Impact of chronic thrombocytopenia on healthcare resource utilization, in-hospital outcomes, and costs following percutaneous coronary intervention of chronic total occlusion: a nationwide propensity weighted analysis.

BACKGROUND: Data on the impact of chronic thrombocytopenia (CT) on outcomes following chronic total occlusion (CTO) percutaneous coronary interventions (PCI) is limited. Most studies are case reports and focused on postprocedural thrombocytopenia. The purpose of this present study is to assess the impact of CT (> one year) on health resource utilization (HRU), in-hospital outcomes, and cost following CTO PCI. METHODS: We used discharge data from the 2016-2018 National Inpatient Sample and propensity score-weighted approach to examine the association between CT and HRU among patients undergoing CTO PCI. HRU was measured as a binary indicator defined as a length of stay greater than seven days and/or discharge to a non-home setting. The cost was measured as total charges standardized to 2018 dollars. Both outcomes were assessed using generalized linear models adjusted for survey year, and baseline characteristics. RESULTS: Relative to its absence, the presence of CT following CTO PCI was associated with a 4.8% increased probability of high HRU (Population Average Treatment Effect (PATE) estimate = 0.048; 95% Confidence Interval (CI) = 0.041-0.055; P<0.001) and approximately $18,000 more in total hospital charges (PATE estimate = +$18,297.98; 95% CI = $15,101.33-$21,494.63, P<0.001). CONCLUSION: Among chronic total occlusion patients undergoing percutaneous coronary intervention, those with chronic thrombocytopenia had higher resource use, including total hospital charges, and worse in-hospital outcomes when compared with those without chronic thrombocytopenia.

Angiographic characteristics of patients with STEMI and COVID-19: Insights from NACMI registry.

BACKGROUND: To date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI. METHODS: Angiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed. RESULTS: From 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51). CONCLUSION: In patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality.

ST-Segment Elevation Myocardial Infarction Caused by 5-Fluorouracil-Related Cardiotoxicity.

5-Fluorouracil (5-FU) and its prodrug, capecitabine, are commonly used chemotherapeutic agents for solid tumor management. While these agents can present with adverse side effects such as nausea, vomiting, diarrhea, and myelosuppression, they can also, less commonly, cause cardiovascular toxicity. This toxicity may manifest as cardiac arrhythmias, myocarditis, heart failure, myocardial infarction, and even death. The management of 5-FU-related cardiotoxicity includes early recognition of symptom manifestation so that medication can be discontinued promptly and symptoms can be addressed appropriately. Here, we describe the case of a 72-year-old male who developed coronary vasospasm and ST-segment elevation myocardial infarction shortly after the initiation of chemotherapy with 5-FU.

Comparative Healthcare Resource Utilization of Percutaneous Mechanical Circulatory Support Using Impella Versus Intra-aortic Balloon Pump Use for Patients With Acute Coronary Syndrome and Cardiogenic Shock Undergoing Percutaneous Coronary Interventions: Insights From National Inpatient Sample.

The use of percutaneous mechanical circulatory support (MCS) devices, including Impella and Intra-aortic balloon pump (IABP), in patients with cardiogenic shock has increased in recent times. We aimed to evaluate the impact of the choice of an MCS device on healthcare resource utilization. We queried the National Inpatient Sample registry between October 2016 and December 2018 to identify adults admitted for acute coronary syndrome-related cardiogenic shock and who received percutaneous coronary intervention (PCI). The study population was segregated into Impella and IABP groups using ICD 10 diagnosis codes. The primary endpoint was high healthcare resource utilization (HRU), while secondary outcomes included periprocedural complications. Propensity scoring matching was used to determine which patients in the Impella cohort had similar health to IABP patients. During the study period, 439,610 patients were admitted who received hemodynamic support using, Impella or IABP on account of acute coronary syndrome complicated by cardiogenic shock (CS). The median age (years) of the Impella cohort and IABP cohorts were similar (64.1 vs 65.1, P = 0.08). Gender distribution of the Impella CS patients was like IABP patients with female majorities in both groups, (71.9% vs 67.9%, P = 0.05). Impella CS patients had a higher representation of those with hypertension (P = 0.002), smoking (P = 0.040), obesity (P = 0.034), diabetes mellitus (P = 0.009), CHF (P = 0.030), COPD (P = 0.034), chronic liver disease (P = 0.028), and chronic kidney disease (P = 0.031). 1:1 Propensity score matching identified 2620 Impella patients' comparable severity index with the IABP patients. Patients with hemodynamic support using Impella had higher healthcare resource utilization, (HRU), the surrogate of length of stay (LOS) ≥7 or nonhome disposition at discharge, when compared with those with IABP (57.41% vs 42.76%, P < 0.0001). Impella CS patients had higher in-hospital mortality as compared to the IABP patients (55.45% vs 45.86%, P < 0.0001). Impella CS patients developed more periprocedural complications, including vascular injury (4.8% vs 1.4%, P < 0.0001), acute kidney injury (58.36% vs 41.64%, P < 0.0001), end-stage renal disease requiring dialysis (8.75% vs 1.25%, P = 0.002) when compared to the IABP patients. Among patients with ACS undergoing PCI and receiving MCS devices, those receiving Impella demonstrated higher healthcare resource utilization, higher LOS ≥7 days, and more nonhome disposition at discharge compared to patients receiving IABP. Further investigation is warranted to elucidate factors associated with these findings.

The role of multidetector CT scan in the management of prosthetic aortic valve thrombosis: A case report.

Key Clinical Message: In this case report, the utility of MDCT in elucidating the pathophysiology and etiology of prosthetic aortic valve dysfunction allowed us to distinguish thrombosis from pannus as an etiology of prosthetic valve dysfunction. MDCT also guided the success of therapy. Abstract: The diagnosis and management of prosthetic aortic valve thrombosis (PAVT) is challenging. The accurate diagnosis of this entity and its prompt management is vital to improving the prognosis of PAVT patients. Multidetector CT plays a central role in this effort. We present a case of PAVT in which the use of MDCT was useful in guiding management.

Comparative Analysis of Patients With STEMI and COVID-19 Between Canada and the United States.

Background: Important health care differences exist between the United States (US) and Canada, which may have been exacerbated during the pandemic. We compared clinical characteristics, treatment strategies, and clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 (STEMI-COVID) treated in the US and Canada. Methods: The North American COVID-19 Myocardial Infarction registry is a prospective, investigator-initiated study enrolling patients with STEMI with confirmed or suspected COVID-19 in the US and Canada. The primary end point was in-hospital mortality. Additionally, we explored associations between vaccination and clinical outcomes. Results: Of 853 patients with STEMI-COVID, 112 (13%) were enrolled in Canada, and compared with the US, patients in Canada were more likely to present with chest pain and less likely to have a history of heart failure, stroke/transient ischemic attack, pulmonary infiltrates or renal failure. In both countries, the primary percutaneous coronary intervention was the dominant reperfusion strategy, with no difference in door-to-balloon times; fibrinolysis was used less frequently in the US than in Canada. The adjusted in-hospital mortality was not different between the 2 countries (relative risk [RR], 1.0; 95% CI, 0.46-2.72; P = 1.0). However, the risk of in-hospital mortality was significantly higher in unvaccinated compared with vaccinated patients with STEMI-COVID (RR, 4.7; 95% CI, 1.7-11.53; P = .015). Conclusions: Notable differences in morbidities and reperfusion strategies were evident between patients with STEMI-COVID in the US compared with Canada. No differences were noted for in-hospital mortality. Vaccination, regardless of region, appeared to associate with a lower risk of in-hospital mortality strongly.

A Review of ST-Elevation Myocardial Infarction in Patients with COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

Mechanical Circulatory Support in Patients With COVID-19 Presenting With Myocardial Infarction.

ST-segment elevation myocardial infarction (STEMI) complicating COVID-19 is associated with an increased risk of cardiogenic shock and mortality. However, little is known about the frequency of use and clinical impact of mechanical circulatory support (MCS) in these patients. We sought to define patterns of MCS utilization, patient characteristics, and outcomes in patients with COVID-19 with STEMI. The NACMI (North American COVID-19 Myocardial Infarction) is an ongoing prospective, observational registry of patients with COVID-19 positive (COVID-19+) with STEMI with a contemporary control group of persons under investigation who subsequently tested negative for COVID-19 (COVID-19-). We compared the baseline characteristics and in-hospital outcomes of COVID-19+ and patients with COVID-19- according to the use of MCS. The primary outcome was a composite of in-hospital mortality, stroke, recurrent MI, and repeat unplanned revascularization. A total of 1,379 patients (586 COVID-19+ and 793 COVID-19-) enrolled in the NACMI registry between January 2020 and November 2021 were included in this analysis; overall, MCS use was 12.3% (12.1% [n = 71] COVID-19+/MCS positive [MCS+] vs 12.4% [n = 98] COVID-19-/MCS+). Baseline characteristics were similar between the 2 groups. The use of percutaneous coronary intervention was similar between the groups (84% vs 78%; p = 0.404). Intra-aortic balloon pump was the most frequently used MCS device in both groups (53% in COVID-19+/MCS+ and 75% in COVID-19-/MCS+). The primary outcome was significantly higher in COVID-19+/MCS+ patients (60% vs 30%; p = 0.001) because of very high in-hospital mortality (59% vs 28%; p = 0.001). In conclusion, patients with COVID-19+ with STEMI requiring MCS have very high in-hospital mortality, likely related to the significantly higher pulmonary involvement compared with patients with COVID-19- with STEMI requiring MCS.

A Review of ST-Elevation Myocardial Infarction in Patients with COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

North American COVID-19 Myocardial Infarction (NACMI) Risk Score for Prediction of In-Hospital Mortality.

Background: In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is higher in those with COVID-19 than in those without COVID-19. The factors that predispose to this mortality rate and their relative contribution are poorly understood. This study developed a risk score inclusive of clinical variables to predict in-hospital mortality in patients with COVID-19 and STEMI. Methods: Baseline demographic, clinical, and procedural data from patients in the North American COVID-19 Myocardial Infarction registry were extracted. Univariable logistic regression was performed using candidate predictor variables, and multivariable logistic regression was performed using backward stepwise selection to identify independent predictors of in-hospital mortality. Independent predictors were assigned a weighted integer, with the sum of the integers yielding the total risk score for each patient. Results: In-hospital mortality occurred in 118 of 425 (28%) patients. Eight variables present at the time of STEMI diagnosis (respiratory rate of >35 breaths/min, cardiogenic shock, oxygen saturation of <93%, age of >55 â€‹years, infiltrates on chest x-ray, kidney disease, diabetes, and dyspnea) were assigned a weighted integer. In-hospital mortality increased exponentially with increasing integer risk score (Cochran-Armitage χ2, P â€‹< â€‹.001), and the model demonstrated good discriminative power (c-statistic â€‹= â€‹0.81) and calibration (Hosmer-Lemeshow, P â€‹= â€‹.40). The increasing risk score was strongly associated with in-hospital mortality (3.6%-60% mortality for low-risk and very high-risk score categories, respectively). Conclusions: The risk of in-hospital mortality in patients with COVID-19 and STEMI can be accurately predicted and discriminated using readily available clinical information.

Trends in Clinical Presentation, Management, and Outcomes of STEMI in Patients With COVID-19.

BACKGROUND: We previously reported high in-hospital mortality for ST-segment elevation myocardial infarction (STEMI) patients with COVID-19 treated in the early phase of the pandemic. OBJECTIVES: The purpose of this study was to describe trends of COVID-19 patients with STEMI during the course of the pandemic. METHODS: The NACMI (North American COVID-19 STEMI) registry is a prospective, investigator-initiated, multicenter, observational registry of hospitalized STEMI patients with confirmed or suspected COVID-19 infection in North America. We compared trends in clinical characteristics, management, and outcomes of patients treated in the first year of the pandemic (January 2020 to December 2020) vs those treated in the second year (January 2021 to December 2021). RESULTS: A total of 586 COVID-19-positive patients with STEMI were included in the present analysis; 227 treated in Y2020 and 359 treated in Y2021. Patients' characteristics changed over time. Relative to Y2020, the proportion of Caucasian patients was higher (58% vs 39%; P < 0.001), patients presented more frequently with typical ischemic symptoms (59% vs 51%; P = 0.04), and patients were less likely to have shock pre-PCI (13% vs 18%; P = 0.07) or pulmonary manifestations (33% vs. 47%; P = 0.001) in Y2021. In-hospital mortality decreased from 33% (Y2020) to 23% (Y2021) (P = 0.008). In Y2021, none of the 22 vaccinated patients expired in hospital, whereas in-hospital death was recorded in 37 (22%) unvaccinated patients (P = 0.009). CONCLUSIONS: Significant changes have occurred in the clinical characteristics and outcomes of STEMI patients with COVID-19 infection during the course of the pandemic.

High-Sensitivity Troponin I Levels and Coronary Artery Disease Severity, Progression, and Long-Term Outcomes.

BACKGROUND: The associations between high-sensitivity troponin I (hsTnI) levels and coronary artery disease (CAD) severity and progression remain unclear. We investigated whether there is an association between hsTnI and angiographic severity and progression of CAD and whether the predictive value of hsTnI level for incident cardiovascular outcomes is independent of CAD severity. METHODS AND RESULTS: In 3087 patients (aged 63±12 years, 64% men) undergoing cardiac catheterization without evidence of acute myocardial infarction, the severity of CAD was calculated by the number of major coronary arteries with ≥50% stenosis and the Gensini score. CAD progression was assessed in a subset of 717 patients who had undergone ≥2 coronary angiograms >3 months before enrollment. Patients were followed up for incident all-cause mortality and incident cardiovascular events. Of the total population, 11% had normal angiograms, 23% had nonobstructive CAD, 20% had 1-vessel CAD, 20% had 2-vessel CAD, and 26% had 3-vessel CAD. After adjusting for age, sex, race, body mass index, smoking, hypertension, diabetes mellitus history, and renal function, hsTnI levels were independently associated with the severity of CAD measured by the Gensini score (log 2 ß=0.31; 95% confidence interval, 0.18-0.44; P<0.001) and with CAD progression (log 2 ß=0.36; 95% confidence interval, 0.14-0.58; P=0.001). hsTnI level was also a significant predictor of incident death, cardiovascular death, myocardial infarction, revascularization, and cardiac hospitalizations, independent of the aforementioned covariates and CAD severity. CONCLUSIONS: Higher hsTnI levels are associated with the underlying burden of coronary atherosclerosis, more rapid progression of CAD, and higher risk of all-cause mortality and incident cardiovascular events. Whether more aggressive treatment aimed at reducing hsTnI levels can modulate disease progression requires further investigation.

Transcatheter Aortic Valve Replacement in Patients With Aortic Stenosis and Mitral Regurgitation.

BACKGROUND: Many patients undergoing transcatheter aortic valve replacement (TAVR) for aortic stenosis also have significant mitral regurgitation (MR). We sought to understand the association of concomitant MR with TAVR clinical outcomes, as well changes in MR after TAVR. METHODS: Patients who underwent TAVR in the US Transcatheter Valve Therapy Registry from January 3, 2012, to December 31, 2013, were studied, with longer-term clinical outcomes from Center for Medicare Services data. RESULTS: Of 11,104 patients, 3,481 (31.3%) had moderate MR, and 605 (5.5%) had severe MR. At 1 year, mortality was 21.0%, 21.5%, 26.3%, and 28.0% (p < 0.0001) and heart failure (HF) rehospitalization was 13.9%, 15.8%, 20.3%, and 23.4% (p < 0.0001) in the no, mild, moderate, and severe MR patients, respectively. After adjustment for baseline differences, significant MR was associated with increased risk of 1-year mortality or HF rehospitalization, with a HR of 1.16 (95% CI, 0.99 to 1.35) for moderate MR and 1.21 (95% CI, 0.97 to 1.50) for severe MR, compared with no MR. MR improved early after TAVR grade ≥ 1 in 79% of the severe MR patients and 66% of the moderate MR patients. Patients whose baseline moderate or severe MR improved had lower mortality (p = 0.022) and HF rehospitalization (p < 0.001) compared with patients whose MR did not improve. CONCLUSIONS: Moderate or severe MR accompanying severe AS treated with TAVR is associated with increased mortality or HF rehospitalization. This increased risk may be attributable to the minority of patients whose MR does not improve, suggesting a potential role for surveillance and targeted intervention for those patients.

Association between oxidative stress and atrial fibrillation.

BACKGROUND: Oxidative stress (OS) may be a key mechanism underlying the development of atrial fibrillation (AF) in experimental studies, but data in humans remain limited. OBJECTIVE: Systemic OS can be estimated by measurements of circulating levels of the aminothiols including glutathione, cysteine, and their oxidized products. We tested the hypothesis that the redox potentials of glutathione (EhGSH) and cysteine will be associated with prevalent and incident AF. METHODS: Plasma levels of aminothiols were measured in 1439 patients undergoing coronary angiography, of whom 148 (10.3%) had a diagnosis of AF. After a median follow-up of 6.3 years, 104 of 917 patients (11.5%) developed incident AF. Multivariate logistic regression and Cox regression models were used to determine whether OS markers were independent predictors of prevalent and incident AF after adjustment for traditional risk factors, heart failure, coronary artery disease, and high-sensitivity C-reactive protein level. RESULTS: For each 10% increase in EhGSH, the odds of prevalent AF was 30% higher (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.1-1.7; P = .02) and 90% higher (OR 1.9; 95% CI 1.3-2.7; P = .004) when the median was used as a cutoff. The EhGSH level above the median was more predictive of chronic AF (OR 4.0; 95% CI 1.3-12.9; P = .01) than of paroxysmal AF (OR 1.7; 95% CI 1.1-2.7; P = .03). Each 10% increase in EhGSH level was associated with a 40% increase in the risk of incident AF (hazard ratio 1.4; 95% CI 1.1-1.7; P = .01). CONCLUSION: Increased OS measured by the redox potentials of glutathione is associated with prevalent and incident AF. Therapies that modulate OS need to be investigated to treat and prevent AF.

Progenitor Cells and Clinical Outcomes in Patients With Heart Failure.

BACKGROUND: Endogenous regenerative capacity, assessed as circulating progenitor cell (PC) numbers, is an independent predictor of adverse outcomes in patients with cardiovascular disease. However, their predictive role in heart failure (HF) remains controversial. We assessed the relationship between the number of circulating PCs and the pathogenesis and severity of HF and their impact on incident HF events. METHODS AND RESULTS: We recruited 2049 adults of which 651 had HF diagnosis. PCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34, CD133, vascular endothelial growth factor receptor-2, and chemokine (C-X-C motif) receptor 4 epitopes. PC subsets were lower in number in HF and after adjustment for clinical characteristics in multivariable analyses, a low CD34+ and CD34+/CXCR+ cell count remained independently associated with a diagnosis of HF (P<0.01). PC levels were not significantly different in reduced versus preserved ejection fraction patients. In 514 subjects with HF, there were 98 (19.1%) all-cause deaths during a 2.2±1.5-year follow-up. In a Cox regression model adjusting for clinical variables, hematopoietic-enriched PCs (CD34+, CD34+/CD133+, and CD34+/CXCR4+) were independent predictors of all-cause death (hazard ratio 2.0, 1.6, 1.6-fold higher mortality, respectively; P<0.03) among HF patients. Endothelial-enriched PCs (CD34+/VEGF+) were independent predictors of mortality in patients with HF with preserved ejection fraction only (hazard ratio, 5.0; P=0.001). CONCLUSIONS: PC levels are lower in patients with HF, and lower PC counts are strongly and independently predictive of mortality. Strategies to increase PCs and exogenous stem cell therapies designed to improve regenerative capacity in HF, especially, in HF with preserved ejection fraction, need to be further explored.

An Aggregate Biomarker Risk Score Predicts High Risk of Near-Term Myocardial Infarction and Death: Findings From BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes).

BACKGROUND: In a previous study, we found that a biomarker risk score (BRS) comprised of C-reactive protein, fibrin-degradation products, and heat shock protein-70 predicts risk of myocardial infarction and death in coronary artery disease patients. We sought to: (1) validate the BRS in the independent BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) cohort, (2) investigate whether 1 year of intensive medical therapy is associated with improved BRS, and (3) elucidate whether an altered BRS parallels altered risk. METHODS AND RESULTS: Two thousand thirty-two subjects with coronary artery disease were followed for 5.3±1.1 years for cardiovascular events. Biomarkers were measured at baseline and retested in 1304 subjects at 1 year. BRS was determined as the biomarker number above previously defined cut-off values (C-reactive protein >3 mg/L, heat shock protein-70 >0.313 ng/mL, and fibrin-degradation products >1 µg/mL). After adjustment for covariates, those with a BRS of 3 had a 4-fold increased risk of all-cause death and a 6.8-fold increased risk of cardiac death compared with those with a BRS of 0 (95% CI, 2.9-16.0; P<0.0001). All individual biomarkers decreased by 1 year, with ≈80% of patients decreasing their BRS. BRS recalibrated at 1 year also predicted risk. Those with 1-year BRS of 2 to 3 had a 4-year mortality rate of 21.1% versus 7.4% for those with BRS of 0 to 1 (P<0.0001). CONCLUSIONS: Our results validate the ability of the BRS to identify coronary artery disease patients at very high near-term risk of myocardial infarction/death. After 1 year of intensive medical therapy, the BRS decreased significantly, and the reclassified BRS continued to track with risk. Our results suggest that repeated BRS measurements might be used to assess risk and recalibrate therapy.

Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes.

BACKGROUND AND AIMS: Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation associated with atherosclerosis. Whether suPAR levels are associated with prevalent peripheral arterial disease (PAD) and its adverse outcomes remains unknown and is the aim of the study. METHODS: SuPAR levels were measured in 5810 patients (mean age 63 years, 63% male, 77% with obstructive coronary artery disease [CAD]) undergoing cardiac catheterization. The presence of PAD (n = 967, 17%) was classified as carotid (36%), lower/upper extremities (30%), aortic (15%) and multisite disease (19%). Multivariable logistic and Cox regression models were used to determine independent predictors of prevalent PAD and outcomes including all-cause death, cardiovascular death and PAD-related events after adjustment for age, gender, race, body mass index, smoking, diabetes, hypertension, hyperlipidemia, renal function, heart failure history, and obstructive CAD. RESULTS: Plasma suPAR levels were 22.5% (p < 0.001) higher in patients with PAD compared to those without PAD. Plasma suPAR was higher in patients with more extensive PAD (≥2 compared to single site) p < 0.001. After multivariable adjustment, suPAR was associated with prevalent PAD; odds ratio (OR) for highest compared to lowest tertile of 2.0, 95% CI (1.6-2.5) p < 0.001. In Cox survival analyses adjusted for clinical characteristics and medication regimen, suPAR (in the highest vs. lowest tertile) remained an independent predictor of all-cause death [HR 3.1, 95% CI (1.9-5.3)], cardiovascular death [HR 3.5, 95% CI (1.8-7.0)] and PAD-related events [HR = 1.8, 95% CI (1.3-2.6) p < 0.001 for all]. CONCLUSIONS: Plasma suPAR level is predictive of prevalent PAD and of incident cardiovascular and PAD-related events. Whether SuPAR measurement can help screen, risk stratify, or monitor therapeutic responses in PAD requires further investigation.

Effective Information Extraction Framework for Heterogeneous Clinical Reports Using Online Machine Learning and Controlled Vocabularies.

BACKGROUND: Extracting structured data from narrated medical reports is challenged by the complexity of heterogeneous structures and vocabularies and often requires significant manual effort. Traditional machine-based approaches lack the capability to take user feedbacks for improving the extraction algorithm in real time. OBJECTIVE: Our goal was to provide a generic information extraction framework that can support diverse clinical reports and enables a dynamic interaction between a human and a machine that produces highly accurate results. METHODS: A clinical information extraction system IDEAL-X has been built on top of online machine learning. It processes one document at a time, and user interactions are recorded as feedbacks to update the learning model in real time. The updated model is used to predict values for extraction in subsequent documents. Once prediction accuracy reaches a user-acceptable threshold, the remaining documents may be batch processed. A customizable controlled vocabulary may be used to support extraction. RESULTS: Three datasets were used for experiments based on report styles: 100 cardiac catheterization procedure reports, 100 coronary angiographic reports, and 100 integrated reports-each combines history and physical report, discharge summary, outpatient clinic notes, outpatient clinic letter, and inpatient discharge medication report. Data extraction was performed by 3 methods: online machine learning, controlled vocabularies, and a combination of these. The system delivers results with F1 scores greater than 95%. CONCLUSIONS: IDEAL-X adopts a unique online machine learning-based approach combined with controlled vocabularies to support data extraction for clinical reports. The system can quickly learn and improve, thus it is highly adaptable.

Bioactive Lipids and Circulating Progenitor Cells in Patients with Cardiovascular Disease.

Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry. CPCs were assessed using flow cytometry. S1P levels correlated with the numbers of CD34+, CD34+/CD133+, and CD34+/CXCR4+ CPCs even after adjustment for potential confounding factors. However, no significant correlation was observed between C1P levels and CPC count. Plasma levels of S1P correlated with the number of CPCs in patients with coronary artery disease, suggesting an important mechanistic role for S1P in stem cell mobilization. The therapeutic effects of adjunctive S1P therapy to mobilize endogenous stem cells need to be investigated. Stem Cells Translational Medicine 2017;6:731-735.

Age and Human Regenerative Capacity Impact of Cardiovascular Risk Factors.

RATIONALE: We investigated aging of human endogenous reparative capacity and aimed to clarify whether it is affected by presence of cardiovascular disease or its risk factors (RFs). OBJECTIVE: Circulating progenitor cell (PC) levels reflect endogenous regenerative potential. The effect on PC of healthy aging compared with aging with RFs or cardiovascular disease (CVD) is unknown. We examined whether exposure to RF and CVD leads to an accelerated decline in circulating PC with increasing age. METHODS AND RESULTS: In 2792 adult subjects, 498 were free of RFs (smoking, diabetes mellitus, hypertension, or hyperlipidemia), 1036 subjects had 1 to 2 RF, and 1253 had ≥3 RFs or CVD. PC were enumerated by flow cytometry as CD45(med+) mononuclear cells expressing CD34 and subsets coexpressing CD133, CXCR4, and vascular endothelial growth factor receptor-2 epitopes. Younger age, male sex, and larger body size correlated with higher PC counts (P<0.01). After multivariable adjustment, both age and RF categories were independently associated with PC counts (P<0.05), with lower PC counts in older subjects and those with higher RF burden or CVD. PC counts remained unchanged with increasing age in healthy individuals. There were significant interactions between age and RF categories (P≤0.005), such that for younger subjects (<40 years), RFs were associated with increased PC counts, whereas for older subjects (>60 years), RFs and CVD were associated with lower PC counts. CONCLUSIONS: Circulating PC levels do not decline with healthy aging; RF exposure at a younger age stimulates PC mobilization, whereas continued exposure is associated with lower PC levels in later life. Over the lifespan, exposure to RFs and CVD is associated with an initial stimulation and subsequent decline in circulating PC levels, which reflect endogenous regenerative capacity.