Impact of lipoprotein(a) levels on primary patency after endovascular therapy for femoropopliteal lesions.

Lipoprotein(a) [Lp(a)] is a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and clinical events after endovascular therapy (EVT) for the femoropopliteal artery in PAD patients remains unclear. Thus, this study aimed to assess the impact of Lp(a) levels on primary patency after EVT for de novo femoropopliteal lesions in PAD patients. A retrospective analysis was conducted on 109 patients who underwent EVT for de novo femoropopliteal lesions, and Lp(a) levels were measured before EVT between June 2016 and December 2019. Patients were divided into low Lp(a) [Lp(a) < 30 mg/dL; 78 patients] and high Lp(a) [Lp(a) ≥ 30 mg/dL; 31 patients] groups. The main outcome was primary patency following EVT. Loss of primary patency was defined as a peak systolic velocity ratio > 2.4 on a duplex scan or > 50% stenosis on angiography. Cox proportional hazards analysis was performed to determine whether high Lp(a) levels were independently associated with loss of primary patency. The mean follow-up duration was 28 months. The rates of primary patency were 83 and 76% at 1 year and 75 and 58% at 2 years in the low and high Lp(a) groups, respectively (P = 0.02). After multivariate analysis, High Lp(a)[Lp(a) ≥ 30 mg/dL] (hazard ratio 2.44; 95% CI 1.10-5.44; P = 0.03) and female sex (hazard ratio 2.65; 95% CI 1.27-5.51; P < 0.01) were independent predictors of loss of primary patency. Lp(a) levels might be associated with primary patency after EVT for de novo femoropopliteal lesions.

Potential of optical frequency domain imaging for differentiation between early and advanced coronary atherosclerosis.

PURPOSE: This study evaluated whether optical frequency domain imaging (OFDI) accurately distinguish between fibroatheroma (FA) and pathological intimal thickening (PIT) compared with histopathology. METHODS: A total of 631 histological cross-sections from 14 autopsy hearts were analyzed for the comparison between OFDI and histological images. Of those, 190 (30%) sections were diagnosed with PIT and 120 (19%) with FA. The OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally by detection of sequential OFDI frames within a plaque segment containing lipids. The lipid arc was measured with a protractor centered in the center of the lumen. The fibrous cap thickness was defined as the minimum thickness of the signal rich band overlying PIT and FA. RESULTS: There was no significant difference in the OFDI signal attenuation rate between FA and PIT (3.09 ± 1.04 versus 2.79 ± 1.20, p = 0.13). However, the lipid length was significantly longer, the maximum lipid arc was significantly larger, and the fibrous cap thickness was significantly thinner in FA than in PIT (7.5 [4.3-10.3] mm versus 4.3 [2.7-5.8] mm, p < 0.0001, 125 [101-174]° versus 96 [74-131]°, p < 0.0001, and 220 [167-280] µm versus 260 [190-332] µm, p = 0.019). CONCLUSIONS: This study revealed OFDI may have the potential capability for discriminating FA from PIT based on the longitudinal and circumferential extent of lipid plaque, although the OFDI signal attenuation rate was similar between FA and PIT.

Impact of lipoprotein (a) on long-term outcome after percutaneous coronary intervention in the era of new generation drug-eluting stents.

BACKGROUND: High lipoprotein (a) [Lp (a)] levels are associated with worse long-term outcomes in patients undergoing percutaneous coronary intervention (PCI). However, there are limited studies investigating association between Lp (a) levels and long-term outcomes in the era of new generation drug-eluting stents (DES). METHODS: A total of 495 patients with available data on Lp (a) who underwent PCI for de novo lesions with new generation DES were enrolled between 2013 and 2017. The primary endpoint was the major adverse cardiovascular event (MACE), which was defined as a composite of cardiac death, myocardial infarction, stent thrombosis, clinically driven target lesion revascularization, and revascularization for new lesions during 3 years. Patients were divided into 2 groups according to the Lp (a) level: high Lp (a) group (≥30 mg/dL: n = 109) and low Lp (a) group (30 mg/dL>: n = 386). Multivariate Cox regression analysis was performed to identify the predictors for 3-year MACE. RESULTS: The incidence of 3-year MACE was significantly higher in high Lp (a) group than low Lp (a) group (33.0% vs. 15.9%, p < 0.001). Multivariable analysis showed that Lp (a) level of ≥30 mg/dL was an independent predictor for 3-year MACE (HR 2.01, 95%CI 1.30-3.11, p = 0.002). CONCLUSION: High Lp (a) level was associated with worse long-term outcome even in the era of new generation DES.

Relationship Between Lipoprotein(a) and Angiographic Severity of Femoropopliteal Lesions.

AIM: High levels of lipoprotein(a) [Lp(a)] are a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and the severity of femoropopliteal lesions in patients with PAD has not been systematically studied. This study aimed to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD. METHODS: We retrospectively analyzed a single-center database including 108 patients who underwent endovascular therapy for de novo femoropopliteal lesions and measured the Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [Lp(a) ＜30 mg/dL; 77 patients] and high Lp(a) [Lp(a) ≥ 30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to the peripheral arterial calcium scoring system (PACSS) classification], and lesion length were compared between the groups. RESULTS: The prevalence of TASC II class D (13% vs 38%, P＜0.01) and severe calcification (PACSS 4) (6% vs 23%, P=0.02) was significantly higher and the lesion length longer (123±88 mm vs 175±102 mm, P＜0.01) in the high Lp(a) group than in the low Lp(a) group. In multivariate analysis, Lp(a) ≥ 30 was an independent predictor for the prevalence of TASC II class D (HR=3.67, 95% CI 1.27-10.6, P=0.02) and PACSS 4 (HR=4.97, 95% CI 1.27-19.4, P=0.02). CONCLUSION: The prevalence of TASC II class D and severe calcification of femoropopliteal lesions was higher in patients with high Lp(a) than those with low Lp(a).

Data-Driven Patient Clustering and Differential Clinical Outcomes in the Brigham and Women's Rheumatoid Arthritis Sequential Study Registry.

OBJECTIVE: To use unbiased, data-driven, principal component (PC) and cluster analysis to identify patient phenotypes of rheumatoid arthritis (RA) that might exhibit distinct trajectories of disease progression, response to treatment, and risk for adverse events. METHODS: Patient demographic, socioeconomic, health, and disease characteristics recorded at entry into a large, single-center, prospective observational registry cohort, the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS), were harmonized using PC analysis to reduce dimensionality and collinearity. The number of PCs was established by eigenvalue >1, cumulative variance, and interpretability. The resulting PCs were used to cluster patients using a K-means approach. Longitudinal clinical outcomes were compared between the clusters over 2 years. RESULTS: Analysis of 142 variables from 1,443 patients identified 41 PCs that accounted for 77% of the cumulative variance in the data set. Cluster analysis distinguished 5 patient clusters: 1) less RA disease activity/multimorbidity, shorter RA duration, lower incidence of comorbidities; 2) less RA disease activity/multimorbidity, longer RA duration, more infections, psychiatric comorbidities, health care utilization; 3) moderate RA disease activity/multimorbidity, more neurologic comorbidity; 4) more RA disease activity/multimorbidity, shorter RA duration, more metabolic comorbidity, higher body mass index; 5) more RA disease activity/multimorbidity, longer RA duration, more hepatic, orthopedic comorbidity and RA-related surgeries. The clusters exhibited differences in clinical outcomes over 2 years of follow-up. CONCLUSION: Data-driven analysis of the BRASS registry identified 5 distinct phenotypes of RA. These results illustrate the potential of data-driven patient profiling as a tool to support personalized medicine in RA. Validation in an independent data set is ongoing.

Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study.

OBJECTIVES: This study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment following conventional synthetic DMARDs, as well as potential modifiers of response, observed in US clinical practice. METHODS: Data were from a large US healthcare registry (Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis Registry). The analysis included patients (aged ≥18 years) with a documented diagnosis of rheumatoid arthritis (RA), a valid baseline Clinical Disease Activity Index (CDAI) score of >2.8 and no prior bDMARD or tsDMARD use. Outcomes were captured at 1-year postinitiation of a TNFi (adalimumab, etanercept, certolizumab pegol, golimumab or infliximab) or a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) and included CDAI, 28-Joint Modified Disease Activity Score, patient-reported outcomes (including the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, sleep, anxiety, morning stiffness and fatigue) and rates of anaemia. Groups were propensity score-matched at baseline to account for potential confounding. RESULTS: There were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for outcomes assessed, except the incidence rate ratio for anaemia, which slightly favoured the TNFi group (19.04 per 100 person-years) versus the non-TNFi group (24.01 per 100 person-years, p=0.03). No potential effect modifiers were found to be statistically significant. CONCLUSIONS: The findings of no significant differences in outcomes between first-line TNF versus first-line non-TNF groups support RA guidelines, which recommend individualised care based on clinical judgement and consideration of patient preferences.

Comparison of coronary atherosclerotic disease burden between ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: Non-culprit Gensini score and non-culprit SYNTAX score.

BACKGROUND: Patients with non-ST-elevation myocardial infarction (NSTEMI) have worse long-term prognoses than those with ST-elevation myocardial infarction (STEMI). HYPOTHESIS: It may be attributable to more extended coronary atherosclerotic disease burden in patients with NSTEMI. METHODS: This study consisted of consecutive 231 patients who underwent coronary intervention for myocardial infarction (MI). To assess the extent and severity of atherosclerotic disease burden of non-culprit coronary arteries, two scoring systems (Gensini score and synergy between percutaneous coronary intervention with Taxus and cardiac surgery [SYNTAX] score) were modified by subtracting the score of the culprit lesion: the non-culprit Gensini score and the non-culprit SYNTAX score. RESULTS: Patients with NSTEMI had more multi-vessel disease, initial thrombolysis in myocardial infarction (TIMI) flow grade 2/3, and final TIMI flow grade 3 than those with STEMI. As compared to STEMI, patients with NSTEMI had significantly higher non-culprit Gensini score (16.3 ± 19.8 vs. 31.2 ± 25.4, p < 0.001) and non-culprit SYNTAX score (5.8 ± 7.0 vs. 11.1 ± 9.7, p < 0.001). CONCLUSIONS: Patients with NSTEMI had more advanced coronary atherosclerotic disease burden including non-obstruction lesions, which may at least in part explain higher incidence of cardiovascular events in these patients.

Impact of Age on Gender Difference in Long-term Outcome of Patients With Acute Myocardial Infarction (from J-MINUET).

Although gender difference in long-term outcomes after acute myocardial infarction have been shown previously, impact of age on gender difference is still controversial. This study focused on the association between age and gender difference in long-term outcome. We analyzed data from 3,283 consecutive patients who were included in a prospective, nationwide, multicenter registry (Japan Registry of Acute Myocardial Infarction Diagnosed by Universal Definition) from 2012 to 2014. The primary end point was the major adverse cardiovascular event (MACE), which was defined as a composite of death, myocardial infarction, stroke, heart failure, and revascularization for unstable angina during 3 years. Patients were divided into 4 strata according to age: those with age <65 years (group 1: n = 1161), 65 to 74 years (group 2: n = 954), 75 to 84 years (group 3: n = 866) and 84< years (group 4: n = 302). Although the crude incidence of 3-year MACE was significantly higher in women than men (36.4% vs. 28.5%, p <0.001), there was not significant gender difference in each group (group 1, 19.6% vs 19.0%, p = 0.74; group 2, 33.1% vs 28.3%, p = 0.25; group 3, 38.9% vs 39.6%, p = 0.54; and group 4, 54.0% vs 56.8%, p = 0.24). In conclusion, although women had higher crude incidence of 3-year MACE than men, there was no gender difference in each group.

High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab.

BACKGROUND: Increased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL). This post hoc analysis of MONARCH phase III randomized controlled trial data evaluated the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab, a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor α (anti-IL-6Rα) versus adalimumab, a tumor necrosis factor α inhibitor, both approved for treatment of active RA. METHODS: Baseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6-7.1 pg/mL), medium (7.2-39.5 pg/mL), and high (39.6-692.3 pg/mL) tertiles. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale (AM-stiffness VAS). Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference. Pairwise comparisons of improvements between treatment groups were performed by tertile; least squares mean differences and 95% CIs were calculated. Similar analyses evaluated W24 patient-level response on minimum clinically important differences (MCID). RESULTS: At baseline, patients with high versus medium or low IL-6 levels (n = 100, respectively) reported worse (nominal p < 0.05) SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores. There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS (nominal interaction p < 0.05). PCS improvements ≥MCID were higher in high (odds ratio [OR] 6.31 [2.37, 16.81]) versus low (OR 0.97 [0.43, 2.16]) tertiles with sarilumab versus adalimumab (nominal interaction p < 0.05). Adverse events between IL-6 tertiles were similar. CONCLUSIONS: Patients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade. TRIAL REGISTRATION: NCT02332590 . Registered on 5 January 2015.

Influence of Self-Expanding Paclitaxel-Eluting Stent Sizing on Neointimal Hyperplasia in Superficial Femoral Artery Lesions.

BACKGROUND: Although self-expanding drug-eluting stents (DES) have recently shown superior outcomes for superficial femoral artery (SFA) lesions, optimal sizing of DES diameter in SFA intervention is unclear.Methods and Results:A total of 40 de novo SFA lesions were randomized 1:1 to receive self-expanding DES with either a 1-mm or 2-mm larger diameter than the reference vessel diameter. Follow-up optical coherence tomography (OCT) was scheduled 6 months after DES implantation to evaluate the vascular response to the stents. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was neointimal VI at 6 months. Baseline reference vessel diameter was similar between the 1-mm larger diameter group and the 2-mm larger diameter group (5.0±0.8 mm vs. 4.7±0.9 mm, P=0.35). Stent diameter was 6.3±0.6 mm in the 1-mm larger group and 7.1±0.6 mm in the 2-mm larger group (P<0.0001), and stent to reference vessel diameter ratio (SV ratio) was 1.3±0.2 and 1.5±0.2 (P<0.0001), respectively. At 6-month, neointimal VI was greater in the 2-mm larger diameter group (5.5±1.5 mm2vs. 9.6±3.4 mm2, P<0.001). The correlation analysis revealed that degree of neointimal VI was positively correlated with SV ratio (r=0.43, P<0.01). CONCLUSIONS: Implantation of self-expanding DES with a considerably high SV ratio resulted in neointimal hyperplasia in SFA lesions.

Efficacy and safety of sarilumab in combination with csDMARDs or as monotherapy in subpopulations of patients with moderately to severely active rheumatoid arthritis in three phase III randomized, controlled studies.

BACKGROUND: The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups. METHODS: Data were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200 mg every 2 weeks (q2w) either + MTX in MTX-IR patients (52 weeks) or + csDMARDs in TNF-IR/INT patients (24 weeks), and a monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w in MTX-IR/INT patients (24 weeks). Prespecified and post hoc subgroups included patient demographics, disease characteristics, and prior treatments. Prespecified and post hoc endpoints included clinical, radiographic, and physical function measures, and p values are considered nominal. Safety was assessed during double-blind treatment. RESULTS: The superiority of sarilumab (either as monotherapy vs. adalimumab or in combination with csDMARDs vs. placebo + csDMARDs) across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types. Interaction p values of < 0.05 were consistently observed across studies only for baseline anti-cyclic citrullinated peptide antibody (ACPA) status for American College of Rheumatology 20% response, but not American College of Rheumatology 50% or 70% response. Adverse events and worsening laboratory parameters occurred more frequently in sarilumab-treated vs. placebo-treated patients and were more frequent in the small number of patients ≥ 65 years (n = 289) vs. patients < 65 years (n = 1819). Serious infections occurred in six patients aged ≥ 65 years receiving sarilumab, although the incidence of serious infections was generally higher in patients aged ≥ 65 years regardless of treatment. CONCLUSIONS: Apart from ACPA status, there were no consistent signals indicating differential effects of sarilumab in any of the subpopulations assessed. Sarilumab demonstrated consistent efficacy and safety across a wide range of patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01061736, registered on February 03, 2010; ClinicalTrials.gov NCT01709578, registered on October 18, 2012; ClinicalTrials.gov NCT02332590, registered on January 07, 2015.

Association of High Serum Interleukin-6 Levels With Severe Progression of Rheumatoid Arthritis and Increased Treatment Response Differentiating Sarilumab From Adalimumab or Methotrexate in a Post Hoc Analysis.

OBJECTIVE: The development of biomarkers to guide treatment decisions is a major research focus in rheumatoid arthritis (RA). Patients with RA have elevated interleukin-6 (IL-6) levels; however, the utility of IL-6 as a predictor of treatment response is unclear. This study was undertaken to investigate, by post hoc analysis, whether baseline IL-6 levels are predictive of sarilumab treatment responses in 2 phase III studies. METHODS: Serum IL-6 concentrations were measured in patients with RA prior to receiving sarilumab 200 mg (n = 148) or adalimumab 40 mg (n = 152) every 2 weeks (in the MONARCH trial; ClinicalTrials.gov identifier: NCT02332590) or sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks plus methotrexate (MTX) (n = 401, n = 396, and n = 397, respectively) (in the MOBILITY trial; ClinicalTrials.gov identifier: NCT01061736). Efficacy and patient-reported outcomes were compared between and within groups according to IL-6 tertile using linear and logistic regression. RESULTS: In MONARCH, patients with high baseline IL-6 levels (all ≥3 times the upper limit of normal; n = 100) had higher disease activity at baseline than those with low IL-6 levels (n = 100). The magnitude of clinical improvement over 24 weeks with sarilumab versus adalimumab was greater in patients with high compared to those with low baseline IL-6 levels. In MOBILITY, compared to patients with low IL-6 levels (n = 397), patients with high IL-6 levels (n = 398) had higher disease activity and joint damage at baseline, were more likely to have joint progression, and had less clinical improvement over 52 weeks' treatment with placebo plus MTX compared to sarilumab 150 mg or 200 mg plus MTX. Baseline IL-6 and C-reactive protein levels were both predictive of outcomes. Safety profiles were similar between defined IL-6 tertiles. CONCLUSION: IL-6 may be a prognostic marker of disease progression and severity, and patients with high IL-6 levels may be likely to benefit from sarilumab compared to adalimumab or MTX. Prospective validation is warranted to confirm the results of these post hoc analyses.

Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes.

BACKGROUND: Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs. adalimumab. METHODS: In this post hoc analysis, serum samples were analysed at baseline and prespecified post-treatment timepoints up to week 24 in adults with moderate-to-severe active rheumatoid arthritis intolerant of or inadequate responders to methotrexate from the MONARCH trial (NCT02332590). RESULTS: Greater reductions in C-reactive protein (CRP; - 94.0% vs. -24.0%), serum amyloid A (SAA; - 83.2% vs. -17.4%), total receptor activator of nuclear factor-κB ligand (RANKL; - 18.3% vs. 10.5%) and lipoprotein (a) (- 41.0% vs. -2.8%) were observed at week 24 with sarilumab vs. adalimumab, respectively (adjusted p < 0.0001). Greater increases in procollagen type 1 N-terminal propeptide (P1NP) were observed with sarilumab vs. adalimumab at week 24 (22.8% vs. 6.2%, p = 0.027). Patients with high baseline SAA, CRP and matrix metalloproteinase-3 (MMP-3) were more likely to achieve clinical efficacy, including American College of Rheumatology 20% improvement criteria and Disease Activity Score (28 joints)-CRP < 3.2, and report improvements in patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and pain visual analogue scale, with sarilumab than adalimumab. CONCLUSION: Sarilumab was associated with greater positive effects on bone remodelling and decreases in biomarkers of the acute-phase response, synovial inflammation and cardiovascular risk vs. adalimumab. High baseline concentrations of SAA, CRP and MMP-3 are predictive of clinical and patient-reported outcome responses to sarilumab treatment and prospective validation is warranted to confirm these results. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02332590. Registered on 5 January 2015.

Impact of left ventricular diastolic dysfunction on long-term outcome in patients with lower extremity artery disease.

BACKGROUND: The relationship between long-term outcome in patients with lower extremity artery disease (LEAD) and left ventricular (LV) diastolic dysfunction has not been systematically studied. The aim of this study was to assess the impact of LV diastolic dysfunction on the long-term outcome in patients with LEAD. METHODS: Two hundred LEAD patients (male 66 %, mean age 76±9 years) with preserved LV systolic function assessed by echocardiography (ejection fraction ≥50 %) were enrolled from a single center database between January 2013 and May 2015. We divided the patients into two groups on the basis of LV diastolic dysfunction, which was diagnosed based on the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. The 3-year cumulative incidence of the primary endpoint was compared between LEAD patients with LV diastolic dysfunction and those without. The primary endpoint was a composite of major adverse cardiac and cerebrovascular events (MACCE: death, hospitalization for heart failure, myocardial infarction, and stroke). Multivariate analysis was performed to determine whether LV diastolic dysfunction was independently associated with the MACCE. RESULTS: LV diastolic dysfunction was identified in 31 % of LEAD patients. The mean observation period was 32±21 months. The 3-year cumulative incidence of MACCE occurred more frequently in patients with LV diastolic dysfunction than those without (35 % vs 23 %, p=0.01). In multivariate analysis, LV diastolic dysfunction (HR=1.96, 95 % CI 1.09-3.55, p=0.03) and critical limb ischemia (HR=2.52, 95 % CI 1.24-5.10, p=0.01) were an independent predictor for MACCE. CONCLUSION: LV diastolic dysfunction increased the risk for MACCE in patients with LEAD.

Pseudoaneurysm and subsequent venous thromboembolism after subintimal angioplasty for chronic total occlusion in the superficial femoral artery.

Endovascular therapy (EVT) has been accepted as a minimally invasive treatment for peripheral artery disease, and its applicability has been widened with the development of techniques and devices. A long, totally occluded lesion in the superficial femoral artery (SFA) is one of the most challenging lesions for EVT due to technical difficulties in wire-crossing. Recently, intentional subintimal recanalization is often considered as an alternative option for long SFA occlusions. Previous studies have shown that subintimal approach achieved superior technical success rate and similar patency rate, compared to conventional intraluminal approach. However, there is limited information about complications of the treatment with subintimal approach. Deep vein thrombosis (DVT) due to direct compression by pseudoaneurysm in the SFA, which subsequently develops pulmonary embolism (PE), is considered as a rare complication of subintimal angioplasty for the occlusive SFA lesion. We herein present a case of a patient who developed pseudoaneurysm formation in the SFA after EVT. Although initial EVT was performed successfully with subintimal approach, DVT and PE were caused by the SFA pseudoaneurysm at sub-acute phase following the initial procedure. The pseudoaneurysm was treated with implantation of a covered stent sealing the entry point, disappearing with no endoleak. .

Effects of Sarilumab on Rheumatoid Arthritis as Reported by Patients Using the Rheumatoid Arthritis Impact of Disease Scale.

OBJECTIVE: We evaluated the effect of sarilumab on patient-perceived impact of rheumatoid arthritis (RA) using the 7-domain RA Impact of Disease (RAID) scale. METHODS: Two phase III, randomized, controlled trials of sarilumab in patients with active, longstanding RA were analyzed: (1) sarilumab 150 mg and 200 mg every 2 weeks plus conventional synthetic disease-modifying antirheumatic drugs (+csDMARD) versus placebo + csDMARD [TARGET (NCT01709578)]; and (2) sarilumab 200 mg versus adalimumab (ADA) 40 mg monotherapy [MONARCH (NCT02332590)]. Least-squares mean (LSM) differences in RAID total score (range 0-10) and 7 key RA symptoms, including pain and fatigue (baseline to Weeks 12 and 24), were compared. "Responders" by RAID total score were defined by improvements from baseline ≥ minimal clinically important difference (MCID), and ≥ patient-acceptable symptom-state (PASS) at endpoint. RESULTS: Sarilumab 150 mg and 200 mg + csDMARD were nominally superior (p < 0.05) versus placebo + csDMARD and 200 mg sarilumab versus ADA 40 mg in LSM differences for RAID total score at weeks 12 (-0.93 and -1.13; -0.49, respectively) and 24 (-0.75 and -1.01; -0.78), and all effects of RA (except functional impairment in MONARCH Week 12). Effects were greater in physical domains (e.g., pain) than mental domains (e.g., emotional well-being). More patients receiving sarilumab versus placebo or ADA reported improvements ≥ MCID and PASS in total RAID scores at both assessments. CONCLUSION: Based on the RAID, sarilumab + csDMARD or as monotherapy reduced the effect of RA on patients' lives to a greater extent than placebo + csDMARD or ADA monotherapy. (ClinicalTrials.gov: NCT01709578 and NCT02332590).

Catheter-induced aortocoronary dissection at the ostium of anomalous left coronary artery during percutaneous coronary intervention for acute inferior myocardial infarction.

We report a case of catheter-induced aortocoronary dissection at the ostium of anomalous left coronary artery (LCA) during percutaneous coronary intervention (PCI) for acute inferior myocardial infarction (MI). Urgent coronary angiography revealed the culprit lesion of MI was the proximal segment of the right coronary artery (RCA). The anomalous LCA arose from the right sinus of Valsalva the same as the RCA. Catheter-induced aortocoronary dissection at the ostium of RCA was extended to the ostium of anomalous LCA by contrast injection. The patient fell into hemodynamic collapse due to acute occlusion of the anomalous LCA. The patient underwent successful bailout stenting at the ostium of anomalous LCA under percutaneous cardiopulmonary support (PCPS). He was weaned from PCPS system five days after PCI and was discharged. This is the first report about bailout procedure for catheter-induced aortocoronary dissection at the ostium of anomalous LCA. .

Open sesame technique in percutaneous coronary intervention for ST-elevation myocardial infarction.

In patients with ST-elevation myocardial infarction (STEMI), delays in reperfusion attenuate the benefit of primary percutaneous coronary intervention (PCI) and associate with higher mortality rates. Although PCI operators are making their best effort in time saving for reperfusion, it is sometimes challenging and takes time to pass the guide wire across the target lesions. A totally occluded lesion in which a side branch was bifurcating at the proximal end of the occluded segment is one of the most technically challenging anatomies of the target lesion because it is difficult to identify the entry point of the occluded segment. A side branch technique, termed "Open Sesame Technique" (OST), has been previously introduced for chronic total occlusion (CTO) lesion in which a side branch was bifurcating at the proximal end of the occluded segment. We herein present two cases applying this technique in STEMI with totally occluded lesions at bifurcation as a culprit lesion, in which the entry point was not identified on the initial angiography. PCI were performed successfully using the OST in both cases, which resulted in saving procedural time and contrast volume without any complications. This technique can be effective not only in PCI for CTO lesions but also in primary PCI for STEMI cases with occluded bifurcation lesions.