OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Effects of exenatide on coronary stent's endothelialization in subjects with type 2 diabetes: a randomized controlled trial. The Rebuild study.

BACKGROUND: Subjects with type 2 diabetes (T2D) have a higher risk of in-stent restenosis and stent thrombosis. The activation of the glucagon-like peptide-1 receptor (GLP-1R) has been suggested to induce several effects on the vasculature that may reduce the risk of stent failure following an angioplasty. The aim of this study is to evaluate the effect of the GLP-1R agonist exenatide on endothelialization of a modern drug-eluting stent (DES) in subjects with T2D. METHODS: 38 subjects with T2D who were eligible for revascularization with implantation of DES were randomized to treatment with exenatide (once weekly) plus standard treatment, or to standard treatment alone. After 12 weeks, a new coronary angiography was performed to evaluate the percentage of strut coverage (primary endpoint) and the presence of neo-atherosclerosis by optical coherence tomography. This study was approved by the Stockholm's Ethical Review Board. RESULTS: The two groups were well balanced regarding baseline clinical characteristics. Strut coverage was 95% (88.7-98.5%) in the exenatide group and 91.4% (88.8-98.5%) in the control group (p = 0.692). There were no significant differences between groups neither in the thickness of neo-intima (0.2 mm in both groups, p = 0.471), nor the maximal in-stent obstruction by neo-intima (15.5% in exenatide group vs 14.7% in control group, p = 0.801). No significant differences were detected in the rate of target lesion revascularization between groups (p = 0.224). CONCLUSION: Twelve weeks treatment with exenatide did not lead to a significantly better stent coverage in people with T2D. No significant differences in the occurrence of neo-atherosclerosis were detected between groups. TRIAL REGISTRATION: The study was registered at www. CLINICALTRIALS: gov (Rebuild Study, NCT02621489).

Index of Microcirculatory Resistance Measured during Intracoronary Adenosine-Induced Hyperemia.

BACKGROUND: The index of microcirculatory resistance is an invasive measure of coronary microvascular function that has to be calculated during maximal hyperemia, classically achieved with intravenous adenosine (IV). The aim of this study was to evaluate the use of intracoronary (IC) adenosine for the calculation of IMR. METHODS AND RESULTS: 31 patients with stable coronary artery disease were included in the study. Coronary pressure and thermodilution measurements were obtained at rest and during maximal hyperemia using a pressure-temperature sensor-tipped coronary guidewire. Duplicate measurements were performed using first IC and then IV adenosine. Dispersion of transit times was comparable for IC and IV adenosine. IMR values based on IC vs IV adenosine showed a high level of agreement and an intraclass correlation coefficient of 0.90. Applying an upper normal limit of 25, misclassification of IMR using IC adenosine was seen in just one patient in whom IC adenosine resulted in a lower value. A simplified procedure based on a single bolus dose of saline did not change the level of agreement or the rate of misclassification. CONCLUSIONS: We found an excellent agreement between IMR values measured during hyperemia induced by IC as compared to IV adenosine. The use of IC adenosine may facilitate invasive assessment of microvascular function and is potentially time- and cost-saving with less patient discomfort as compared to IV infusion. The trail is registered with NCT03369184.

Rational and design of the European randomized Optical Coherence Tomography Optimized Bifurcation Event Reduction Trial (OCTOBER).

Background: Percutaneous coronary intervention in complex bifurcation lesions is prone to suboptimal implantation results and is associated with increased risk of subsequent clinical events. Angiographic ambiguity is high during bifurcation stenting, but it is unknown if procedural guidance by intravascular optical coherence tomography (OCT) improves clinical outcome. Methods and Design: OCTOBER is a randomized, investigator-initiated, multicenter trial aimed to show superiority of OCT-guided stent implantation compared to standard angiographic-guided implantation in bifurcation lesions. The primary outcome measure is a 2-year composite end point of cardiac death, target lesion myocardial infarction, and ischemia-driven target lesion revascularization. The calculated sample size is 1,200 patients in total, and allocation is 1:1. Eligible patients have stable or unstable angina pectoris or stabilized non­ST elevation myocardial infarction, and a coronary bifurcation lesion with significant main vessel stenosis and more than 50 % stenosis in a side branch with a reference diameter ≥2.5mm. Treatment is performed by the provisional side branch stenting technique or 2-stent techniques, and the systematic OCT guiding protocol is aimed to evaluate (1) plaque preparation, (2) lesion length, (3) segmental reference sizes, (4) lesion coverage, (5) stent expansion, (6) malapposition, (7) wire positions, and (8) ostial results. Implications: A positive outcome of the OCTOBER trial may establish OCT as a routine tool for optimization of complex percutaneous coronary intervention, whereas a negative result would indicate that OCT remains a tool for ad hoc evaluation in selected cases.

Glycemic Control and Coronary Stent Failure in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: The impact of glycemic control in the risk of stent failure in subjects with type 2 diabetes (T2D) is currently unknown. OBJECTIVES: This study sought to study whether poor glycemic control is associated with a higher risk of stent failure in subjects with T2D. METHODS: This observational study included all patients in Sweden with T2D who underwent implantation of second-generation drug-eluting stents (DES) during 2010 to 2020. The exposure variable was the updated mean of glycated hemoglobin (HbA1c). Individuals were stratified by glycemic control, with HbA1c 6.1% to 7.0% (43-53 mmol/mol) as the reference group. The primary endpoint was the occurrence of stent failure (in-stent restenosis and stent thrombosis). The main result was analyzed in a complete cases model. Sensitivity analyses were performed for missing data and a model with death as a competing risk. RESULTS: The study population consisted of 52,457 individuals (70,453 DES). The number of complete cases was 24,411 (29,029 DES). The median follow-up was 6.4 years. The fully adjusted HR was 1.10 (95% CI: 0.80-1.52) for HbA1c of ≤5.5% (≤37 mmol/mol), 1.02 (95% CI: 0.85-1.23) for HbA1c of 5.6% to 6.0% (38-42 mmol/mol), 1.25 (95% CI: 1.11-1.41) for HbA1c of 7.1% to 8.0% (54-64 mmol/mol), 1.30 (95% CI: 1.13-1.51) for HbA1c of 8.1% to 9.0% (65-75 mmol/mol), 1.46 (95% CI: 1.21-1.76) for HbA1c of 9.1% to 10.0% (76-86 mmol/mol), and 1.33 (95% CI: 1.06-1.66) for HbA1c of ≥10.1% (≥87 mmol/mol). Sensitivity analyses did not change the main result. CONCLUSIONS: We found a significant association between poor glycemic control and a higher risk of stent failure driven by in-stent restenosis.

Risk of stent failure in patients with diabetes treated with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors: A nationwide observational study.

BACKGROUND: Incretins are a group of glucose-lowering drugs with favourable cardiovascular (CV) effects against neoatherosclerosis. Incretins' potential effect in stent failure is unknown. The aim of this study is to determine if incretin treatment decreases the risk of stent-thrombosis (ST), and/or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with implanted drug-eluting stents (DES). METHODS: Observational study including all diabetes patients who underwent PCI with DES in Sweden from 2007 to 2017. By merging 5 national registers, the information on patient characteristics, outcomes and drug dispenses was retrieved. Cox regression analysis with estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) was used to analyse for the occurrence of ST/ISR, and major adverse cardiovascular events (MACE). A subgroup analysis for the type of incretin treatment was performed. RESULTS: In total 18,505 diabetes patients (30% women) underwent PCI, and 32,463 DES were implanted. Of those, 10% (3449 DES in 1943 patients) were treated with incretins. Median follow-up time was 995 days (Control Group) vs. 771 days (Incretin Group). No significant difference in the risk of ST/ISR was found neither for the main study group (HR:0.98 95% CI:0.80-1.19) nor for the subgroups. No reduction of the risk of MACE (HR:0.96 95% CI:0.88-1.06) was observed. There was a 26% lower risk for CV death in favour of incretin treated patients (HR:0.74 95% CI:0.57-0.95). CONCLUSION: In diabetes patients who underwent PCI incretin treatment was not associated with lower risk of stent failure, but with lower risk of CV death.

Heart rate variability in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment, both in combination with metformin: A randomized, open, parallel-group study.

AIMS: Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV. METHODS: This was a post hoc study whereas sixty-two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat-to-beat (NN) intervals (SDNN), was assessed by 24-hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF), low-frequency (LF) and very low-frequency power. RESULTS: Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide-treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis. CONCLUSIONS: Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.

The MOVEMENT Trial.

Background Morphine administration is a strong predictor of delayed onset of action of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction, likely because of impaired gastrointestinal motility. The aim of this study was to evaluate whether the peripheral opioid antagonist methylnaltrexone could improve pharmacodynamics and pharmacokinetics of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Methods and Results The MOVEMENT (Methylnaltrexone to Improve Platelet Inhibition of Ticagrelor in Morphine-Treated Patients With ST-Segment Elevation Myocardial Infarction) trial was a multicenter, prospective, randomized, controlled trial in patients with ST-segment-elevation myocardial infarction treated with morphine and ticagrelor. Upon arrival to the catheterization laboratory, patients were randomized to a blinded intravenous injection of either methylnaltrexone (8 or 12 mg according to weight) or 0.9% sodium chloride. The proportion of patients with high on-treatment platelet reactivity and plasma concentrations of ticagrelor and AR -C124910XX were assessed at baseline (arrival in the catheterization laboratory) and 1 and 2 hours later. A total of 82 patients received either methylnaltrexone (n=43) or placebo (n=39). Median (interquartile range) time from ticagrelor administration to randomization was 41 (31-50) versus 45.5 (37-60) minutes ( P=0.16). Intravenous methylnaltrexone administration did not significantly affect prevalence of high on-treatment platelet reactivity at 2 hours after inclusion, the primary end point, when compared with placebo (54% versus 51%, P=0.84). Plasma concentrations of ticagrelor and its active metabolite, the prespecified secondary end points, did not differ significantly between the groups over time. There was no significant difference in patient self-estimated pain between the groups. Conclusions Methylnaltrexone did not significantly improve platelet reactivity or plasma concentrations of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02942550.

Effects on repetitive 24-hour ambulatory blood pressure in subjects with type II diabetes randomized to liraglutide or glimepiride treatment both in combination with metformin: a randomized open parallel-group study.

In this post hoc study, we aimed to investigate liraglutide treatment on repetitive 24-hour blood pressure (BP) in patients with type II diabetes. Sixty-two individuals with type II diabetes (45 males) were randomized to 1.8 mg liraglutide once daily or 4 mg glimepiride together with 1 g metformin twice daily. Ambulatory 24-hour systolic and diastolic blood pressure (sBP/dBP) was repetitively measured at baseline, 2 weeks, and 18 weeks. Outcomes were evaluated as treatment change from baseline, 2 weeks, and 18 weeks. Baseline clinical characteristics of liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. No statistically significant difference in 24-hour sBP/dBP between three time periods and groups was observed. There was no treatment change for 24-hour sBP at week 2 or after week 18. There was a transient treatment change in 24-hour dBP in the liraglutide group at week 2 (3.2 ± 5.4 vs. -1.2 ± 4.5 mm Hg, P < .01). A treatment change in 24-hour heart rate at week 2 (4.9 ± 6.8 vs. 1.0 ± 6.0 bpm, P = .03) and at week 18 (5.9 ± 7.8 vs. 0.2 ± 6.3 bpm, P < .01) was observed in the liraglutide group. In conclusion, liraglutide treatment did not lower BP. However, a small diurnal variation in dBP without affecting BP variability or nocturnal BP dipping was observed.

Corrigendum: Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open Parallel-Group Study.

[This corrects the article on p. 325 in vol. 8, PMID: 29184539.].

Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open Parallel-Group Study.

Objective: We aimed to investigate the effect of liraglutide treatment on heart function in type 2 diabetes (T2D) patients with subclinical heart failure. Methods: Randomized open parallel-group trial. 62 T2D patients (45 male) with subclinical heart failure were randomized to either once daily liraglutide 1.8 mg, or glimepiride 4 mg, both add on to metformin 1 g twice a day. Mitral annular systolic (s') and early diastolic (e') velocities were measured at rest and during bicycle ergometer exercise, using tissue Doppler echocardiography. The primary endpoint was 18-week treatment changes in longitudinal functional reserve index (LFRIdiastolic/systolic). Results: Clinical characteristics between groups (liraglutide = 33 vs. glimepiride = 29) were well matched. At baseline left ventricle ejection fraction (53.7 vs. 53.6%) and global longitudinal strain (-15.3 vs. -16.5%) did not differ between groups. There were no significant differences in mitral flow velocities between groups. For the primary endpoint, there was no treatment change [95% confidence interval] for: LFRIdiastolic (-0.18 vs. -0.53 [-0.28, 2.59; p = 0.19]), or LFRIsystolic (-0.10 vs. -0.18 [-1.0, 1.7; p = 0.54]); for the secondary endpoints, there was a significant treatment change in respect of body weight (-3.7 vs. -0.2 kg [-5.5, -1.4; p = 0.001]), waist circumference (-3.1 vs. -0.8 cm [-4.2, -0.4; p = 0.019]), and heart rate (HR) (6.3 vs. -2.3 bpm [-3.0, 14.2; p = 0.003]), with no such treatment change in hemoglobin A1c levels (-11.0 vs. -9.2 mmol/mol [-7.0, 2.6; p = 0.37]), between groups. Conclusion: 18-week treatment of liraglutide compared with glimepiride did not improve LFRIdiastolic/systolic, but however increased HR. There was a significant treatment change in body weight reduction in favor for liraglutide treatment.

Anti-Ro/SSA antibodies and cardiac rhythm disturbances: Present and future perspectives.

Several case reports, small case series, and original research papers have recently suggested that the action of certain auto-antibodies related to connective tissue diseases may be responsible for significant cardiac rhythm disturbances in adults. The relationship between anti-Ro/SSA antibodies and congenital complete atrioventricular block is well recognized in the fetal heart. Herein we review the emerging evidences of the link to increased levels of anti-Ro/SSA antibodies with rhythm disorders of unknown origin in the adult. Confirmation of this distinct etiology may eventually be the basis for new therapies.