Treatment of elderly patients with non-ST-elevation myocardial infarction: the nationwide POPular age registry.

OBJECTIVE: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry. METHODS: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician. Cardiovascular events consisted of cardiovascular death, myocardial infarction and ischaemic stroke. Bleeding was classified according to the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 646 patients were enrolled between August 2016 and May 2018. Median age was 81 (IQR 77-84) years and 58% were male. Overall, 75% underwent coronary angiography, 40% percutaneous coronary intervention, and 11% coronary artery bypass grafting, while 49.8% received pharmacological therapy only. At discharge, dual antiplatelet therapy (aspirin and P2Y12 inhibitor) was prescribed to 56.7%, and 27.4% received oral anticoagulation plus at least one antiplatelet agent. At 1­year follow-up, cardiovascular death, myocardial infarction or stroke had occurred in 13.6% and major bleeding (BARC 3 and 5) in 3.9% of patients. The risk of both cardiovascular events and major bleeding was highest during the 1st month. However, cardiovascular risk was three times as high as bleeding risk in this elderly population, both after 1 month and after 1 year. CONCLUSIONS: In this national registry of elderly patients with NSTEMI, the majority are treated according to current European Society of Cardiology guidelines. Both the cardiovascular and bleeding risk are highest during the 1st month after NSTEMI. However, the cardiovascular risk was three times as high as the bleeding risk.

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.

Dutch multicenter experience using the STENTYS Xposition S self-apposing stent in complex coronary lesions.

OBJECTIVES: The aim is to assess the experience in the Netherlands using the Xposition S self-apposing stent in complex coronary lesions in clinical practice. BACKGROUND: Treatment of complex coronary lesions could be accompanied with stent sizing difficulties and complications, particularly due to vessel overdilation or stent underexpansion. The self-apposing feature of the Xposition S stent (STENTYS, Paris, France) supports good strut apposition in complex anatomies and allows for an increase in diameter after implantation. METHODS: In this real-world registry, data from patients treated with Xposition S in four Dutch clinical sites were prospectively collected and analyzed. Any patient suitable for implantation with Xposition S according to current recommendations was enrolled. Primary endpoint was major adverse cardiac events (MACE) at 1 year. RESULTS: Between 2015 and 2018, data from 251 patients were collected. Clinical presentation was an acute coronary syndrome in majority of the patients (76.9%). Main angiographic indications were lesions in aneurysmatic or ectatic vessels (32.3%), thrombus containing lesions (13.1%), and bifurcation/left main stenosis (10.4%). Most of the target lesions (TLs) were classified as AHA/ACC Type C (53.6%). Despite lesion complexity, device was successfully implanted at TL in 96.8%. MACE rate, reported on patients having completed 1-year follow-up (n = 203), was 6.6%, with low rate of definite/probable stent thrombosis (1.0%). CONCLUSIONS: In clinical practice of several Dutch sites, STENTYS Xposition S showed good procedural results and low 1-year clinical events rate, despite complex coronary anatomy.

Feasibility and observer reproducibility of speckle tracking echocardiography in congenital heart disease patients.

AIMS: The twisting motion of the heart has an important role in the function of the left ventricle. Speckle tracking echocardiography is able to quantify left ventricular (LV) rotation and twist. So far this new technique has not been used in congenital heart disease patients. The aim of our study was to investigate the feasibility and the intra- and inter-observer reproducibility of LV rotation parameters in adult patients with congenital heart disease. METHODS AND RESULTS: The study population consisted of 66 consecutive patients seen in the outpatient clinic (67% male, mean age 31 ± 7.7 years, NYHA class 1 ± 0.3) with a variety of congenital heart disease. First, feasibility was assessed in all patients. Intra- and inter-observer reproducibility was assessed for the patients in which speckle tracking echocardiography was feasible. Adequate image quality, for performing speckle echocardiography, was found in 80% of patients. The bias for the intra-observer reproducibility of the LV twist was 0.0°, with 95% limits of agreement of -2.5° and 2.5° and for interobserver reproducibility the bias was 0.0°, with 95% limits of agreement of -3.0° and 3.0°. Intra- and inter-observer measurements showed a strong correlation (0.86 and 0.79, respectively). Also a good repeatability was seen. The mean time to complete full analysis per subject for the first and second measurement was 9 and 5 minutes, respectively. CONCLUSION: Speckle tracking echocardiography is feasible in 80% of adult patients with congenital heart disease and shows excellent intra- and inter-observer reproducibility.

Diastolic abnormalities in normal phenotype hypertrophic cardiomyopathy gene carriers: a study using speckle tracking echocardiography.

BACKGROUND: Tissue Doppler imaging (TDI) of the mitral annulus has been proposed as an alternative for the identification of hypertrophic cardiomyopathy (HCM) genetically affected subjects without left ventricular hypertrophy (G+/LVH-). Unfortunately, conflicting results have been described in the literature, potentially caused by the angle-dependency of TDI. This study sought to assess abnormalities in mitral annular velocities in G+/LVH- subjects as detected by speckle tracking echocardiography (STE). METHODS: The study population consisted of 23 consecutive genotyped family members without major or minor criteria for the diagnosis of HCM (mean age 37 ± 13 years, 9 men) and 23 healthy volunteers (age 38 ± 12 years, 12 men) who prospectively underwent STE. RESULTS: There were no significant differences in global peak systolic annular velocity (7.4 ± 1.2 vs. 7.1 ± 1.0 cm/sec) and early diastolic annular velocity (10.2 ± 2.5 vs. 11.3 ± 2.2 cm/sec) between G+/LVH- and control subjects. Global peak late diastolic annular velocity was higher in G+/LVH- subjects (8.1 ± 1.7 vs. 5.7 ± 1.1 cm/sec, P < 0.001). Regionally, this difference was seen in all 6 studied LV walls. CONCLUSIONS: This STE study confirms our previous TDI observations on increased peak late diastolic annular velocities in G+/LVH- subjects. Because of the complete overlap in early diastolic annular velocities this parameter cannot be used in the genotypes we studied to differentiate genotype (+) from genotype (-) individuals.

Morphological characteristics of lesions with thin cap fibroatheroma-a substudy from the COMBINE (OCT-FFR) trial.

AIMS: To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). METHODS AND RESULTS: From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. CONCLUSION: Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

Prognosis of PCI in the Older Adult Population: Outcomes From the Multicenter Prospective e-ULTIMASTER Registry.

Background: Older adult patients undergoing percutaneous coronary intervention (PCI) are usually excluded from clinical trials. This study aimed to assess 1-year clinical outcomes in patients aged >80 years. Methods: This all-comer registry included patients who underwent PCI using the Ultimaster stent. Primary clinical endpoint was target lesion failure (TLF), a composite of cardiac death (CD), target vessel-related myocardial infarction (TV-MI), or clinically indicated target lesion revascularization (CD-TLR). Results: In total, 3286 (8.8%) patients aged ≥80 years were compared with 33,912 patients aged <80 years. The older adult patients included more women, had more comorbidities and exhibited more complex coronary anatomy. The incidence of TLF was higher in the older adult group (5.6% vs 3.0%, P < .0001), as well as for all-cause mortality (6.2% vs 1.7%, P < .0001), CD (3.3% vs 1.1%, P < .0001), and TV-MI (1.7% vs 0.8%, P < .0001), but not for CD-TLR (1.9% vs 1.7%, P = .15). After the inverse propensity score weighted analysis, aged ≥80 years was associated with increased risk of TLF (HR, 1.42; 95% CI, 1.22-1.66; P < .0001), CD (HR, 1.67; 95% CI, 1.136-2.06; P < .0001), and TV-MI (HR, 1.66; 95% CI, 1.24-2.24; P < .001) but not for CD-TLR (HR, 1.10; 95% CI, 0.85-1.43; P = .45). Conclusion: Older adult patients had a higher incidence of TLF, CD, and TV-MI but with no difference in the incidence of recurrent revascularization or stent thrombosis. Although PCI in older adults is relatively safe, higher rates of cardiac events should be considered.

Thin-Cap Fibroatheroma Rather Than Any Lipid Plaques Increases the Risk of Cardiovascular Events in Diabetic Patients: Insights From the COMBINE OCT-FFR Trial.

BACKGROUND: Autopsy studies have established that thin-cap fibroatheromas (TCFAs) are the most frequent cause of fatal coronary events. In living patients, optical coherence tomography (OCT) has sufficient resolution to accurately differentiate TCFA from thick-cap fibroatheroma (ThCFA) and not lipid rich plaque (non-LRP). However, the impact of OCT-detected plaque phenotype of nonischemic lesions on future adverse events remains unknown. Therefore, we studied the natural history of OCT-detected TCFA, ThCFA, and non-LRP in patients enrolled in the prospective multicenter COMBINE FFR-OCT trial (Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients). METHODS: In the COMBINE FFR-OCT trial, patients with diabetes and ≥1 lesion with a fractional flow reserve >0.80 underwent OCT evaluation and were clinically followed for 18 months. A composite primary end point of cardiac death, target vessel-related myocardial infarction, target-lesion revascularization, and hospitalization for unstable angina was evaluated in relation to OCT-based plaque morphology. RESULTS: A total of 390 patients (age 67.5±9 years; 63% male) with ≥1 nonischemic lesions underwent OCT evaluation: 284 (73%) had ≥1 LRP and 106 (27%) non-LRP lesions. Among LRP patients, 98 (34.5%) had ≥1 TCFA. The primary end point occurred in 7% of LRP patients compared with 1.9% of non-LRP patients (7.0% versus 1.9%; hazard ratio [HR], 3.9 [95% CI, 0.9-16.5]; P=0.068; log rank-P=0.049). However, within LRP patients, TCFA patients had a much higher risk for primary end point compared with ThCFA (13.3% versus 3.8%; HR, 3.8 [95% CI, 1.5-9.5]; P<0.01), and to non-LRP patients (13.3% versus 1.9%; HR, 7.7 [95% CI, 1.7-33.9]; P<0.01), whereas ThCFA patients had risk similar to non-LRP patients (3.8% versus 1.9%; HR, 2.0 [95% CI, 0.42-9.7]; P=0.38). Multivariable analyses identified TCFA as the strongest independent predictor of primary end point (HR, 6.79 [95% CI, 1.50-30.72]; P=0.013). CONCLUSIONS: Among diabetes patients with fractional flow reserve-negative lesions, patients carrying TCFA lesions represent only one-third of LRP patients and are associated with a high risk of future events while patients carrying LRP-ThCFA and non-LRP lesions portend benign outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02989740.

One-year performance of thin-strut cobalt chromium sirolimus-eluting stent versus thicker strut stainless steel biolimus-eluting coronary stent: a propensity-matched analysis of two international all-comers registries.

OBJECTIVES: Recent improvements in coronary stent design have focussed on thinner struts, different alloys and architecture, more biocompatible polymers, and shorter drug absorption times. This study evaluates safety and efficacy of a newer generation thin-strut cobalt chromium sirolimus-eluting coronary stent (SES, Ultimaster) in comparison with a second-generation thicker strut stainless steel biolimus-eluting stent (BES, Nobori) in percutaneous coronary intervention (PCI) practice. METHODS: A propensity score analysis was performed to adjust for differences in baseline characteristics of 8137 SES patients and 2738 BES patients of two PCI registries (e-Ultimaster and NOBORI 2). An independent clinical event committee adjudicated all endpoint-related adverse events. RESULTS: The use of SES, as compared with BES was associated with a significantly lower rate of myocardial infarction (MI) (1.2% vs 2.2%; P = 0.0006) and target vessel-related MI (1.1% vs 1.8%; P = 0.002) at 1 year. One-year composite endpoints of all predefined endpoints were lower in patients undergoing SES implantation (target lesion failure: 3.2% vs 4.1%; P = 0.03, target vessel failure: 3.7% vs 5.0%; P = 0.003, patient-oriented composite endpoint 5.7% vs 6.8%; P = 0.03). No significant differences between SES and BES were observed in all-cause death (2.0% vs 1.6%; P = 0.19), cardiac death (1.2% vs 1.2%; P = 0.76) or stent thrombosis (0.6% vs 0.8%; P = 0.43). CONCLUSIONS: These findings suggest an improved clinical safety and efficacy of a newer generation thin-strut SES as compared with a second-generation thicker strut BES.

Alterations in left ventricular untwisting with ageing.

BACKGROUND: In order to gain further insight into age-associated changes of left ventricular (LV) diastolic function, the purpose of the current study was to investigate alterations in LV untwisting with ageing. METHODS AND RESULTS: The study comprised 75 healthy volunteers, classified into 3 groups: age 16-35 (n=25), 36-55 (n=25) and 56-75 (n=25) years. LV untwisting (as a percentage of peak systolic twist) at 5%, 10%, 15% and 50% of diastole, peak diastolic untwisting velocity, time-to-peak diastolic untwisting velocity and untwisting rate (mean untwisting velocity during the time interval from peak systolic twist to mitral valve opening) were assessed using speckle-tracking echocardiography. Untwisting at 5%, 10%, 15% and 50% of diastole decreased with ageing. Although the peak diastolic untwisting velocity and untwisting rate were not significantly different between the age groups, when normalized for LV peak systolic twist, these parameters decreased with advancing age (both P<0.01). Time-to-peak diastolic untwisting velocity increased with ageing (P<0.01). CONCLUSIONS: Impairment of the relative peak diastolic untwisting velocity and untwisting rate, resulting in delayed LV untwisting, may help to explain diastolic dysfunction in the elderly. (Circ J 2010; 74: 101 - 108).