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Patients with type 2 diabetes mellitus are at increased risk for macrovascular disease complications. Hyperglycemia and atherosclerotic disease clearly are associated, and biologic intermediates mediated by hyperglycemia exist. Our understanding of the pathobiology linking hyperglycemia and atherosclerotic disease continues to evolve. Modulation of the advanced glycation end product (AGE) receptor for AGE (RAGE)/soluble RAGE (sRAGE) system, the thromboxane receptor, and C-peptide comprise just a few of the plausible links between dysglycemia and atherosclerosis. It seems intuitive, therefore, that therapeutic management of blood glucose in patients with diabetes should reduce macrovascular disease and related deaths. However, studies of glucose-lowering therapies performed to date yield qualitatively and quantitatively different results. No definitive proof of the concept is yet available, although it remains probable, with investigations presently under way. Numerous interventions extending beyond glucose control, including lifestyle modification, pharmacologic therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), aspirin, and angiotensin-converting enzyme inhibitors, as well as aggressive blood pressure control independent of blood pressure levels, have proved to be of cardiovascular benefit in the high-risk population of patients with diabetes. Thus, all of these interventions should be used in addition to glucose management in all patients with diabetes who are at increased risk for cardiovascular disease. [Copyright &y& Elsevier]

Patients who have diabetes mellitus have 2 times the incidence of an acute coronary syndrome (ACS) and 2 times the mortality rate after ACS compared with patients who do not have diabetes. Poor patient understanding of diabetes is believed to impede appropriate self-management, thus accelerating cardiovascular complications. We investigated the relation between patients'' diabetes-related knowledge (DRK) and measurements of risk factor control and cardiac outcomes. Two hundred patients who had diabetes mellitus and ACS and were admitted to a university hospital were enrolled over a 9-month period. At enrollment, clinical and demographic data were recorded, and each patient completed a previously validated DRK assessment. Clinical outcomes data were obtained 6 months after enrollment. Years of education and DRK assessment score were moderately correlated (r = 0.496, p <0.0001). Glycosylated hemoglobin, low-density lipoprotein cholesterol, and body mass index showed no correlation with DRK assessment score (r = −0.045, −0.005, and 0.175, respectively), even after multivariable adjustment for differences in age, race, insulin requirement, duration of diabetes, and years of education. Rates of 6-month death (6.2% vs 9.7%) and death or myocardial infarction (15.5% vs 19.4%) were not significantly different between groups of patients stratified by DRK assessment scores (high vs low scoring groups). Thus, among patients who have diabetes and ACS, there is a moderate correlation between years of education and DRK. We found no correlation between DRK and measurements of risk factor control or 6-month clinical outcomes. New strategies must be developed to translate understanding of disease into better risk factor modification among patients who have diabetes and ACS. [Copyright &y& Elsevier]

Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probabilitybased, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94,95% CI 0.78 to 1.13, Pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (Pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target. [ABSTRACT FROM AUTHOR]

Intensive statin therapy is a central component of secondary prevention after acute myocardial infarction (AMI), particularly among high-risk patients, such as those with diabetes mellitus (DM). However, the frequency and predictors of intensive statin therapy use after AMI among patients withDMhave not been described. We examined patterns of intensive statin therapy use (defined as a statin with expected low-density lipoprotein cholesterol lowering of >50%) at discharge among patientswithAMIwithknownDMenrolled in a 24-siteUSregistry. Predictors of intensive statin therapy use were evaluated using multivariable hierarchical Poisson regression models. Among 1,300 patients with DM after AMI, 22% were prescribed intensive statin therapy at hospital discharge. Inmultivariablemodels, ST-elevationAMI (risk ratio [RR] 1.48, 95% confidence interval [CI] 1.29 to 1.70), insurance for medications (RR 1.28, 95% CI 1.00 to 1.63), and higher low-density lipoprotein cholesterol levels (RR1.05 per 1mg/dl, 95%CI 1.02 to 1.07) were independent predictors of intensive statin therapy, whereas higher Global Registry of Acute Coronary Events scores were associated with lower rates of intensive statin therapy (RR0.94 per 10 points, 95%CI 0.91 to 0.98). In conclusion, only 1 in 5 patients withDM was prescribed intensive statin therapy at discharge after an AMI. Predictors of intensive statin therapy use suggest important opportunities to improve quality of care in this patient population. [ABSTRACT FROM AUTHOR]

Women with angina pectoris and abnormal stress test findings commonly have no epicardial coronary artery disease (CAD) at catheterization. The aim of the present study was to develop a risk score to predict obstructive CAD in such patients. Data were analyzed from 337 consecutive women with angina pectoris and abnormal stress test findings who underwent cardiac catheterization at our center from 2003 to 2007. Forward selection multivariate logistic regression analysis was used to identify the independent predictors of CAD, defined by ‡50% diameter stenosis in ‡1 epicardial coronary artery. The independent predictors included age ‡55 years (odds ratio 2.3, 95% confidence interval 1.3 to 4.0), body mass index <30 kg/m2 (odds ratio 1.9, 95% confidence interval 1.1 to 3.1), smoking (odds ratio 2.6, 95% confidence interval 1.4 to 4.8), low high-density lipoprotein cholesterol (odds ratio 2.9, 95% confidence interval 1.5 to 5.5), family history of premature CAD (odds ratio 2.4, 95% confidence interval 1.0 to 5.7), lateral abnormality on stress imaging (odds ratio 2.8, 95% confidence interval 1.5 to 5.5), and exercise capacity <5 metabolic equivalents (odds ratio 2.4, 95% confidence interval 1.1 to 5.6). Assigning each variable 1 point summed to constitute a risk score, a graded association between the score and prevalent CAD (ptrend <0.001). The risk score demonstrated good discrimination with a cross-validated c-statistic of 0.745 (95% confidence interval 0.70 to 0.79), and an optimized cutpoint of a score of £2 included 62% of the subjects and had a negative predictive value of 80%. In conclusion, a simple clinical risk score of 7 characteristics can help differentiate those more or less likely to have CAD among women with angina pectoris and abnormal stress test findings. This tool, if validated, could help to guide testing strategies in women with angina pectoris. [ABSTRACT FROM AUTHOR]

The Fick principle (cardiac output [Qc] = oxygen uptake [Vo 2]/arteriovenous oxygen difference) can be used to calculate Qc, with VO2 frequently estimated by derived equations. To compare the accuracy of measured versus estimated VO2, data were analyzed from 2 studies in which VO2 at rest was measured using the Douglas bag technique. One study comprised adults with diabetes, and the other was an exercise study of healthy adults. VO2 at rest was estimated as VO2 (ml/min) = 125 ml/min/m2 × body surface area (m2), with sensitivity analyses evaluating 2 other commonly used equations. Mean absolute difference (milliliters per minute) and ordinary least products regression were used to assess agreement between measured and estimated VO2. Overall, mean measured versus estimated VO2 differed significantly (307.2 ± 75.2 vs 259.9 ± 36.7 ml/min, p <0.0001), with a mean absolute difference of 52.9 ± 43.2 ml/min (p <0.0001); 20% of the estimates differed by >25% from the measured VO2. Mean absolute difference increased from 36.7 ml/min in the lowest body mass index group (<25 kg/m2) to 91.7 ml/min in the highest group (≥40 kg/m2) (p for trend = 0.001) and was significantly higher in men than in women (65.6 vs 33.9 ml/min, p = 0.001); error was similar by median-split age (p = 0.65) and race (p = 0.34). Similar results were obtained when evaluating each of the other 2 estimating equations. Estimation of VO2 at rest is inaccurate, especially in men and with increasing adiposity. In conclusion, when clinical hemodynamic assessment is performed, VO2 should be measured, not estimated. [ABSTRACT FROM AUTHOR]

This randomized, double-blind, parallel trial assessed the influence of pomegranate juice consumption on anterior and posterior carotid intima–media thickness (CIMT) progression rates in subjects at moderate risk for coronary heart disease. Subjects were men (45 to 74 years old) and women (55 to 74 years old) with ≥1 major coronary heart disease risk factor and baseline posterior wall CIMT 0.7 to 2.0 mm, without significant stenosis. Participants consumed 240 ml/day of pomegranate juice (n = 146) or a control beverage (n = 143) for up to 18 months. No significant difference in overall CIMT progression rate was observed between pomegranate juice and control treatments. In exploratory analyses, in subjects in the most adverse tertiles for baseline serum lipid peroxides, triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, TGs/HDL cholesterol, total cholesterol/HDL cholesterol, and apolipoprotein-B100, those in the pomegranate juice group had significantly less anterior wall and/or composite CIMT progression versus control subjects. In conclusion, these results suggest that in subjects at moderate coronary heart disease risk, pomegranate juice consumption had no significant effect on overall CIMT progression rate but may have slowed CIMT progression in subjects with increased oxidative stress and disturbances in the TG-rich lipoprotein/HDL axis. [Copyright &y& Elsevier]

The relations between renal function and circulating B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-pro-BNP) in the general population have not been fully elucidated. A total of 2,784 subjects from the Dallas Heart Study, a multiethnic population-based sample of Dallas County, Texas, residents, was studied. Detailed cardiac phenotyping, including magnetic resonance imaging and electron beam computed tomography, as well as measurements of NT-pro-BNP and BNP, were performed. Associations between estimated glomerular filtration rate (eGFR) and both NT-pro-BNP and BNP were evaluated using multivariable statistical analysis techniques. Median eGFR in this young, predominantly healthy population was 97 ml/min/1.73 m 2 (interquartile range 84 to 112). Natriuretic peptide levels were not associated with renal function over the normal range of eGFR. Below a threshold eGFR of 90 ml/min/1.73 m 2 , both NT-pro-BNP and BNP increased in an exponential fashion with decreasing eGFR. These associations remained significant after adjustment for multiple potential confounders (p <0.001 for all). For eGFR <90 ml/min/1.73 m 2 , the relative increase in NT-pro-BNP was twice as great as that for BNP for a given decrease in eGFR. In conclusion, a threshold effect regarding the association between renal function and natriuretic peptides was shown. With eGFR <90 ml/min/1.73 m 2 , both NT-pro-BNP and BNP were inversely and independently associated with renal function, with a greater magnitude of association with renal impairment noted for NT-pro-BNP. [Copyright &y& Elsevier]

Family history of myocardial infarction (FHMI) is an independent risk factor for cardiovascular (CV) events but may be more informative in certain subgroups. The association between FHMI and the presence of coronary artery calcium (CAC) was examined in various age and risk factor groups in the Dallas Heart Study (DHS), a population-based probability sample of subjects aged 30 to 65 years. Analyses were stratified by age (with the young group composed of men aged <45 years and women aged <55 years) and by the presence of 0, 1, 2, or >2 CV risk factors. In the overall cohort of 2,743 subjects, FHMI was an independent predictor of CAC (adjusted odds ratio 1.3, 95% confidence interval 1.1 to 1.7), attributable to an independent association between FHMI and CAC in the young group (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1) that was not evident in the older subset (adjusted odds ratio 1.2, 95% confidence interval 0.91 to 1.6, interaction p = 0.02). In the young cohort, the association between FHMI and CAC was particularly robust in those with ≥2 risk factors (FHMI–by–risk factor interaction p = 0.04). In older subjects, FHMI was not associated with CAC for any risk factor category (p >0.05 for each). In conclusion, this study suggests that FHMI is a more important predictor of atherosclerosis in young compared with older adults and, among the young, in those with multiple CV risk factors. [Copyright &y& Elsevier]

Circulating osteoprotegerin (OPG) has been shown to be elevated in patients with vascular disease. The role of OPG as a biomarker for atherosclerosis in a large, unselected population is not well known. Plasma OPG levels were measured in 3,386 subjects in the Dallas Heart Study, a multiethnic, population-based probability sample of adults aged 30 to 65 years. Coronary artery calcium (CAC) was measured by electron beam computed tomography. Aortic plaque was assessed by magnetic resonance imaging. Multivariable logistic regression was used to assess associations among OPG, cardiovascular risk factors, CAC, and aortic plaque. Age, female gender, black race, smoking, personal and family history of coronary artery disease (CAD), diabetes mellitus, hyperlipidemia, CAC, and aortic plaque were significantly associated with higher plasma OPG levels (p <0.01) in univariable analyses. The prevalence of CAC and aortic plaque increased across OPG quartiles (p <0.001 for each). An OPG level in the fourth quartile was independently associated with CAC (RR 1.39, 95% confidence interval 1.01 to 1.93) and aortic plaque (RR 1.42, 95% confidence interval 1.09 to 1.86) after adjustment for age, gender, smoking, diabetes, hyperlipidemia, and family history of premature CAD. In conclusion, plasma OPG is independently associated with CAC and aortic plaque in an unselected population, suggesting it may be a novel biomarker for atherosclerosis in humans. [Copyright &y& Elsevier]

Patients with left bundle branch block (LBBB) and concomitant coronary artery disease (CAD) have a worse prognosis than those with LBBB without CAD. In addition, subjects with CAD and concomitant LBBB have a higher cardiovascular mortality than those with a similar extent of CAD but without LBBB. Because the presence of LBBB makes the noninvasive identification of CAD problematic, patients with LBBB often are referred for coronary angiography to assess the presence and severity of CAD. To determine the clinical and demographic variables that might help identify those with CAD, we analyzed data from 336 consecutive patients with LBBB referred for coronary angiography. Of the 336, 54% had CAD. In conclusion, those with CAD were likely to be older, Caucasian, and men; they were more likely to have angina pectoris, myocardial infarction, and diabetes mellitus; and they were more likely to have a left ventricular ejection fraction <0.50. In contrast, patients with heart failure were less likely to have CAD. [Copyright &y& Elsevier]

Elevated plasma levels of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT–pro-BNP) are seen in the setting of cardiac ischemia and are associated with adverse outcomes in patients with coronary artery disease. The mechanisms leading to natriuretic peptide elevation in patients with coronary artery disease, including the contribution of coronary atherosclerosis itself, have not been fully elucidated. Measurement of NT–pro-BNP, electron beam computed tomography, and cardiac magnetic resonance imaging were performed in 2,445 subjects from the Dallas Heart Study who were free of heart failure and renal insufficiency. Electron beam computed tomography–determined coronary artery calcium scores were categorized as none (<10), mild (≥10 to <100), moderate (≥100 to <400), and severe (≥400). NT–pro-BNP levels increased significantly across increasing coronary artery calcium score categories (p <0.0001 for trend). In multivariate models adjusted for age, gender, race, body mass index, hypertension, history of myocardial infarction, angina, angiotensin-converting enzyme inhibitor use, β-blocker use, left ventricular (LV) ejection fraction, and LV mass, higher coronary artery calcium scores remained independently associated with higher log NT–pro-BNP levels (p = 0.03). This association persisted in similar models excluding patients with low LV ejection fractions, LV hypertrophy, angina pectoris, and a history of myocardial infarction. In conclusion, these findings support the hypothesis that coronary atherosclerosis may directly influence the activation of the cardiac neurohormonal system. [Copyright &y& Elsevier]

Although the presence of coronary artery calcium (CAC) has been associated with the prevalence and incidence of coronary heart disease (CHD), it is unclear if this association has a threshold or a continuous relation. The aim of this research was to explore the relation between CAC, as detected by electron beam tomography (EBT), and CHD in a cross-sectional study of women and men who presented to a single center for elective screening with EBT from 1995 to 1998. Of 17,967 participants, patients with CHD had higher CAC levels than those without CHD. Using subjects without CAC as the referent group, the odds ratios for prevalent CHD increased significantly across increasing quartiles of CAC in the overall population and in both genders. In a subset of the population, after adjusting for CHD risk factors, CAC scores in the fourth quartile were associated with an odds ratio of 33.8 (p <0.001) for prevalent CHD. Among patients with and without CHD, men were more likely than women to have detectable CAC (58.1% vs 28.3% and 96.1% vs 68.9% respectively, p <0.001 for each); the prevalence of detectable CAC increased with age and was higher in men than in women. There was an increased risk for prevalent CHD at all levels of CAC >0, with the greatest increase in risk occurring in patients with CAC scores >95. These observations support the potential of EBT as a sensitive test for detection of CHD. [ABSTRACT FROM AUTHOR]

For patients undergoing nonurgent coronary stent implantation, blockade of the glycoprotein IIb/IIIa receptor with eptifibatide reduces the incidence of ischemic complications. We evaluated the interaction of eptifibatide with diabetes in patients who underwent this procedure by analyzing the 1-year outcomes of those enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial (466 diabetic and 1,595 nondiabetic patients). At 1 year, the composite end point of death, myocardial infarction (MI), or target vessel revascuarlization (TVR) was higher in diabetic patients (24.5% vs 18.4%; p = 0.008). At 1 year, eptifibatide had a similar effect on the composite end point of death, MI, or TVR in diabetic (hazards ratio [HR] 0.71, 95% confidence interval [CI] 0.49 to 1.04) and nondiabetic patients (HR 0.80, 95% CI 0.63 to 0.99). A similar treatment effect was also seen on death or MI in both groups. The 1-year mortality rate for diabetic patients assigned to placebo was 3.5% versus 1.3% for patients receiving eptifibatide (HR 0.37, 95% CI 0.10 to 1.41); the latter rate was similar to the mortality rate of 1.4% for nondiabetic patients in the eptifibatide group. However, eptifibatide did not have a significant effect on TVR in diabetic patients (HR 0.90, 95% CI 0.57 to 1.41). Our data suggest that treatment with eptifibatide is associated with a similar relative reduction in adverse ischemic complications in diabetic and nondiabetic patients undergoing coronary stent implantation. There is no evidence of a statistical interaction in the treatment effect of eptifibatide between patients with and without diabetes. [Copyright &y& Elsevier]

In patients who have ST-segment elevation myocardial infarction (STEMI), a patent infarct-related artery on the initial angiogram is associated with improved clinical outcomes, including decreased mortality. The present study assessed the influence of administering aspirin, β blockers, statins, and angiotensin-converting enzyme inhibitors before STEMI on infarct-related artery patency. Our data demonstrate that patients who have STEMI and receive these medications on an outpatient basis before the event have a higher likelihood of having a patent infarct-related artery compared with patients who do not receive these medications. Further, our data demonstrate a graded association according to the number of such medications being administered: the likelihood of a patent infarct-related artery increased to >50% as the number of these medications increased. [Copyright &y& Elsevier]

The baseline characteristics, complications, and survival of 489 black and 6,890 non-black patients with acute coronary syndromes were studied. Important racial differences were observed in demographic features, atherosclerosis risk factors, and treatment strategies; however, despite these differences, no independent difference was observed in clinical outcomes according to race. The 1-year mortality rate was 2.9% for black patients and 2.5% for non-black patients (p = 0.93). [Copyright &y& Elsevier]

To determine the effect of glucose-insulin-potassium infusion on circulating levels of free fatty acids in the setting of contemporary management of ST-elevation myocardial infarction, we randomly assigned 20 patients who were undergoing primary angioplasty to glucose-insulin-potassium infusion or to standard care. Treatment with glucose-insulin-potassium was associated with significantly lower levels of free fatty acid after 24 hours compared with standard care. [Copyright &y& Elsevier]

Selected glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have cardioprotective effects in patients with type 2 diabetes mellitus (T2D) and elevated cardiovascular risk. Prescription and consistent use of these medications are essential to realizing their benefits. In a nationwide deidentified United States administrative claims database of adults with T2D, the prescription practices of GLP-1RAs and SGLT-2i were evaluated across guideline-directed co-morbidity indications from 2018 to 2020. The monthly fill rates were assessed for 12 months after the initiation of therapy by calculating the proportion of days with consistent medication use. Of 587,657 subjects with T2D, 80,196 (13.6%) were prescribed GLP-1RAs and 68,149 (11.5%) SGLT-2i from 2018 to 2020, representing 12.9% and 11.6% of patients with indications for each medication, respectively. In new initiators, 1-year fill rate was 52.5% for GLP-1RAs and 52.9% for SGLT-2i, which was higher for patients with commercial insurance than those with Medicare Advantage plans for both GLP-1RAs (59.3% vs 51.0%, p <0.001) and SGLT-2i (63.4% vs 50.3%, p <0.001). After adjusting for co-morbidities, there were higher rates of prescription fills for patients with commercial insurance (odds ratio 1.17, 95% confidence interval 1.06 to 1.29 for GLP-1RAs, and 1.59 [1.42 to 1.77] for SGLT-2i); and higher income (odds ratio 1.09 [1.06 to 1.12] for GLP-1RAs, and 1.06 [1.03 to 1.1] for SGLT-2i). From 2018 to 2020, the use of GLP-1RAs and SGLT-2i remained limited to fewer than 1 in 8 patients with T2D and indications, with 1-year fill rates around 50%. The low and inconsistent use of these medications compromises their longitudinal health outcome benefits in a period of expanding indications for their use., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The thermodilution (TD) method is routinely used for the estimation of cardiac output (Q̇ C ). However, its accuracy, compared with the gold-standard Fick method, where systemic oxygen uptake (V̇O 2 ) is directly measured, and Q̇ C calculated from V̇O 2 and the arterio-venous oxygen difference ("direct" Fick), has not been well validated. The present study determined the agreement between TD and Fick methods in consecutive patients who underwent pulmonary artery catheterization for a broad range of clinical conditions. This is a subanalysis of a previous study comparing the indirect versus Fick method based on a prospective, consecutive patient registry of 253 patients who underwent pulmonary artery catheterization for clinical indications at a single center between 1999 and 2005. We included patients that had an estimation of Q̇ C both by the Fick method using measured V̇O 2 by exhaled gas analyses from timed Douglas bag collections and by TD. Cardiac index was classified as low when ≤2.2 L/min/m 2 or normal when >2.2 L/min/m 2 . The median (25th, 75th percentile) age of the cohort was 59 (50,67) years, and 50% were female. A total of 43.5% had normal left ventricular function by ventriculography, and 25.7% had ischemic heart disease. Median overall Fick and TD Q̇ C were 4.4 (3.5, 5.5) and 4.3 (3.7, 5.2) L/min, respectively (p = 0.04). The median absolute percent error between Fick and TD Q̇ C was 17.5 (7.7, 28.4)%, with a typical error of 0.88 L/min (95% confidence interval [CI] 0.82 to 0.95). Median absolute percent error was comparable in the low (n = 118) and normal Q̇ CI (n = 135) groups (16.9% vs 18.9%, respectively, p = 0.88). typical error was 0.3 (95% CI 0.27 to 0.33) and 0.49 (95% CI 0.45 to 0.55) L/min/m 2 in that comparison. Percent error >25% between Fick and TD Q̇ C was observed in over 30% of patients. Overall, Fick and TD Q̇ C modestly correlated (R s  = 0.64, p <0.001), with a nondirectional error introduced by TD Q̇ C [mean bias of 0.21 (-2.2, 2.7) L/min]. There was poor agreement between TD and the gold-standard Fick method, highlighting the limitations of making clinical decisions based on TD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dipeptidyl peptidase-4 inhibitors (DPP-4i) are one of the most widely used antihyperglycemic therapeutic classes in type 2 diabetes mellitus management. In April 2016 and August 2017, the US Food and Drug Administration (FDA) introduced sequential labelling requirements regarding heart failure risk related to DPP-4i. We explored longitudinal trends in prescription of DPP-4i before and after these FDA warnings in a multicenter health system. We identified all first-time prescriptions of DPP4i or their combinations across the Partners HealthCare system (Boston, MA) from October 2006 (FDA approval of first DPP-4i) to December 2018. Overall, 11,830 patients were newly prescribed DPP-4i during the study period. Primary care physicians (31.5%) were the most common prescribing specialty. Overall, 8.4%, 20.4%, and 11.6% had heart failure, atherosclerotic cardiovascular disease, and chronic kidney disease, respectively. Median number of background antihyperglycemic therapies was 2 [25th to 75th percentiles 1 to 2], commonly metformin (65.4%) and/or insulin (36.4%). The vast majority of prescriptions were sitagliptin (85.7%), followed by linagliptin (9.5%), saxagliptin (4.7%), and alogliptin (0.2%). Quarterly prescriptions rose gradually from 2006 to mid-2016, and have decreased consistently since then for each of the 4 DPP-4i. Declines in DPP-4i among high-risk groups and those initiated by endocrinologists were most pronounced. In conclusion, although DPP-4i remain a dominant oral antihyperglycemic therapy in clinical practice, new prescriptions have declined recently. These data may reflect relatively swift health system response to broad FDA safety communications regarding heart failure risk, which appeared to impact the entire DPP-4i class, including specific drugs that have not demonstrated any increased risk of heart failure., Competing Interests: Disclosures Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541), serves on advisory boards for Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, & Relypsa, and participates on clinical endpoint committees for studies sponsored by Novartis and the NIH. Dr. Singh reports no disclosures. Dr. Sharma has received support from Bayer-Canadian Cardiovascular Society, Alberta Innovates Health Solution, Bristol-Myers Squibb-Pfizer, Boehringer Ingelheim, Roche Diagnostics, and Takeda. Dr. Januzzi is supported in part by the Hutter Family Professorship; has received grant support from Abbott, Cleveland Heart Labs, Singulex, and Prevencio; has received consulting income from Roche Diagnostics, Critical Diagnostics, and Novartis; and has participated in clinical endpoint committees/data or safety monitoring boards for Novartis, Amgen, GE, Janssen, Pfizer, and Boehringer Ingelheim. Dr. Scirica reports research grants via Brigham and Women's Hospital from AstraZeneca, Eisai, Novartis, and Merck. Consulting fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Dr. Reddy's Laboratory, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Lexicon, Merck, NovoNordisk, Sanofi, St. Jude's Medical, and equity in Health [at] Scale. Dr. Butler has received research support from the NIH and European Union; and has been a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, Relypsa, Vifor Pharma, and ZS Pharma. Dr. Zannad reports personal fees from Janssen Research & Development LLC and Bayer during the conduct of the study; personal fees from AstraZeneca, Boehringer Ingelheim, LivaNova, GE Healthcare, Amgen, Novartis, Quantum Genomics, Cardior Pharmaceuticals, CardioRenal, CVCT, Merck, CVRx, Vifor Fresenius Medical Care Renal Pharma, NovoNordisk, and MundiPharma outside the submitted work; fees for serving on a steering committee or a safety and data monitoring board from Actelion, Amgen, Bayer, Boehringer Ingelheim, Boston Scientific, CVRx, GE Healthcare, Janssen Research & Development LLC, Novartis, and ResMed; and consulting fees from AstraZeneca, Cardior Pharmaceuticals, CardioRenal, Quantum Genomics, and Vifor Fresenius Medical Care Renal Pharma. Dr. McGuire reports honoraria for trial leadership from Astra Zeneca, Sanofi Aventis, Janssen, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Lexicon, Eisai, GlaxoSmithKline, Esperion, Lilly US; and honoraria for consulting for Astra Zeneca, Sanofi Aventis, Lilly US, Astra Zeneca, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Metavant, Applied Therapeutics. Dr. Cannon reports research grants from (all >10K) Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb (BMS), Daiichi Sankyo, Janssen, Merck; and consulting fees from Alnylam, Amarin, Amgen, Boehringer-Ingelheim, BMS, Eisai, Janssen, Kowa, Merck, Pfizer, Regeneron, and Sanofi. Dr. Bhatt discloses the following relationships - Advisory Board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, Takeda., (Copyright © 2020 Elsevier Inc. 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