High triglyceride-glucose index is associated with adverse cardiovascular outcomes in patients with acute myocardial infarction

Background and aimsTriglyceride glucose (TyG) index is considered a new surrogate marker of insulin resistance that associated with the development of vascular disease. The aim of this study was to evaluate the prognostic value of TyG index in patients with acute myocardial infarction (AMI).Methods and resultsA total of 3181 patients with AMI were included in the analysis. Patients were stratified into 2 groups according to their TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. The incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), p = 0.010], cardiac death [HR (95% CI): 1.68 (1.19,2.38), p = 0.004], revascularization [HR (95% CI): 1.50 (1.16,1.94), p = 0.002], cardiac rehospitalization [HR (95% CI): 1.25 (1.05,1.49), p = 0.012], and composite MACEs [HR (95% CI): 1.19 (1.01,1.41), p = 0.046] in patients with AMI. The independent predictive effect of TyG index on composite MACEs was mainly reflected in the subgroups of male gender and smoker. The area under the curve (AUC) of the TyG index predicting the occurrence of MACEs in AMI patients was 0.602 [95% CI 0.580,0.623; p < 0.001].ConclusionHigh TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI.Trial registrationRetrospectively registered.     

Association between body mass index and mortality in atrial fibrillation patients with and without diabetes mellitus: Insights from a multicenter registry study in China

Background and aimsThe aim of this study was to evaluate the association between body mass index (BMI) and mortality in atrial fibrillation (AF) patients with and without diabetes mellitus (DM).Methods and resultsA total of 1991 AF patients were enrolled and divided into two groups according to whether they have DM at recruitment. Baseline information was collected and a mean follow-up of 1 year was carried out. The primary outcome was defined as all-cause mortality with the secondary outcomes including cardiovascular mortality, stroke and major adverse events (MAEs). Univariable and multivariable Cox regression were performed to estimate the association between BMI and 1-year outcomes in AF patients with and without DM. 309 patients with AF (15.5%) had comorbid DM at baseline. Patients with DM were more likely to have cardiovascular comorbidities, receive relevant medications but carry worse 1-year outcomes. Multivariable Cox regressions indicated that elevated BMI was related with reduced risk of all-cause mortality, cardiovascular mortality and major adverse events. Compared to normal weight, overweight [HR (95% CI): 0.548 (0.405–0.741), p < 0.001] and obesity [HR (95% CI): 0.541 (0.326–0.898), p = 0.018] were significantly related with decreased all-cause mortality for the entire cohort. Remarkably reduced all-cause mortality in the overweight [HR (95% CI): 0.497 (0.347–0.711), p < 0.001] and obesity groups [HR (95% CI): 0.405 (0.205–0.800), p = 0.009] could also be detected in AF patients without DM, but not in those with DM.ConclusionElevated BMI was associated with reduced mortality in patients with AF. This association was modified by DM. The obesity paradox confined to AF patients without DM, but could not be generalized to those with DM.     

Impact of surgical resection for gastrointestinal stromal tumor (GIST) patients with initially diagnosed synchronous hepatic metastases on long-term survival outcomes

BackgroundThe effect of surgical resection on the long-term outcome of GIST patients with initially diagnosed synchronous hepatic metastases in the targeted therapy era is still uncertain. The main aims of this study were to investigate the role of surgery in the treatment of these patients and establish clinical predictive models for assessing prognosis.MethodsWe identified these patients from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2018. The selection bias in comparisons was minimized by performing propensity score matching (PSM). The risk factors associated with long-term survival outcomes were identified by a Cox proportional hazards model and thus used to establish the nomograms. Nomograms were validated by concordance indexes (C-indexes), time-dependent receiver operator characteristic (ROC) curves, calibration plots, and decision curve analyses (DCA).ResultsOf these 523 eligible patients, there were 187 (35.8%) and 336 (64.2%) patients in the surgical and nonsurgical groups, respectively. Multivariate analysis revealed that surgical resection was an independent prognostic factor for OS (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.44–0.88, p = 0.0068) and CSS (HR 0.51; 95% CI 0.33 - 0.77, p = 0.0016). After PSM, it was found that surgical resection still showed significantly improved OS (5-year 54.9% vs 38.8%, p = 0.028) and CSS (5-year 65.8% vs 50.3%, p = 0.077). In addition, the C-indexes of the nomograms for OS and CSS prediction were 0.692 and 0.705, respectively, and the nomograms showed good consistency.ConclusionThis study revealed that surgical resection has a favorable impact on the long-term outcome of patients with synchronous GIST liver metastases, and the nomograms showed remarkable prediction performance for OS and CSS.     

Malnutrition status in patients of very advanced age with nonvalvular atrial fibrillation and its impact on clinical outcomes

Background and aimsMalnutrition is associated with adverse outcomes in patients with chronic disease. We screened malnutrition among patients of very advanced age with nonvalvular atrial fibrillation (AF) by malnutrition scores and investigated the associations between malnutrition and clinical outcomes.Methods and resultsThis retrospective observational study included 461 patients aged ≥80 years with nonvalvular AF. Malnutrition was screened using the Controlling Nutritional Status (CONUT), Prognostic Nutritional Index (PNI), and Geriatric Nutritional Risk Index (GNRI) scores. The primary endpoints were composite events, including thromboembolic events and all-cause death. Malnutrition was present in 62.9%, 5.0%, and 21.9% of patients according to the CONUT, PNI, and GNRI scores, respectively. During a median 27-month follow-up, 130 (28.2%) patients had composite events. Kaplan−Meier curves revealed that patients with moderate to severe malnutrition had the worst clinical outcomes (log-rank P < 0.05 for all scores). Multivariate Cox proportional hazards analysis showed that moderate to severe malnutrition was an independent predictor of composite events [hazard ratio (HR): 2.051, 95% confidence interval (95%CI): 1.143–3.679, P = 0.016 for CONUT score; HR: 3.374, 95%CI: 1.898–5.998, P < 0.001 for PNI score; HR: 2.254, 95%CI: 1.381–3.679, P = 0.001 for GNRI score]. Addition of the CONUT or GNRI score to a baseline prediction model for composite events significantly improved the net reclassification improvement and integrated discrimination improvement (all P < 0.05).ConclusionModerate to severe malnutrition was an independent predictor of adverse outcomes among patients of very advanced age with nonvalvular AF. Screening for malnutrition might provide useful information regarding prognosis and risk stratification.     

Prognostic role of modified Glasgow Prognostic score in elderly non-small cell lung cancer patients treated with anti-PD-1 antibodies

BackgroundThis study aimed to investigate whether the immunosenescence-related score is a critical prognostic predictor of anti-programmed cell death protein 1 (PD-1) axis inhibitors in elderly patients with advanced non-small cell lung cancer (NSCLC).MethodsWe reviewed 51 patients with advanced NSCLC aged ≥75 years, who were treated with nivolumab or pembrolizumab at the National Cancer Center Hospital between December 2015 and April 2019. Factors such as modified Glasgow prognostic score (mGPS), Neutrophil-to-lymphocyte ratio (NLR), and Charlson comorbidity index (CCI) were used to assess immunosenescence.ResultsThe objective response rate (ORR) and disease control rate (DCR) of all patients were 25.4% (95% confidence interval [CI]: 14.3–39.6) and 52.9% (95% CI: 38.5–67.1), respectively. High mGPS (score of 2) was associated with low DCR compared to low mGPS (score of 0–1) (26.0% vs. 54.0%, p = 0.03). However, none of these scores were significantly related to the ORR. High mGPS was significantly linked to shorter median progression-free survival (mPFS) (4.2 mos. vs. 12.7 mos, p < 0.01), and median overall survival (mOS) (4.8 mos. vs. 28.1 mos, p = 0.03). However, neither CCI nor NLR was associated with prognosis. Multivariate regression analysis identified high mGPS as a significant prognostic factor for mOS (hazard ratio, HR: 0.31 [95% CI: 0.13–0.71], p < 0.01).ConclusionsHigh mGPS scores significantly impaired DCR, mPFS, and mOS in patients with advanced NSCLC treated with anti-PD-1 antibodies.     

Impact of Diabetes on Outcome With Drug-Coated Balloons Versus Drug-Eluting Stents: The BASKET-SMALL 2 Trial

ObjectivesThe study sought to evaluate the impact of diabetes mellitus on 3-year clinical outcome in patients undergoing drug-coated balloon (DCB) or drug-eluting stent (DES) treatment for de novo lesions.BackgroundFor treatment of de novo coronary small vessel disease, DCBs are noninferior to DES.MethodsIn this prespecified analysis of a multicenter, randomized, noninferiority trial, including 758 patients with de novo lesions in coronary vessels <3 mm who were randomized 1:1 to DCB or DES and followed over 3 years for major adverse cardiac events (MACE) (cardiac death, nonfatal myocardial infarction [MI], and target vessel revascularization [TVR]), outcome was analyzed regarding the presence or absence of diabetes mellitus.ResultsIn nondiabetic patients (n = 506), rates of MACE (DCB 13.0% vs DES 11.5%; hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 0.73-2.09; P = 0.43), cardiac death (2.8% vs 2.9%; HR: 0.97; 95% CI: 0.32-2.92; P = 0.96), nonfatal MI (5.1% vs 4.8%; HR: 1.00; 95% CI: 0.44-2.28; P = 0.99), and TVR (8.8% vs 6.1%; HR: 1.64; 95% CI: 0.83-3.25; P = 0.16) were similar. In diabetic patients (n = 252), rates of MACE (19.3% vs 22.2%; HR: 0.82; 95% CI: 0.45-1.48; P = 0.51), cardiac death (8.8% vs 5.9%; HR: 2.01; 95% CI: 0.76-5.31; P = 0.16), and nonfatal MI (7.1% vs 9.8%; HR: 0.55; 95% CI: 0.21-1.49; P = 0.24) were similar in DCB and DES. TVR was significantly lower with DCBs vs DES (9.1% vs 15.0%; HR: 0.40; 95% CI: 0.17-0.94; P = 0.036; P = 0.011 for interaction).ConclusionsThe rates of MACE are similar in DCBs and DES in de novo coronary lesions of diabetic and nondiabetic patients. In diabetic patients, need for TVR was significantly lower with DCB versus DES. (Basel Stent Kosten Effektivitäts Trial Drug Eluting Balloons vs Drug Eluting Stents in Small Vessel Interventions [BASKET-SMALL2]; NCT01574534)     

Comparison of the effects of lenvatinib and sorafenib on survival in patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis

Background and aimThe first-line systemic therapy for advanced hepatocellular carcinoma (HCC) involves the use of sorafenib and lenvatinib. The present meta-analysis attempted to compare the therapeutic safety and effectiveness of the two drugs in advanced HCC.MethodsThe library databases of Cochrane, Embase, PubMed, and Web of Science were systematically searched to identify eligible studies comparing the long-term outcomes of sorafenib and lenvatinib use in advanced HCC patients. Overall survival (OS) was considered the primary endpoint, whereas the progression-free survival (PFS), severe adverse events (AEs), objective response rate (ORR), and disease control rate (DCR) were considered the secondary endpoints.ResultsThe present systematic review included 8 nonrandomized studies and 1 randomized controlled trial, comprising a total of 1, 914 cases. OS in patients receiving lenvatinib was better than that in patients receiving sorafenib [hazard ratio (HR): 1.23; 95% confidence interval (CI): 1.04–1.45]. Additionally, patients who received lenvatinib exhibited better PFS, ORR, and DCR (HR: 0.89, 95% CI: 0.79–0.99), [odds ratio (OR: 7.50, 95% CI: 4.43–12.69)], (OR: 7.50, 95% CI: 4.43–12.69), but higher incidences of AEs than those receiving sorafenib (OR: 1.28, 95% CI: 1.08–1.53).ConclusionLenvatinib is superior to sorafenib in treating unresectable HCC patients.     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial

BackgroundData on PCSK9 inhibition in chronic kidney disease (CKD) is limited.ObjectivesThe purpose of this study was to compare outcomes with evolocumab and placebo according to kidney function.MethodsThe FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized individuals with clinically evident atherosclerosis and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl or non–high-density lipoprotein cholesterol ≥100 mg/dl to evolocumab or placebo. The primary endpoint (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization), key secondary endpoint (cardiovascular death, myocardial infarction, or stroke), and safety were analyzed according to chronic kidney disease (CKD) stage estimated from CKD-epidemiology estimated glomerular filtration rate.ResultsThere were 8,077 patients with preserved kidney function, 15,034 with stage 2 CKD, and 4,443 with ≥stage 3 CKD. LDL-C reduction with evolocumab compared with placebo at 48 weeks was similar across CKD groups at 59%, 59%, and 58%, respectively. Relative risk reduction for the primary endpoint was similar for preserved function (hazard ratio [HR]: 0.82; 95% CI: 0.71 to 0.94), stage 2 (HR: 0.85; 95% CI: 0.77 to 0.94), and stage ≥3 CKD (HR: 0.89; 95% CI: 0.76 to 1.05); p_int = 0.77. Relative risk reduction for the secondary endpoint was similar across CKD stages (p_int = 0.75)—preserved function (HR: 0.75; 95% CI: 0.62 to 0.90), stage 2 (HR: 0.82; 95% CI: 0.72 to 0.93), stage ≥3 (HR: 0.79; 95% CI: 0.65 to 0.95). Absolute RRs at 30 months for the secondary endpoint were −2.5% (95% CI: -4.7% to -0.4%) for stage ≥3 CKD compared with −1.7% (95% CI: -2.8% to 0.5%) with preserved kidney function. Adverse events, including estimated glomerular filtration rate decline, were infrequent and similar regardless of CKD stage.ConclusionsLDL-C lowering and relative clinical efficacy and safety of evolocumab versus placebo were consistent across CKD groups. Absolute reduction in the composite of cardiovascular death, MI, or stroke with evolocumab was numerically greater with more advanced CKD. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633)     

Improved 3-Year Cardiac Survival After IVUS–Guided Long DES Implantation: A Patient-Level Analysis From 2 Randomized Trials

ObjectivesThe present study aimed to evaluate long-term cardiac survival benefit for intravascular ultrasound (IVUS)- versus angiography-guided long drug-eluting stent (DES) implantation.BackgroundAlthough the long-term benefit of IVUS guidance for DES implantation has been reported from recent randomized trials, this benefit was primarily driven by the reduction in repeat revascularization. Thus, it remains uncertain whether IVUS guidance improved survival during long-term follow-up.MethodsWe pooled the data of 2 randomized trials (IVUS-XPL [Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions] and ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions]) and compared IVUS guidance versus angiography guidance in 2,577 patients with long lesions treated with an implanted stent length ≥28 mm. The primary end point was cardiac death at 3 years.ResultsA 3-year clinical follow-up was completed in 96%. The primary end point of cardiac death occurred in 12 patients (1.0%) in the IVUS-guided group vs 28 patients (2.2%) in the angiography-guided group (HR: 0.43; 95% CI: 0.22-0.84; P = 0.011). In addition, target lesion–related myocardial infarction occurred in 3 patients (0.2%) in the IVUS-guided group and in 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95% CI: 0.09-1.22; P = 0.081), stent thrombosis developed in 3 patients (0.2%) in the IVUS-guided group and 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95% CI: 0.09-1.23; P = 0.082), and ischemia-driven target lesion revascularization was observed in 47 patients (3.8%) in the IVUS-guided group and 80 patients (6.5%) in the angiography-guided group (HR: 0.57; 95% CI: 0.40-0.82; P = 0.002).ConclusionsIn this post hoc pooled patient-level analysis, the use of IVUS-guided long DES implantation compared with angiography-guided stent implantation improved long-term patient cardiac survival.     

Neck circumference for predicting the occurrence of future cardiovascular events: A 7.6-year longitudinal study

Background & aimsThis study aimed to investigate whether neck circumference (NC) could be used to predict future cardiovascular (CV) events in a community-based Chinese cohort.Methods and resultsWe enrolled 1435 participants aged 50–80 years (men, 43.62%) from communities in Shanghai. High NC was defined as NC ≥ 38.5 cm in men and NC ≥ 34.5 cm in women. Kaplan-Meier analysis and Cox proportional hazards regression were performed to explore the association between NC and CV events. During a mean follow-up period of 7.6 years, 148 CV events (10.31%) occurred. The incidence of CV events was higher in men than in women (83 (13.26%) vs. 65 (8.03%), P = 0.002). Multivariable-adjusted Cox regression analysis showed that for every 1-SD increase in NC in the whole population, the hazard ratio (HR) of CV events was 1.45 (95% confidence interval [CI], 1.15–1.83). The dose-response association between NC and CV events was significant in men (HR, 1.37, 95% CI, 1.10–1.71) but not in women (HR, 1.19, 95% CI, 0.94–1.52). In comparison with participants showing low baseline NC, those with high baseline NC showed a significantly higher risk of CV events (HR, 1.59, 95% CI, 1.14–2.22). Further stratified by sex, the positive association remained significant in men (HR, 1.90, 95% CI, 1.21–2.98) but not in women (HR, 1.25, 95% CI, 0.75–2.07).ConclusionNC was significantly associated with the risk of future CV events in middle-aged and elderly populations in the community and was a better predictor in men.     

Association between the visceral adiposity index and risks of all-cause and cause-specific mortalities in a large cohort: Findings from the UK biobank

Background and aimsThe visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined.Methods and resultsIn this large-scale prospective epidemiological study, 357,457 participants (aged 38–73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148–1.255; P < 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150–1.303; P < 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148–1.255; P < 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148–1.255; P < 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25.ConclusionIn summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.     

Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction

BackgroundClonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.ObjectivesThe purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.MethodsThe study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.ResultsCHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology.ConclusionsSomatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.     

Long-Term Follow-Up of Hypoattenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement

BackgroundEarly hypoattenuated leaflet thickening (HALT) occurs in at least 10% of all transcatheter aortic valve replacement (TAVR) patients. The long-term prognostic impact of HALT is uncertain.ObjectivesThe aim of this study was to assess the long-term risk of early HALT post-TAVR.MethodsWe report outcome data from our prospective observational registry with post-TAVR computed tomography angiography performed between May 2012 and December 2017. The outcomes were survival, cardiovascular mortality, ischemic cerebrovascular events, and symptomatic hemodynamic valve deterioration.ResultsEarly HALT was diagnosed in 115 (16.0%) of 804 patients. During a median follow-up of 3.25 years, survival rates did not differ significantly between patients with and without HALT (Kaplan-Meier 3-year estimates for survival 70.1% vs 74.0%, P = 0.597). The 3-year cardiovascular mortality rate was 13.2% versus 11.3% (with vs without HALT, P = 0.733). The 3-year event rate for cerebrovascular events was 2.0% versus 4.4% (with vs without HALT, P = 0.246), and the 3-year event rate of symptomatic hemodynamic valve deterioration was 9.4% versus 1.5% (with vs without HALT, P < 0.001). Multivariable analysis revealed the following predictors of symptomatic hemodynamic valve deterioration: HALT (HR: 6.10; 95% CI: 2.59-14.29; P < 0.001), the mixed valve–type group (HR: 6.51; 95% CI: 2.38-17.81; P < 0.001), and prosthesis diameter (HR valve size per 3 mm [HR: 0.37; 95% CI: 0.17-0.79]; P = 0.011).ConclusionsDuring a median follow-up of more than 3 years, HALT was not associated with mortality or cerebrovascular events. However, we observed an association of HALT with symptomatic hemodynamic valve deterioration.     

Bleeding and Ischemic Outcomes With Ticagrelor Monotherapy According to Body Mass Index

BackgroundThere is a paucity of data regarding the safety and efficacy of different antiplatelet regimens according to standardized body mass index (BMI) categories.ObjectivesThe aim of this study was to investigate bleeding and ischemic outcomes according to BMI in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial.MethodsThe TWILIGHT trial randomized high-risk patients to ticagrelor plus aspirin or ticagrelor plus placebo at 3 months after percutaneous coronary intervention. In this secondary analysis, patients were stratified by standard BMI categories, as recommended by the European Society of Cardiology Working Group on Thrombosis (normal weight [BMI 18.5-24.99 kg/m²], overweight [BMI 25-29.99 kg/m²], and obese [BMI ≥30 kg/m²]) and by median BMI, as prespecified in the protocol.ResultsAmong 7,038 patients randomized and with available BMI, 1,807 (25.7%) were normal weight, 2,927 (41.6%) were overweight, and 2,304 (32.7%) were obese. In normal-weight, overweight, and obese patients, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced the primary endpoint of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (normal weight: HR: 0.48 [95% CI: 0.32-0.73]; overweight: HR: 0.57 [95% CI: 0.41-0.78]; obese: HR: 0.63 [95% CI: 0.44-0.91]; P for interaction = 0.627), without any increase in the composite ischemic endpoint of all-cause death, myocardial infarction, or stroke (normal weight: HR: 1.36 [95% CI: 0.84-2.19]; overweight: HR: 0.92 [95% CI: 0.63-1.35]; obese: HR: 0.84 [95% CI: 0.56-1.25]; P for interaction = 0.290). These findings were consistent with the prespecified analysis by median BMI.ConclusionsAmong high-risk patients undergoing percutaneous coronary intervention, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced bleeding events without any increase in ischemic risk across different BMI categories.     

Prognostic value of frontal QRS-T angle in predicting survival after primary percutaneous coronary revascularization/coronary artery bypass grafting for ST-elevation myocardial infarction

BackgroundFrontal QRS-T angle (FQRST) has previously been correlated with mortality in patients with stable coronary artery disease, but its role as survival predictor after ST-elevation myocardial infarction (STEMI) remains unknown.MethodsWe evaluated 267 consecutive patients with STEMI undergoing reperfusion or coronary artery bypass grafting. Data assessed included demographics, clinical presentation, electrocardiograms, medical therapy, and one-year mortality.ResultsOf 267 patients, 187 (70%) were males and most (49.4%) patients were Caucasian. All-cause mortality was significantly higher among patients with the highest (101–180°) FQRST [28% vs. 15%, p = 0.02]. Patients with FQRST 1–50° had higher survival (85.6%) compared with FQRST = 51–100° (72.3%) and FQRST = 101–180° (67.9%), [log rank, p = 0.01]. Adjusting for significant variables identified during univariate analysis, FQRST (OR = 2.04 [95% CI: 1.31–13.50]) remained an independent predictor of one-year mortality. FQRST-based risk score (1–50° = 0 points, 51–100° = 2 points, 101–180° = 5 points) had excellent discriminatory ability for one-year mortality when combined with Mayo Clinic Risk Score (C statistic = 0.875 [95%CI: 0.813–0.937]. A high (>4 points) FQRST risk score was associated with greater mortality (32% vs. 19%, p = 0.02) and longer length of stay (6 vs. 2 days, p < 0.001).ConclusionFQRST represents a novel independent predictor of one-year mortality in patients with STEMI undergoing reperfusion. A high FQRST-based risk score was associated with greater mortality and longer length of stay and, after combining with Mayo Clinic Risk Score, improved discriminatory ability for one-year mortality.     

Vascular Quality Initiative Surveillance of Femoropopliteal Artery Paclitaxel Devices

ObjectivesThis study sought to determine the safety and efficacy of paclitaxel (PTX) devices in the treatment of peripheral artery disease involving the femoropopliteal artery.BackgroundA meta-analysis of PTX devices for the treatment of femoropopliteal artery disease reported a mortality signal.MethodsThis was a multicenter cohort study using an integrated clinical data surveillance system to conduct a prospective, propensity score–matched survival analysis of 2,456 patients in the Society for Vascular Surgery Vascular Quality Initiative from January 2017 to May 2020. The study compared PTX drug-coated balloon angioplasty versus percutaneous transluminal balloon angioplasty, PTX drug-eluting stents versus bare-metal stents, and any PTX device versus any non-PTX device. The primary outcome was 2-year survival. Secondary endpoints were successful ambulation and interventional success.ResultsTreatment with any PTX device versus any non-PTX device was associated with increased 2-year survival (89.5% vs 86.7%; HR: 0.79; 95% CI: 0.72-0.87; P = 0.004), improved interventional success (81.6% vs 77.6%; HR: 0.82; 95% CI: 0.74-0.91; P < 0.001), and higher rates of independent ambulation at 1 year (86.0% vs 83.4%; HR: 0.85; 95% CI: 0.79-0.91; P = 0.008). Treatment with PTX drug-coated balloon angioplasty was associated with improved survival at 2 years (88.9% vs 85.7%; HR: 0.77; 95% CI: 0.70-0.86; P = 0.005), while PTX drug-eluting stent therapy was associated with similar survival compared with bare-metal stent therapy (91.3% vs 89.6%; HR: 0.84; 95% CI: 0.70-1.01; P = 0.36).ConclusionsIn this prospective, active surveillance of a national clinical registry, PTX-containing devices were associated with increased survival at 2 years and improved clinical outcomes at 1 year. (VQI DELTA Paclitaxel Device Safety Analysis [VQI-PTX]; NCT04110288)     

Prevalence of pulmonary embolism in patients with obstructive sleep apnea and chronic obstructive pulmonary disease: The overlap syndrome

ObjectiveGrowing evidence indicates that both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may be closely associated with the prevalence of pulmonary embolism (PE). However, the relationship of overlap syndrome (OS) (coexistence of OSA and COPD) with PE is unclear. The purpose of this study was to investigate whether OS were associated with increased PE prevalence.MethodsWe performed a retrospective chart review of patients who underwent sleep study at Beijing An Zhen Hospital from 2011 to 2014. The association of OS with PE prevalence was estimated by using logistic regression models.ResultsIn contrast to control patients (neither OSA nor COPD), those subjects with OS had higher odds of PE (OR9.61; 95%CI 4.02–21.31, p < 0.001) with significance persisting after adjusting for covariates (OR 5.66; 95%CI 1.80–16.18, p = 0.004). Meanwhile, patients with OS compared with those with isolated OSA also had significantly higher odds of PE in univariate (OR 4.79; 95%CI 2.04–10.33, p = 0.0007) and adjusted models (OR 3.89; 95%CI 1.27–10.68, p = 0.019). In subgroup analysis, patients with OS had higher odds of PE than control group among male subjects (OR 8.12, 95%CI1.86–31.87, p = 0.007) and patients ≥ 58years (OR 5.50, 95%CI 1.51–18.14, p = 0.012) in multivariable models. Percentage of total sleep time with saturation lower than 90% (T90) ≥ 2.6% was significantly associated with prevalence of PE (OR 4.72, 95%CI1.34–19.83, p = 0.015) in subgroup of patients older than 58.ConclusionsOS is independently associated with PE prevalence. Longitudinal studies are needed to better understand the relationship with incident PE.     

Chemotherapy versus best supportive care in advanced lung cancer and idiopathic interstitial pneumonias: A retrospective multi-centre cohort study

BackgroundThe clinical questions of whether chemotherapy as initial treatment, compared with best supportive care (BSC), improves overall survival (OS) and whether it increases the occurrence risk of acute exacerbation of idiopathic interstitial pneumonia (IIP) in patients with advanced-stage lung cancer and IIP remain inconclusive. This study addresses these issues, given that chemotherapy-related acute exacerbation of IIP may be a direct cause of mortality in these patients.MethodsWe enrolled 1003 patients from 110 Japanese institutions and collected clinical profiles from 707 and 296 patients in the chemotherapy (men: women, 645:62; mean age, 70.4 ± 6.9 years) and BSC (men: women, 261:35; mean age, 75.2 ± 7.8) groups, respectively. We used propensity score matching to create 222 matched pairs from both groups using patient demographic data (age, sex, smoking status, performance status, history of acute exacerbation of IIP, desaturation on exertion, clinical diagnosis of IIP, high-resolution computed tomography findings, serum fibrotic markers, pulmonary function status, and lung cancer histopathology). Logistic or Cox regression analyses were performed using matched data to assess the effects of chemotherapy on the risk of acute exacerbation of IIP or OS, respectively.ResultsIn the well-matched cohort, chemotherapy improved OS (hazard ratio: 0.629, 95% confidence interval [CI]: 0.506–0.783, p < 0.0001); however, it involved significant acute exacerbation of IIP (odds ratio: 1.787, 95% CI: 1.026–3.113) compared to BSC.ConclusionsCompared with BSC, chemotherapy can improve OS in patients with advanced-stage lung cancer and IIP; however, it increases the risk of acute exacerbation of IIP.