in conscious mice was significantly elevated in Ang II and Ang II + BRL mice compared with control mice. Heart rate was not different among the three groups. Systolic performance parameters that were measured by echocardiography and an LV catheter were similar among the groups. LV end-diastolic pressure and end-diastolic pressure-volume relationships were higher in Ang II mice compared with control mice. However, the increase in these parameters was prevented in Ang II + BRL mice, which suggested improvement in myocardial stiffness by BRL. Pathologic analysis showed that LV hypertrophy was induced in Ang II mice and failed to be prevented by BRL. However, increased collagen I/III synthesis, cardiac fibrosis, and lung congestion observed in Ang II mice were inhibited by BRL treatment. The cardioprotective benefits of BRL were associated with downregulation of transforming growth factor-ß1 expression and phosphorylated-Smad2/3. Chronic infusion of a ß3-agonist has a beneficial effect on LV diastolic function independent of blood pressure in the Ang II-induced cardiomyopathy mouse model. SIGNIFICANCE STATEMENT: Chronic infusion of a ß3-adrenergic receptor agonist attenuates cardiac fibrosis and improves diastolic dysfunction independently of blood pressure in an angiotensin II-induced hypertensive mouse model. This drug might be an effective treatment of heart failure with preserved ejection fraction.
Subject(s)
Adrenergic beta-3 Receptor Agonists/pharmacology , Angiotensin II/pharmacology , Cardiomyopathies/physiopathology , Diastole/drug effects , Receptors, Adrenergic, beta-3/metabolism , Animals , Blood Pressure/drug effects , Cardiomyopathies/chemically induced , Cardiomyopathies/pathology , Disease Models, Animal , Echocardiography , Heart Rate/drug effects , Male , Mice , Mice, Inbred C57BL , Ventricular Function, Left/drug effects , Ventricular Remodeling/drug effectsABSTRACT
BACKGROUND AND AIMS: Peripheral artery disease (PAD), intermittent claudication, and impaired mobility contribute to the loss of skeletal muscle. This study investigated the impact of endovascular treatment (EVT) in patients suffering from PAD above the knee and its relation to baseline glycemic control. METHODS AND RESULTS: Mid-thigh muscle volume was measured before EVT, 3 months after EVT and 6 months after EVT. Mid-thigh muscle volumes of ipsilateral PAD patients with ischemic and non-ischemic legs were compared. Correlations between total thigh muscle volume and clinical characteristics were analyzed using univariable and multivariable analysis. Overall, thigh muscle volume increased after EVT. The mid-thigh muscle volume was significantly lower in patients with ipsilateral lesions and in those with ischemic lower limbs. The thigh muscle volume of those with ischemic lower limbs increased after EVT. Baseline glycated hemoglobin was the only factor that was negatively correlated with changes in the muscle volume after EVT. Muscle volume significantly increased in normoglycemic HbA1c<6.5% (47 mmol/mol) patients. There was no significant alteration in the muscle volume of hyperglycemic HbA1c ≥ 6.5% patients. CONCLUSION: Ischemic muscle atrophy was ameliorated after EVT in normoglycemic patients. There is a need for a large-scale trial to investigate whether EVT can protect or delay skeletal muscle loss.
Subject(s)
Angioplasty, Balloon , Blood Glucose/metabolism , Ischemia/therapy , Muscular Atrophy/pathology , Peripheral Arterial Disease/therapy , Quadriceps Muscle/pathology , Aged , Angioplasty, Balloon/instrumentation , Biomarkers/blood , Female , Glycated Hemoglobin/metabolism , Humans , Ischemia/blood , Ischemia/complications , Ischemia/diagnosis , Male , Multidetector Computed Tomography , Muscular Atrophy/diagnostic imaging , Muscular Atrophy/etiology , Organ Size , Peripheral Arterial Disease/blood , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/diagnosis , Pilot Projects , Predictive Value of Tests , Prospective Studies , Quadriceps Muscle/diagnostic imaging , Stents , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Bifurcation PCI is associated with a lower rate of procedural success, especially in multivessel disease patients. We aimed to determine the impact of bifurcation treatment on 2-years clinical outcomes when a state-of-the-art PCI strategy (heart team decision-making using the SYNTAX score II, physiology guided coronary stenosis assessment, thin strut bioresorbable polymer drug-eluting stent, and intravascular ultrasound guidance) is followed. METHODS: Three-vessel disease patients enrolled in the SYNTAX II trial (n = 454) were categorized in patients with (a) ≥1 treated bifurcation (n = 126), and (b) without bifurcation (n = 281). The primary endpoint was the occurrence of major adverse cardio and cerebrovascular events (MACCE-a composite of all-cause death, stroke, any myocardial infarction, or any revascularization) at 2 years. Secondary endpoints were the occurrence of target lesion failure (TLF) defined as cardiac death, target-vessel myocardial infarction and ischemia-driven target lesion revascularization, and the individual components of the composite primary endpoint, as well as stent thrombosis. RESULTS: A total of 145 bifurcation were treated in 126 patients. At 2 years, MACCE occurred in 75/407 patients (20.7% for bifurcation versus 17.5% for nonbifurcation, hazard ratio [HR] of 1.28, CI95% 0.78-2.08, p = .32). TLF presented a trend toward higher occurrence in bifurcation (16.8% vs. 10.8%, HR 1.75, CI95% 0.99-3.09, p = .053). Definite stent thrombosis did not differ at 2-year between groups (0.8% for the bifurcation vs. 0.7% for the nonbifurcation, p = .92). CONCLUSION: Bifurcation treatment in patients with three-vessel disease undergoing state-of-the-art PCI had similar event rate of MACCE but was associated with a trend toward higher incidence of TLF compared with nonbifurcation lesions.
Subject(s)
Coronary Artery Disease/therapy , Percutaneous Coronary Intervention , Aged , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Decision Support Techniques , Drug-Eluting Stents , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The aim of this study was to investigate the impact of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for bifurcation lesions. METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing 1-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The primary endpoint was a composite of all-cause death or new Q-wave myocardial infarction (MI) at 2 years. RESULTS: Among the 15,845 patients included in this subgroup analysis, 2,498 patients (15.8%) underwent PCI for at least one bifurcation lesion. The incidence of the primary endpoint was similar between the bifurcation and nonbifurcation groups (4.7 vs. 4.0%, p = .083). The experimental treatment had no significant effect on the primary endpoint according to the presence/absence of a bifurcation lesion (bifurcation: hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.51-1.07; nonbifurcation: HR: 0.90, 95% CI: 0.76-1.07, p for interaction = .343), but was associated with significant reduction in definite or probable stent thrombosis (p for interaction = .022) and significant excess of stroke (p for interaction = .018) when compared with the reference treatment. CONCLUSIONS: After PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial.
Subject(s)
Dual Anti-Platelet Therapy , Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors/administration & dosage , Purinergic P2Y Receptor Antagonists/administration & dosage , Ticagrelor/administration & dosage , Aged , Drug Administration Schedule , Drug-Eluting Stents , Dual Anti-Platelet Therapy/adverse effects , Dual Anti-Platelet Therapy/mortality , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/mortality , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Purinergic P2Y Receptor Antagonists/adverse effects , Recurrence , Risk Factors , Ticagrelor/adverse effects , Time Factors , Treatment OutcomeABSTRACT
AIMS: To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011). CONCLUSION: Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.
Subject(s)
Acute Coronary Syndrome/therapy , Myocardial Infarction/mortality , Percutaneous Coronary Intervention/methods , Purinergic P2Y Receptor Antagonists/therapeutic use , Ticagrelor/therapeutic use , Aged , Aspirin/adverse effects , Aspirin/therapeutic use , Case-Control Studies , Cause of Death/trends , Drug Therapy, Combination , Drug-Eluting Stents/adverse effects , Female , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Male , Middle Aged , Myocardial Infarction/physiopathology , Myocardial Infarction/therapy , Myocardial Revascularization/adverse effects , Myocardial Revascularization/methods , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Prospective Studies , Purinergic P2Y Receptor Antagonists/adverse effects , Stroke/chemically induced , Stroke/epidemiology , Stroke/mortality , Ticagrelor/adverse effectsABSTRACT
BACKGROUND: Little is known about serial changes in lumen and device dimensions after bioresorbable scaffold implantation in a growing animal model. MethodsâandâResults: ABSORB (n=14) or bare metal stents (ICROS amg [Abbott Vascular, Santa Clara, CA, USA], Winsen-Luhe, Germany; n=15) were implanted in the coronary arteries of domestic swine (a hybrid of Finnish-Norwegian Landrace swine) weighing 30-35 kg. Angiography and optical coherence tomography (OCT) were performed immediately after implantation and repeated at 7 days, 1, 3, 6 and 12 months after the index procedure. One month after implantation, mean lumen area decreased relative to baseline in both groups (relative area change from baseline, -41.4±15.6% for ABSORB vs. -20.9±18.6% for ICROS) while mean device area decreased only in the ABSORB group (relative area change: -11.1±9.4% vs. +0.14±7.95%, respectively). At 12 months, mean lumen area increased relative to baseline in both groups (relative area change from baseline, +55.6±22.4% vs. +32.3±83.6%, respectively) in accordance with the swine growth weighing up to 260-300 kg. Mean device area in the ICROS group remained stable whereas that in the ABSORB group began to increase between 3 and 6 months along with the vessel growth (relative area change: +107.8±25.7% vs. +0.14±7.95%). CONCLUSIONS: In the growing porcine model, ABSORB was associated with greater extent of recoil 1 month after implantation compared with ICROS but demonstrated substantial adaptability to vessel growth in late phase.
Subject(s)
Absorbable Implants/standards , Coronary Vessels/diagnostic imaging , Stents/standards , Tomography, Optical Coherence/methods , Animals , Coronary Angiography/methods , Coronary Vessels/growth & development , Coronary Vessels/surgery , Models, Animal , Prosthesis Design/standards , Swine , Time FactorsABSTRACT
Contrast media are considered to cause acute kidney injury by activating various factors that induce renal vasoconstriction. We analysed the renal microvascular haemodynamic response using the Doppler flow wire method. Then changes in urinary liver-type fatty acid-binding protein levels following contrast medium administration were compared between groups with or without a micro-injury of the kidney. In the group without renal micro-injury, the average peak velocity (APV) decreased significantly, whereas the renal artery resistance index (RI) increased significantly following contrast medium administration. In contrast, there was no significant change in either the APV or RI in the group with a renal micro-injury. A blunted microvascular response was found in the micro-injury group, whereas microvascular resistance increased in the non-micro-injury group.
Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnostic imaging , Contrast Media/adverse effects , Vasoconstriction/drug effects , Aged , Aged, 80 and over , Coronary Angiography/adverse effects , Female , Humans , Kidney/blood supply , Kidney/diagnostic imaging , Kidney/drug effects , Male , Middle Aged , Vasoconstriction/physiologyABSTRACT
BACKGROUND: We investigated the influence of geographical predisposition on the spatial distribution and composition of coronary plaques. METHODS: Thirty coronary arteries were evaluated. A total of 1441 cross-sections were collected from intravascular ultrasound (IVUS) and radio-frequency signal-based virtual histology (VH-IVUS) imaging. To exclude complex geographical effects of side branches and to localise the plaque distribution, we analysed only eccentric plaques in non-branching regions. The spatial distribution of eccentric plaques in the coronary artery was classified into myocardial, lateral, and epicardial regions. The composition of eccentric plaques was analysed using VH-IVUS. RESULTS: The plaque was concentric in 723 sections (50.2%) and eccentric in 718 (49.9%). Eccentric plaques were more frequently distributed towards the myocardial side than towards the epicardial side (46.7 ± 7.5% vs. 12.5 ± 4.2%, p = 0.003). No significant difference was observed between the myocardial and lateral sides (46.7 ± 7.5% vs. 20.8 ± 5.0%) or between the lateral and epicardial sides. Eccentric thin-capped fibroatheromas were more frequently distributed towards the myocardial side than towards the lateral side (p = 0.024) or epicardial side (p = 0.005). CONCLUSION: Geographical predisposition is associated with distribution, tissue characterisation, and vulnerability of plaques in non-branching coronary arteries.
Subject(s)
Coronary Artery Disease/diagnosis , Coronary Vessels/diagnostic imaging , Plaque, Atherosclerotic/diagnosis , Ultrasonography, Interventional/methods , Aged , Coronary Angiography , Coronary Artery Disease/physiopathology , Coronary Vessels/physiopathology , Cross-Sectional Studies , Female , Humans , Male , Plaque, Atherosclerotic/physiopathology , Severity of Illness IndexABSTRACT
Contrast-induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty-six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m(2) (CKD and non-CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = -0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non-CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non-CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media.
Subject(s)
Contrast Media/adverse effects , Contrast Media/chemistry , Iodine/chemistry , Kidney/drug effects , Kidney/physiology , Microvessels/drug effects , Vascular Resistance/drug effects , Aged , Biomarkers/metabolism , Cardiac Catheterization , Female , Humans , Kidney/metabolism , Kidney/physiopathology , Male , Microvessels/physiology , Microvessels/physiopathology , Middle Aged , Renal Artery/drug effects , Renal Artery/physiology , Renal Artery/physiopathology , Renal Circulation/drug effects , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/therapyABSTRACT
Mast cells are widely distributed in the body and affect their surrounding environment through degranulation and secretion of cytokines. Conversely, mast cells are influenced by environmental stimuli such as cyclical mechanical stretch (CMS), such as that induced by heartbeat and respiration. Peripherally distributed mast cells are surrounded by extracellular matrix, where they bind IgE on their surface by expressing the high-affinity Fc receptor for IgE (FcεRI), and they release mediators after cross-linking of surface-bound IgE by allergen. To analyse how CMS affects mast cell responses, we examined the effect of applying CMS on the behaviour of IgE-bound mast cells (RBL-2H3 cell line) adhering to fibronectin as a substitute for extracellular matrix. We found that CMS enhanced FcεRI-mediated secretion in the presence of antigen (2,4-dinitrophenol-bovine serum albumin). CMS increased expression of IL-4 mRNA and secretion of IL-4 protein. Western blot analysis showed that CMS changes the signal transduction in mitogen-activated protein kinases and AKT, which in turn alters the regulation of IL-4 and increases the secretion of IL-4. These results suggest that CMS modulates the effect of mast cells on inflammation and resultant tissue remodelling. Understanding how CMS affects mast cell responses is crucial for developing therapies to treat mast cell-related diseases.
Subject(s)
Cell Degranulation , Interleukin-4/metabolism , Mast Cells/physiology , Stress, Mechanical , Animals , Cell Adhesion , Cell Line , Fibronectins/physiology , Immunoglobulin E/metabolism , Interleukin-4/genetics , Mast Cells/immunology , Rats , Receptors, IgE/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , beta-N-Acetylhexosaminidases/metabolismABSTRACT
Peripheral artery disease (PAD) compromises walking and physical activity, which results in further loss of skeletal muscle. The cross-sectional area of the thigh muscle has been shown to be correlated with systemic skeletal muscle volume. In our previous pilot study, we observed an increase in thigh muscle mass following endovascular treatment (EVT) in patients with proximal vascular lesions affecting the aortoiliac and femoropopliteal arteries. Considering the potential interactions between skeletal muscle, lipid profile, and glucose metabolism, we aimed to investigate the relationship between thigh muscle mass and apolipoproteins as well as glucose metabolism in PAD patients undergoing EVT. This study is a prespecified sub-study conducted as part of a pilot study. We prospectively enrolled 22 symptomatic patients with peripheral artery disease (PAD) and above-the-knee lesions, specifically involving the blood vessels supplying the thigh muscle. The mid-thigh muscle area was measured with computed tomography before and 6 months after undergoing EVT. Concurrently, we measured levels of apolipoproteins A1 (Apo A1) and B (Apo B), fasting blood glucose, 2 h post-load blood glucose (using a 75 g oral glucose tolerance test), and glycated hemoglobin A1c (HbA1c). Changes in thigh muscle area (delta muscle area: 2.5 ± 8.1 cm2) did not show significant correlations with changes in Apo A1, Apo B, fasting glucose, 2 h post-oral glucose tolerance test blood glucose, HbA1c, or Rutherford classification. However, among patients who experienced an increase in thigh muscle area following EVT (delta muscle area: 8.41 ± 5.93 cm2), there was a significant increase in Apo A1 (pre: 121.8 ± 15.1 mg/dL, 6 months: 136.5 ± 19.5 mg/dL, p < 0.001), while Apo B remained unchanged (pre: 76.4 ± 19.2 mg/dL, 6 months: 80.5 ± 4.9 mg/dL). Additionally, post-oral glucose tolerance test 2 h blood glucose levels showed a decrease (pre: 189.7 ± 67.5 mg/dL, 6 months: 170.6 ± 69.7 mg/dL, p = 0.075). Patients who exhibited an increase in thigh muscle area demonstrated more favorable metabolic changes compared to those with a decrease in thigh muscle area (delta muscle area: -4.67 ± 2.41 cm2). This pilot sub-study provides insights into the effects of EVT on thigh muscle, apolipoproteins, and glucose metabolism in patients with PAD and above-the-knee lesions. Further studies are warranted to validate these findings and establish their clinical significance. The trial was registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN000047534).
ABSTRACT
Background and Aims: As the population of aging societies continues to grow, the prevalence of complex coronary artery diseases, including calcification, is expected to increase. Rotational atherectomy (RA) is an essential technique for treating calcified lesions. This study aimed to assess the usefulness of the drilling noise produced during rotablation as a parameter for evaluating the safety and effectiveness of the procedure. Methods: A human body model mimicking calcified stenotic coronary lesions was constructed using plastic resin, and burrs of sizes 1.25 and 1.5 mm were utilized. To identify the noise source during rotablation, we activated the ROTAPRO™ rotablator at a rotational speed of 180,000 rpm, recording the noise near the burr (inside the mock model) and advancer (outside). In addition to regular operation, we simulated two major complications: burr entrapment and guidewire transection. The drilling noise recorded in Waveform Audio File Format files was converted into spectrograms for analysis and an autoencoder analyzed the image data for anomalies. Results: The drilling noise from both inside and outside the mock model was predominantly within the 3000 Hz frequency domain. During standard operation, intermittent noise within this range was observed. However, during simulated complications, there were noticeable changes: a drop to 2000 Hz during burr entrapment and a distinct squealing noise during guidewire transection. The autoencoder effectively reduced the spectrogram data into a two-dimensional representation suitable for anomaly detection in potential clinical applications. Conclusion: By analyzing drilling noise, the evaluation of procedural safety and efficacy during RA can be enhanced.
ABSTRACT
BACKGROUND: Chronic total occlusion (CTO) is a high-risk factor for stent thrombosis, but little is known about the difference in neointimal healing between CTO and non-CTO lesions regarding implanted stents. We investigated factors affecting neointimal healing after stent implantation for CTO and non-CTO lesions using angioscopy. METHODS: We retrospectively evaluated 106 stents in 85 consecutive patients between March 2016 and July 2020. Their average age was 68⯱â¯11â¯years, and participants (73 male and 12 female) underwent follow-up angiography and angioscopy 1â¯year after percutaneous coronary intervention (PCI). The stents (nâ¯=â¯106) were divided into three groups according to the lesion status at the previous PCI: CTO (nâ¯=â¯17), acute coronary syndrome (ACS) (nâ¯=â¯35), and stable coronary artery disease without CTO or non-CTO (nâ¯=â¯54). RESULTS: The neointimal stent coverage grade was significantly lower in the CTO and ACS groups than in the non-CTO group (0.4⯱â¯0.5, 0.9⯱â¯0.8, and 1.4⯱â¯0.8, respectively, pâ¯<â¯0.001). Thrombi were significantly more frequent in CTO and ACS than in non-CTO (71â¯%, 51â¯%, and 15â¯%, respectively, pâ¯<â¯0.001). The yellow grade in CTO was comparable to that in ACS but significantly higher in CTO than in non-CTO (CTO vs. ACS vs. non-CTO 1.5⯱â¯0.7, 1.4⯱â¯0.6, and 0.9⯱â¯0.7, respectively, pâ¯=â¯0.007). CONCLUSIONS: Delayed healing occurs in stents implanted for CTO lesions. Longer dual-antithrombotic therapy may be beneficial.
Subject(s)
Coronary Occlusion , Coronary Thrombosis , Percutaneous Coronary Intervention , Humans , Male , Female , Middle Aged , Aged , Percutaneous Coronary Intervention/adverse effects , Angioscopy , Coronary Thrombosis/pathology , Retrospective Studies , Coronary Angiography/adverse effects , Neointima , Treatment Outcome , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/therapy , Chronic DiseaseABSTRACT
Vascular Ehlers-Danlos syndrome (vEDS) causes fatal vascular complications due to vascular fragility. However, invasive therapeutic procedures are generally avoided except in emergencies. We report a case of vEDS presenting with rapid expansion of a hepatic arterial aneurysm successfully treated using prophylactic endovascular therapy. A 43-year-old woman with vEDS confirmed by genetic testing was hospitalized for a symptomatic hepatic arterial aneurysm that expanded rapidly within a week. Prophylactic coil embolization was then successfully performed. Although the general applicability of this approach cannot be determined, prophylactic endovascular therapy can clearly be an option for arterial aneurysms at high risk of rupture.
ABSTRACT
AIMS: To investigate the variability between site and core laboratory (CL) calculation of the anatomical SYNTAX score (SS) based on coronary computed tomography angiography (CTA) alone and functional SS based on coronary CTA and fractional flow reserve derived from computed tomography (FFRCT) in the SYNTAX III trial. METHODS AND RESULTS: The SYNTAX III trial was a multicentre, international study that included 223 patients with three-vessel disease with or without left main involvement. Functional SS was computed by subtracting non-flow limiting stenoses (FFRCT > 0.80) from anatomical SS. SS was combined with clinical information to generate the SYNTAX score II (SS II) that provides treatment recommendations. The mean anatomical SS based on coronary CTA alone was 33.4 ± 12.7 by sites and 37.1 ± 13.4 by CL (P < 0.001). The mean functional SS based on coronary CTA and FFRCT was 30.5 ± 13.0 by sites and 33.3 ± 13.6 by CL (P < 0.001). The intraclass correlation coefficient was 0.49 [95% confidence interval (CI) 0.37-0.59) in anatomical SS and 0.62 (95% CI 0.52-0.70) in functional SS. The Cohen's κ comparing treatment recommendation between sites and CL was 0.68 (95% CI 0.58-0.78) based on anatomical SS and 0.71 (95% CI 0.60-0.82) based on functional SS. CONCLUSION: The mean anatomical SS derived from coronary CTA alone and functional SS based on coronary CTA and FFRCT were higher when assessed by the CL than by the sites themselves. However, substantial agreement in treatment recommendation by SS II between sites and CL was demonstrated. CLINICAL TRIALS.GOV IDENTIFIER: NCT02385279.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/surgery , Coronary Vessels/diagnostic imaging , Humans , Laboratories , Predictive Value of TestsABSTRACT
Importance: Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI). Objectives: To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies. Design, Setting, and Participants: This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15â¯991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019. Interventions: Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy. Main Outcomes and Measures: The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding. Results: Of the 15â¯968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045). Conclusions and Relevance: Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years. Trial Registration: ClinicalTrials.gov identifier: NCT01813435.
Subject(s)
Coronary Artery Disease/therapy , Hemorrhage/epidemiology , Hemorrhagic Stroke/epidemiology , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Aged , Aspirin/therapeutic use , Drug-Eluting Stents , Dual Anti-Platelet Therapy/adverse effects , Dual Anti-Platelet Therapy/methods , Female , Hemorrhage/chemically induced , Hemorrhagic Stroke/chemically induced , Humans , Ischemic Stroke/epidemiology , Male , Middle Aged , Mortality , Myocardial Infarction/epidemiology , Myocardial Revascularization/statistics & numerical data , Proportional Hazards Models , Secondary Prevention , Sex Factors , Thrombosis/epidemiology , Ticagrelor/therapeutic useABSTRACT
OBJECTIVES: The aim of this study was to investigate the impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) on clinical outcomes in patients with de novo 3-vessel disease (3VD) treated with contemporary PCI. BACKGROUND: The clinical impact of post-PCI QFR in patients treated with state-of-the-art PCI for de novo 3VD is undetermined. METHODS: All vessels treated in the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) II trial were retrospectively screened and analyzed for post-PCI QFR. The primary endpoint of this substudy was vessel-oriented composite endpoint (VOCE) at 2 years, defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction, and target vessel revascularization. The receiver-operating characteristic curve was used to calculate the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE. All the analyzable vessels were stratified on the basis of the optimal cutoff value. RESULTS: A total of 968 vessels treated with PCI were screened. Post-PCI QFR was analyzable in 771 (79.6%) vessels. A total of 52 (6.7%) VOCEs occurred at 2 years. The mean value of post-PCI QFR was 0.91 ± 0.07. The diagnostic performance of post-PCI QFR to predict 2-year VOCE was moderate (area under the curve: 0.702; 95% confidence interval: 0.633 to 0.772), with the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE 0.91 (sensitivity 0.652, specificity 0.635). The incidence of 2-year VOCE in the vessels with post-PCI QFR <0.91 (n = 284) was significantly higher compared with vessels with post-PCI QFR ≥0.91 (n = 487) (12.0% vs. 3.7%; hazard ratio: 3.37; 95% confidence interval: 1.91 to 5.97; p < 0.001). CONCLUSIONS: A higher post-PCI QFR value is associated with improved vessel-related clinical outcomes in state-of-the art PCI practice for de novo 3VD. Achieving a post-PCI QFR value ≥0.91 in all treated vessels should be a target when treating de novo 3VD. These findings require confirmation in future prospective trials.
Subject(s)
Coronary Artery Disease/therapy , Coronary Vessels/physiopathology , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Aged , Clinical Trials as Topic , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Artery Disease/physiopathology , Coronary Vessels/diagnostic imaging , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Predictive Value of Tests , Retrospective Studies , Risk Factors , Stents , Time Factors , Treatment OutcomeABSTRACT
Q-wave myocardial infarction (QWMI) comprises 2 entities. First, a clinically evident MI, which can occur spontaneously or be related to a coronary procedure. Second, silent MI which is incidentally detected on serial electrocardiographic (ECG) assessment. The prevalence of silent MI after percutaneous coronary intervention (PCI) in the drug-eluting stent era has not been fully investigated. The GLOBAL LEADERS is an all-comers multicenter trial which randomized 15,991 patients who underwent PCI to 2 antiplatelet treatment strategies. The primary end point was a composite of all-cause death or nonfatal new QWMI at 2-years follow-up. ECGs were collected at discharge, 3-month and 2-year visits, and analyzed by an independent ECG core laboratory following the Minnesota code. All new QWMI were further reviewed by a blinded independent cardiologist to identify a potential clinical correlate by reviewing clinical information. Of 15,968 participants, ECG information was complete in 14,829 (92.9%) at 2 years. A new QWMI was confirmed in 186 (1.16%) patients. Transient new Q-waves were observed in 28.5% (53 of 186) of them during the follow-up. The majority of new QWMI (78%, 146 of 186) were classified as silent MI due to the absence of a clinical correlate. Silent MI accounted for 22.1% (146 of 660) of all MI events. The prevalence of silent MI did not differ significantly between treatment strategies (experimental vs reference: 0.88% vs 0.98%, pâ¯=â¯0.5027). In conclusion, we document the prevalence of silent MI in an all-comers population undergoing PCI in this large-scale randomized trial.
Subject(s)
Aspirin/therapeutic use , Asymptomatic Diseases/mortality , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/methods , Ticagrelor/therapeutic use , Aged , Analysis of Variance , Coronary Angiography/methods , Drug Therapy, Combination , Drug-Eluting Stents , Electrocardiography/methods , Female , Humans , Internationality , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Percutaneous Coronary Intervention/mortality , Prognosis , Prospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Treatment OutcomeABSTRACT
Aims: Coronary angioscopy (CAS) is a robust imaging methodology for evaluation of vascular healing response after stenting. However, the procedure requires a guiding catheter with a diameter of more than 6 Fr, which is rather invasive at follow-up angiography. Recently, coronary angioscopes of a smaller diameter have been able to pass through a 4 Fr guiding catheter. This study aimed to investigate the feasibility and safety of slender CAS observation using a 4 Fr guiding catheter. Methods and results: Thirty-three consecutive patients who underwent follow-up angiography were evaluated. Following usual angiography via the radial artery, the stent segment was observed by non-occlusive CAS through a 4 Fr guiding catheter. Low molecular weight dextran-L (4 mL/sec) was flushed from a guiding catheter to replace coronary blood. The success rate, anatomical or procedural factors related to the success, and incidence of adverse events were examined. The success rate was 84.8% (n=28/33). The luminal diameter at the orifice of the target vessel was larger in the successful than in the failed group (4.03±0.61 mm vs. 3.39±0.61 mm, respectively; p=0.009). The presence of deep engagement of the guiding catheter into the target vessel was a key factor for sufficient observation (100% in the successful group vs. 0% in the failed group; p<0.0001). No adverse events, such as dissection or acute coronary syndrome, were reported. Conclusions: The new method of CAS through a 4 Fr guiding catheter demonstrated high feasibility and safety. This less invasive observation via CAS may be useful for stent follow-up.