Publications by authors named "Adam J Nelson"

97 Publications

Cardiovascular Safety of Degarelix versus Leuprolide in Patients with Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.

Circulation 2021 Aug 30. Epub 2021 Aug 30.

Department of Medicine, Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.

The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease (ASCVD) remains controversial. In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant ASCVD were randomized 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (MACE) (composite of death, myocardial infarction, or stroke) through 12 months. Due to slower than projected enrollment and fewer than projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From 3 May 2016 to 16 April 2020, a total of 545 patients from 113 sites across 12 countries were randomized. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease and 20.4% had metastatic disease. MACE occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) assigned to leuprolide (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.59-2.79; p=0.53). PRONOUNCE is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely due to smaller than planned number of participants and events and no difference in MACE at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. URL: https://clinicaltrials.gov Unique Identifier: NCT02663908.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.056810DOI Listing
August 2021

Dissemination of Transcatheter Aortic Valve Replacement in the United States.

J Am Coll Cardiol 2021 Aug;78(8):794-806

University of Colorado School of Medicine, Aurora, Colorado, USA.

Background: Societal guidelines and payor coverage decisions for transcatheter aortic valve replacement (TAVR) attempt to strike a balance between providing access and maintaining quality. The extent to which dissemination of TAVR has achieved these ideals remains unknown.

Objectives: This study sought to define patterns of TAVR dissemination in the United States and their influence on outcomes.

Methods: Using data from the TVT (Transcatheter Valvular Therapy) registry, this study identified TAVR sites from 2011 to 2018 and calculated drive-times from existing to new sites. In a contemporary cohort, this study compared site and patient characteristics by annual case volume and density of sites per million Medicare beneficiaries. Using hierarchical regression and Cox methods, this study determined the association between case volumes, site density, and changes in volume and density with patient risk profiles and outcomes.

Results: TAVR sites participating in the TVT registry increased from 198 to 556 from 2011 to 2018. Median drive-time from existing to new sites decreased from 403 minutes (interquartile range: 211-587 minutes) to 26 minutes (interquartile range: 17-48 minutes). In a contemporary cohort, higher site density was associated with lower procedural risk as well as with an increased hazard of 30-day risk-adjusted mortality (P = 0.017). Similarly, longitudinal increases in site density over time were associated with a higher hazard of 30-day (P = 0.011) and 1-year (P = 0.013) mortality.

Conclusions: TAVR has expanded significantly over time, but with regional clustering of sites. Although procedural risk is lower at higher density sites, these sites demonstrate an increased hazard of mortality. These findings suggest that the expansion of TAVR services in the United States may have had unintended consequences on procedural quality.
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http://dx.doi.org/10.1016/j.jacc.2021.06.028DOI Listing
August 2021

C-reactive protein levels and plaque regression with evolocumab: Insights from GLAGOV.

Am J Prev Cardiol 2020 Sep 6;3:100091. Epub 2020 Oct 6.

Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Melbourne, Australia.

Objective: On-treatment levels of high sensitivity C-reactive protein (hsCRP) in statin-treated patients predict plaque progression and the prospective risk of atherosclerotic cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors produce additional LDL-C lowering, reduce plaque burden and improve cardiovascular outcomes in statin-treated patients. It is unknown whether residual systemic inflammation attenuates their favorable effects on plaque burden.

Methods: GLAGOV compared the effects of treatment for 78 weeks with evolocumab or placebo on progression of coronary atherosclerosis in statin-treated patients with coronary artery disease.Clinical demographics, biochemistry and changes in both the burden (percentage atheroma volume (PAV), total atheroma volume (TAV), n ​= ​413) and composition (n ​= ​162) of coronary plaque were evaluated in evolocumab-treated patients according to baseline hsCRP strata (<1, 1-3, >3 ​mg/L).

Results: The study cohort comprised 413 evolocumab-treated patients (32% low [<1 ​mg/L], 41% intermediate [1-3 ​mg/L] and 27% high [>3 ​mg/L] baseline hsCRP levels). Patients in the highest hsCRP stratum were more likely to be female and had a higher prevalence of diabetes, hypertension, and the metabolic syndrome. LDL-C levels were similar across the groups, however participants with higher hsCRP levels had higher triglyceride and lower HDL-C levels at baseline. At follow-up, the change in PAV from baseline (-0.87% [low] vs. -0.84% [intermediate] vs. -1.22% [high], p ​= ​0.46) and the proportion of patients experiencing any degree of regression (65.9% vs. 63.5% vs. 63.1%, p ​= ​0.88) was similar across hsCRP strata and when evaluated by levels of achieved LDL-C. There were no serial differences in plaque composition by hsCRP strata.

Conclusion: The ability of evolocumab to induce regression in statin-treated patients is not attenuated by the presence of enhanced systemic inflammation. This underscores the potential benefits of intensive lipid lowering, even in the presence of heightened inflammatory states.
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http://dx.doi.org/10.1016/j.ajpc.2020.100091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315612PMC
September 2020

Incorporating SGLT2i and GLP-1RA for Cardiovascular and Kidney Disease Risk Reduction: Call for Action to the Cardiology Community.

Circulation 2021 Jul 6;144(1):74-84. Epub 2021 Jul 6.

Duke Clinical Research Institute, Durham, NC (A.J.N., N.J.P., J.B.G., R.D.L., H.A., L.A.K., E.C.O., M.R., L.W., C.B.G.).

Multiple sodium glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to impart significant cardiovascular and kidney benefits, but are underused in clinical practice. Both SGLT-2i and GLP-1RA were first studied as glucose-lowering drugs, which may have impeded uptake by cardiologists in the wake of proven cardiovascular efficacy. Their significant effect on cardiovascular and kidney outcomes, which are largely independent of glucose-lowering effects, must drive a broader use of these drugs. Cardiologists are 3 times more likely than endocrinologists to see patients with both type 2 diabetes and cardiovascular disease, thus they are ideally positioned to share responsibility for SGLT-2i and GLP-1RA treatment with primary care providers. In order to increase adoption, SGLT-2i and GLP-1RA must be reframed as primarily cardiovascular and kidney disease risk-reducing agents with a side effect of glucose-lowering. Coordinated and multifaceted interventions engaging clinicians, patients, payers, professional societies, and health systems must be implemented to incentivize the adoption of these medications as part of routine cardiovascular and kidney care. Greater use of SGLT-2i and GLP-1RA will improve outcomes for patients with type 2 diabetes at high risk for cardiovascular and kidney disease.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.053766DOI Listing
July 2021

Classification performance of clinical risk scoring in suspected acute coronary syndrome beyond a rule-out troponin profile.

Eur Heart J Acute Cardiovasc Care 2021 Jul 1. Epub 2021 Jul 1.

College of Medicine & Public Health, Flinders University, Sturt Road, Bedford Park, SA 5042, Australia.

Aims: High-sensitivity cardiac troponin strategies can provide risk stratification in patients with suspected acute coronary syndrome (ACS) in the emergency department (ED). This study evaluated whether clinical risk scoring improves the classification performance of a rule-out profile in suspected ACS.

Methods And Results: Patients presenting to ED with suspected ACS as part of the RAPID-TnT trial randomized to the intervention arm were included. Results ≥5 ng/L were available for all participants in this analysis. We evaluated the Thrombolysis In Myocardial Infarction (TIMI) risk score, History ECG Age Risk factors Troponin (HEART) score, and Emergency Department Assessment of Chest pain Score (EDACS) in addition to a rule-out profile based on the 0/1-h high-sensitivity cardiac troponin T protocol (<5 ng/L or ≤12 ng/L and a change of <3 ng/L at 1-h) using test performance parameters focusing on low-risk groups to identify the primary endpoint (TIMI ≤ 1, HEART ≤ 3, EDACS < 16). Primary endpoint was a composite of type 1/2 myocardial infarction (MI) at index presentation and all-cause mortality or type 1/2 MI at 30 days. A total of 3378 participants were enrolled between August 2015 and April 2019 of which 108 were ineligible/withdrew consent (intervention arm: n = 1638). Sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the rule-out profile was 94.4%, 76.8%, 99.6%, and 0.86, respectively with 72.9% identified as 'low-risk'. Adding the clinical risk scores did not improve the sensitivity, NPV, or AUC with significantly lower specificity and 'low-risk' classified participants.

Conclusions: Addition of clinical risk scores to rule-out profile did not demonstrate improved classification performance for identifying the composite of type 1/2 MI at index presentation and all-cause mortality or type 1/2 MI at 30 days.

Clinical Trials Registration: URL: https://www.anzctr.org.au. Reg. No. ACTRN12615001379505.
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http://dx.doi.org/10.1093/ehjacc/zuab040DOI Listing
July 2021

Late Outcomes of the RAPID-TnT Randomized Controlled Trial: 0/1-Hour High-Sensitivity Troponin T Protocol in Suspected ACS.

Circulation 2021 Jul 16;144(2):113-125. Epub 2021 May 16.

College of Medicine and Public Health, Flinders University of South Australia, Adelaide (K.L., A.B., A.S., A.C., E.K., E.M., J.K., D.P.C.).

Background: High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol.

Methods: We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to <5 ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals.

Results: Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632; unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 [14.2%]; 0/3-hour masked: 202/1632 [12.4%]; =0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 [11.2%]; 0/3-hour masked arm: 124/1486 [8.3%]; =0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 [5.0%] versus 0/3-hour: 62/1632 [3.8%]; hazard ratio, 1.32 [95% CI, 0.95-1.83]; =0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 [3.7%] versus 0/3-hour: 34/1486 [2.3%]; hazard ratio, 1.60 [95% CI, 1.05-2.46]; =0.030).

Conclusions: Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615001379505.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055009DOI Listing
July 2021

The SAMSON trial: using a placebo to improve medication tolerability.

Eur Heart J Cardiovasc Pharmacother 2021 May;7(3):e13

Duke Clinical Research Institute and the Division of Cardiology, Duke University Medical Center, Durham, NC, USA.

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http://dx.doi.org/10.1093/ehjcvp/pvab017DOI Listing
May 2021

Practical Application of Patient-Reported Health Status Measures for Transcatheter Valve Therapies: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry.

Circ Cardiovasc Qual Outcomes 2021 03 18;14(3):e007187. Epub 2021 Feb 18.

Department of Cardiovascular Medicine, Saint Luke's Mid America Heart Institute, Kansas City, MO (V.H., A.O.M., J.A.S., S.V.A.).

Background: Health status assessment is essential for documenting the benefit of transcatheter aortic valve replacement (TAVR) or transcatheter mitral valve repair on patients' symptoms, function, and quality of life. Health status can also be a powerful marker for subsequent clinical outcomes, but its prognostic importance around the time of both TAVR and transcatheter mitral valve repair has not been fully defined.

Methods: Among 73 699 patients who underwent transfemoral TAVR or transcatheter mitral valve repair between 2011 and 2018 (mean age, 81.9±7.0 years, 53% men, 92% TAVR), we constructed sequential models examining the association of health status (as assessed with the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score; KCCQ-OS) at baseline, 30 days, change from baseline to 30 days, and combinations of these assessments with death and heart failure (HF) hospitalization from 30 days to 1 year.

Results: Although higher baseline KCCQ-OS and 30-day KCCQ-OS scores were each associated with lower risk of death and HF hospitalization (in individual models and in a model including both measures), the 30-day KCCQ-OS was most predictive (death: hazard ratio, 0.89 per 5-point increase [95% CI, 0.89-0.90]; HF hospitalization: hazard ratio, 0.91 [95% CI, 0.90-0.91]). The 30-day KCCQ-OS also was most predictive when included in a separate model with change in KCCQ from baseline to 30 days. Similar findings were noted for the outcomes of death and of HF hospitalization, unadjusted and adjusted for patient factors. All interaction terms between procedure type and KCCQ were not significant, suggesting that health status provided similar prognostic information in both procedures.

Conclusions: The patient's assessment of their health status immediately before and 30 days after TAVR and transcatheter mitral valve repair is associated with subsequent risk of death and HF hospitalization, with the 30-day assessment being most strongly associated with outcomes. Our findings support the routine use of KCCQ data as a prognostic tool.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.007187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982132PMC
March 2021

The incremental value of angiographic features for predicting recurrent cardiovascular events: Insights from the Duke Databank for Cardiovascular Disease.

Atherosclerosis 2021 03 8;321:1-7. Epub 2021 Feb 8.

University of Texas Southwestern Medical Center, Dallas, TX, USA.

Background And Aims: Identifying patient subgroups with cardiovascular disease (CVD) at highest risk for recurrent events remains challenging. Angiographic features may provide incremental value in risk prediction beyond clinical characteristics.

Methods: We included all cardiac catheterization patients from the Duke Databank for Cardiovascular Disease with significant coronary artery disease (CAD; 07/01/2007-12/31/2012) and an outpatient follow-up visit with a primary care physician or cardiologist in the same health system within 3 months post-catheterization. Follow-up occurred for 3 years for the primary major adverse cardiovascular event endpoint (time to all-cause death, myocardial infarction [MI], or stroke). A multivariable model to predict recurrent events was developed based on clinical variables only, then adding angiographic variables from the catheterization. Next, we compared discrimination of clinical vs. clinical plus angiographic risk prediction models.

Results: Among 3366 patients with angiographically-defined CAD, 633 (19.2%) experienced cardiovascular events (death, MI, or stroke) within 3 years. A multivariable model including 18 baseline clinical factors and initial revascularization had modest ability to predict future atherosclerotic cardiovascular disease events (c-statistic = 0.716). Among angiographic predictors, number of diseased vessels, left main stenosis, left anterior descending stenosis, and the Duke CAD Index had the highest value for secondary risk prediction; however, the clinical plus angiographic model only slightly improved discrimination (c-statistic = 0.724; delta 0.008). The net benefit for angiographic features was also small, with a relative integrated discrimination improvement of 0.05 (95% confidence interval: 0.03-0.08).

Conclusions: The inclusion of coronary angiographic features added little incremental value in secondary risk prediction beyond clinical characteristics.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221430PMC
March 2021

Gaps in Evidence-Based Therapy Use in Insured Patients in the United States With Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease.

J Am Heart Assoc 2021 01 12;10(2):e016835. Epub 2021 Jan 12.

Duke Clinical Research Institute Duke University School of Medicine Durham NC.

Background Evidence-based therapies are generally underused for cardiovascular risk reduction; however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Methods and Results Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence-based therapies on, or covering, the index date ±30 days: high-intensity statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence-based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the sample, 24.7% were using a high-intensity statin, 53.1% were using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence-based therapies, and 37.4% were on none of them. Over a 12-month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence-based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients. Conclusions Alarming gaps exist in the contemporary use of evidence-based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.
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http://dx.doi.org/10.1161/JAHA.120.016835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955303PMC
January 2021

Can the Absence of Hypertension Refine the Risk Assessment of Older Adults for Future Cardiovascular Events?

Am J Cardiol 2021 03 9;142:83-90. Epub 2020 Dec 9.

University of Texas Southwestern Medical Center, Dallas Texas.

We sought to determine if the absence of hypertension in older adults can be used to identify those at lower risk of atherosclerotic cardiovascular disease (ASCVD). We identified participants ≥75 years old free of cardiovascular disease (CVD) in the National Institutes of Health Pooled Cohorts with and without hypertension. We assessed the association between systolic blood pressure (BP), diastolic BP, and cardiovascular events using multivariable modeling. The association between predicted ASCVD risk and observed events was compared. Of 2,667 adults aged ≥75 years, 67.9% had hypertension. Lower systolic BP correlated with lower CVD event rates. ASCVD predicted risk score and systolic BP were both independently associated with ASCVD event rates. Among adults with similar ASCVD predicted risk estimates, those without (vs with) hypertension had lower observed event rates across the predicted risk spectrum. The absence of hypertension may help refine the risk stratification of older adults, particularly those with intermediate predicted risk.
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http://dx.doi.org/10.1016/j.amjcard.2020.11.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221431PMC
March 2021

The role of intracoronary imaging in translational research.

Cardiovasc Diagn Ther 2020 Oct;10(5):1480-1507

Department of Cardiology, Central Adelaide Local Health Network, Adelaide, Australia.

Atherosclerotic cardiovascular disease is a key public health concern worldwide and leading cause of morbidity, mortality and health economic costs. Understanding atherosclerotic plaque microstructure in relation to molecular mechanisms that underpin its initiation and progression is needed to provide the best chance of combating this disease. Evolving vessel wall-based, endovascular coronary imaging modalities, including intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS), used in isolation or as hybrid modalities, have been advanced to allow comprehensive visualization of the pathological substrate of coronary atherosclerosis and accurately measure temporal changes in both the vessel wall and plaque characteristics. This has helped further our appreciation of the natural history of coronary artery disease (CAD) and the risk for major adverse cardiovascular events (MACE), evaluate the responsiveness to conventional and experimental therapeutic interventions, and assist in guiding percutaneous coronary intervention (PCI). Here we review the use of different imaging modalities for these purposes and the lessons they have provided thus far.
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http://dx.doi.org/10.21037/cdt-20-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666942PMC
October 2020

The fish-oil paradox.

Curr Opin Lipidol 2020 12;31(6):356-361

Duke Clinical Research Institute, Durham, North Carolina, USA.

Purpose Of Review: Increasing interest has focused on the potential cardioprotective effects of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the basis of findings from epidemiology and cohort studies. This review will summarize the findings of contemporary clinical trials of omega-3 fatty acids.

Recent Findings: Although a large clinical trial performed prior to the widespread use of statins demonstrated cardiovascular benefit with fish oils, subsequent studies have failed to reproduce this result. More recent studies have demonstrated a reduction in cardiovascular risk with administration of high-dose EPA, but not a carboxylic acid formulation containing both EPA and DHA or with lower doses of omega-3 fatty acids.

Summary: Administration of omega-3 fatty acids differing in either composition or dose produce variable effects on cardiovascular outcomes. This has implications for both the public health and pharmacological approach to cardiovascular prevention.
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http://dx.doi.org/10.1097/MOL.0000000000000712DOI Listing
December 2020

Representation of Older Adults in Cardiovascular Disease Trials Since the Inclusion Across the Lifespan Policy.

JAMA Intern Med 2020 11;180(11):1531-1533

Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.

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http://dx.doi.org/10.1001/jamainternmed.2020.2750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489390PMC
November 2020

Association Between Triglycerides and Residual Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease (From the Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D] Trial).

Am J Cardiol 2020 10 12;132:36-43. Epub 2020 Jul 12.

Duke Clinical Research Institute, Duke University, Durham, North Carolina. Electronic address:

Triglyceride (TG) levels encompass several lipoproteins that have been implicated in atherogenic pathways. Whether TG levels independently associate with cardiovascular disease both overall and, in particular among patients with established coronary artery disease (CAD) and type 2 diabetes (T2DM), remains controversial. Data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was used to evaluate patients with T2DM and CAD. Cox proportional hazards models were used to determine the association between TG levels and outcomes. Stepwise adjustment was performed for demographics, clinical factors, lipid profile and statin treatment. The primary composite outcome was time to CV death, myocardial infarction (MI), or stroke and secondary outcome was CV death. Among 2,307 patients with T2DM and CAD, the mean (±SD) TG levels were 181 (±136) with a median (Q1-Q3) 148mg/dL (104-219). Overall, 51% of patients had TG <150 mg/dL, 18% 150-199 mg/dL, 28% 200-499 mg/dL and 3% ≥500 mg/dL. Participants with elevated TG levels (≥150 mg/dL) were younger (61 vs 63 years, p <0.001), had higher BMI (32 vs 30 kg/m, p <0.001), more likely to have had prior MI (34.2 vs 30.1%, p = 0.033) and revascularization (25.8 vs 21.4%, p = 0.013), had lower HDL-C (34 vs 39 mg/dL, p <0.001) and higher HbA1c (8 vs 7%, p <0.001). In unadjusted analyses, baseline TG levels were linearly associated with both the primary composite and secondary outcomes. In fully adjusted analyses, every 50 mg/dL increase in TG level was associated with a 3.8% (HR 1.038, 95%CI 1.004-1.072, p <0.001) increase in the primary composite outcome and a 6.4% (HR 1.064 95%CI 1.018-1.113, p <0.001) increase in the secondary outcome. There was no interaction between TG and outcomes within key subgroups including female sex, additional non-coronary atherosclerotic disease, CKD or low LDL (<100 mg/dL). In conclusion, among patients with T2DM and CAD, elevated TG were independently associated with adverse cardiovascular outcomes, even after adjustment for clinical and simple biochemical covariates.
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http://dx.doi.org/10.1016/j.amjcard.2020.07.005DOI Listing
October 2020

Fluid structure interaction modelling of aortic valve stenosis: Effects of valve calcification on coronary artery flow and aortic root hemodynamics.

Comput Methods Programs Biomed 2020 Nov 8;196:105647. Epub 2020 Jul 8.

School of Mechanical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia.

Background And Objective: Coronary artery diseases and aortic valve stenosis are two of the main causes of mortality and morbidity worldwide. Stenosis of the aortic valve develops due to calcium deposition on the aortic valve leaflets during the cardiac cycle. Clinical investigations have demonstrated that aortic valve stenosis not only affects hemodynamic parameters inside the aortic root but also has a significant influence on the coronary artery hemodynamics and leads to the initiation of coronary artery disease. The aim of this study is to investigate the effect of calcification of the aortic valve on the variation of hemodynamic parameters in the aortic root and coronary arteries in order to find potential locations for initiation of the coronary stenoses.

Methods: Fluid structure interaction modelling methodology was used to simulate aortic valve hemodynamics in the presence of coronary artery flow. A 2-D model of the aortic valve leaflets was developed in ANSYS Fluent based on the available echocardiography images in literature. The k-ω SST turbulence model was utilised to model the turbulent flow downstream of the leaflets.

Results: The effects of calcification of the aortic valve on aortic root hemodynamics including transvalvular pressure gradient, valve orifice dimeter, vorticity magnitude in the sinuses and wall shear stress on the ventricularis and fibrosa layers of the leaflets were studied. Results revealed that the transvalvular pressure gradient increases from 792 Pa (∼ 6 mmHg) for a healthy aortic valve to 2885 Pa (∼ 22 mmHg) for a severely calcified one. Furthermore, the influence of the calcification of the aortic valve leaflets on the velocity profile and the wall shear stress in the coronary arteries was investigated and used for identification of potential locations of initiation of the coronary stenoses. Obtained results show that the maximum velocity inside the coronary arteries at early diastole decreases from 1 m/s for the healthy valve to 0.45 m/s for the severely calcified case.

Conclusions: Calcification significantly decreases the wall shear stress of the coronary arteries. This reduction in the wall shear stress can be a main reason for initiation of the coronary atherosclerosis process and eventually results in coronary stenoses.
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http://dx.doi.org/10.1016/j.cmpb.2020.105647DOI Listing
November 2020

Management of multivessel coronary artery disease in patients with non-ST-elevation myocardial infarction: a complex path to precision medicine.

Ther Adv Chronic Dis 2020 1;11:2040622320938527. Epub 2020 Jul 1.

Vascular Research Centre, Lifelong Health Theme, South Australian Health & Medical Research Institute, North Terrace, Adelaide, South Australia, 5000, Australia.

Recent analyses suggest the incidence of acute coronary syndrome is declining in high- and middle-income countries. Despite this, overall rates of non-ST-elevation myocardial infarction (NSTEMI) continue to rise. Furthermore, NSTEMI is a greater contributor to mortality after hospital discharge than ST-elevation myocardial infarction (STEMI). Patients with NSTEMI are often older, comorbid and have a high likelihood of multivessel coronary artery disease (MVD), which is associated with worse clinical outcomes. Currently, optimal treatment strategies for MVD in NSTEMI are less well established than for STEMI or stable coronary artery disease. Specifically, in relation to percutaneous coronary intervention (PCI) there is a paucity of randomized, prospective data comparing multivessel and culprit lesion-only PCI. Given the heterogeneous pathological basis for NSTEMI with MVD, an approach of complete revascularization may not be appropriate or necessary in all patients. Recognizing this, this review summarizes the limited evidence base for the interventional management of non-culprit disease in NSTEMI by comparing culprit-only and multivessel PCI strategies. We then explore how a personalized, precise approach to investigation, therapy and follow up may be achieved based on patient-, disease- and lesion-specific factors.
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http://dx.doi.org/10.1177/2040622320938527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331770PMC
July 2020

Statins for Primary Prevention in the Elderly: The Importance of Rigorous Evidence.

JAMA 2020 07;324(1):45-46

Duke Clinical Research Institute, Durham, North Carolina.

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http://dx.doi.org/10.1001/jama.2020.8390DOI Listing
July 2020

Statins in a Distorted Mirror of Media.

Curr Atheroscler Rep 2020 06 18;22(8):37. Epub 2020 Jun 18.

Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland Clinic, Cleveland Clinic JB-20, 9500 Euclid Ave, Cleveland, OH, 44195, USA.

Purpose Of Review: Statins have proven efficacy with a favorable safety profile yet, despite being widely affordable, remain profoundly underutilized. Statins have acquired a bad reputation, which is likely contributing to high rates of nonadherence and discontinuation. The degree to which negative media perceptions contribute to underutilization is unclear.

Recent Findings: The media has a key role in informing discussion on the public agenda but also on how issues are framed. In this context, the majority of studies evaluating news coverage suggest that the content on statins is predominantly negative and focused on potential harm. Studies utilizing quasi-experimental and interrupted time series design have shown periods of negative news stories on statins in multiple countries are associated with (a) less statin commencement in eligible patients, (b) high rates of discontinuation, and (c) poor long-term adherence. This review highlights the deleterious impact of negative media coverage on statin utilization through misattribution of muscle complaints and the nocebo effect. Academia must work with the media to harmonize the public health messaging; however, individual physicians have a critical role in mitigating a harmful narrative of misinformation and actively discredit malinformation.
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http://dx.doi.org/10.1007/s11883-020-00853-9DOI Listing
June 2020

Advancing Value-Based Models for Heart Failure: A Call to Action From the Value in Healthcare Initiative's Value-Based Models Learning Collaborative.

Circ Cardiovasc Qual Outcomes 2020 05 12;13(5):e006483. Epub 2020 May 12.

American Heart Association, Dallas, TX (N.B.).

Heart failure (HF) is a leading cause of hospitalizations and readmissions in the United States. Particularly among the elderly, its prevalence and costs continue to rise, making it a significant population health issue. Despite tremendous progress in improving HF care and examples of innovation in care redesign, the quality of HF care varies greatly across the country. One major challenge underpinning these issues is the current payment system, which is largely based on fee-for-service reimbursement, leads to uncoordinated, fragmented, and low-quality HF care. While the payment landscape is changing, with an increasing proportion of all healthcare dollars flowing through value-based payment models, no longitudinal models currently focus on chronic HF care. Episode-based payment models for HF hospitalization have yielded limited success and have little ability to prevent early chronic disease from progressing to later stages. The available literature suggests that primary care-based longitudinal payment models have indirectly improved HF care quality and cardiovascular care costs, but these models are not focused on addressing patients' longitudinal chronic disease needs. This article describes the efforts and vision of the multi-stakeholder Value-Based Models Learning Collaborative of The Value in Healthcare Initiative, a collaboration of the American Heart Association and the Robert J. Margolis, MD, Center for Health Policy at Duke University. The Learning Collaborative developed a framework for a HF value-based payment model with a longitudinal focus on disease management (to reduce adverse clinical outcomes and disease progression among patients with stage C HF) and prevention (an optional track to prevent high-risk stage B pre-HF from progressing to stage C). The model is designed to be compatible with prevalent payment models and reforms being implemented today. Barriers to success and strategies for implementation to aid payers, regulators, clinicians, and others in developing a pilot are discussed.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006483DOI Listing
May 2020

Targeting Vascular Calcification in Chronic Kidney Disease.

JACC Basic Transl Sci 2020 Apr 27;5(4):398-412. Epub 2020 Apr 27.

Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.

Cardiovascular (CV) disease remains an important cause of morbidity and mortality for patients with chronic kidney disease (CKD). Although clustering of traditional risk factors with CKD is well recognized, kidney-specific mechanisms are believed to drive the disproportionate burden of CV disease. One perturbation that is frequently observed at high rates in patients with CKD is vascular calcification, which may be a central mediator for an array of CV sequelae. This review summarizes the pathophysiological bases of intimal and medial vascular calcification in CKD, current strategies for diagnosis and management, and posits vascular calcification as a risk marker and therapeutic target.
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http://dx.doi.org/10.1016/j.jacbts.2020.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188874PMC
April 2020

Translating evidence from clinical trials of omega-3 fatty acids to clinical practice.

Future Cardiol 2020 07 17;16(4):343-350. Epub 2020 Mar 17.

Monash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, Australia.

The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) study recently demonstrated that administration of high doses of omega-3 fatty acids confers cardiovascular benefit in high-risk patients with the modest hypertriglyceridemia. This provided optimism for a therapeutic area that has challenged the field of cardiovascular prevention for 2 decades. However, it raises a number of questions including understanding the mechanism underscoring this benefit, how best to use these therapies and whether similar results will be observed with alternative omega-3 fatty acid preparations. Contemporary clinical trials of omega-3 fatty acids and their attempt to prevent cardiovascular events will be reviewed.
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http://dx.doi.org/10.2217/fca-2019-0031DOI Listing
July 2020

Ischaemic stroke in heart failure: back to basics?

Heart 2020 04 27;106(8):555-556. Epub 2020 Jan 27.

Duke Clinical Research Institute, Duke University, Durham, North Carolina, United States

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http://dx.doi.org/10.1136/heartjnl-2019-315957DOI Listing
April 2020

Reply to "Letter to the Editor: Aortic distensibility and coronary blood flow: does cardiac period play a role?"

Am J Physiol Heart Circ Physiol 2019 12;317(6):H1389

Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia.

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http://dx.doi.org/10.1152/ajpheart.00636.2019DOI Listing
December 2019

Anticoagulation-Related Major Bleeding in Patients With Atrial Fibrillation: Looking Behind the Curtain.

Circulation 2019 11 25;140(22):1802-1804. Epub 2019 Nov 25.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043318DOI Listing
November 2019

Current approach to the diagnosis of atherosclerotic coronary artery disease: more questions than answers.

Ther Adv Chronic Dis 2019 1;10:2040622319884819. Epub 2019 Nov 1.

South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5005, Australia.

Despite its commonality in routine clinical practice, the approach to a diagnosis of atherosclerotic coronary artery disease remains complex and, in part, contentious. The traditional dogma linking ischaemia to hard clinical outcomes has been questioned and reframed over the years; rather than being a predictor of hard clinical outcomes, the degree of ischaemia may simply be a marker of atherosclerotic disease burden. A renewed interest in the imaging of plaque burden has spawned the contemporary role of CT imaging for not only diagnosis and prognosis, but also for dictating downstream management. As the technology develops and evidence expands, decisions on investigative modalities remain centred around patient factors, local availability, test performance and cost. This review summarizes the available methods for diagnosis in the symptomatic patient and provides an overview of the current evidence behind functional and anatomical approaches.
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http://dx.doi.org/10.1177/2040622319884819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826912PMC
November 2019

High-Dose Omega-3 Fatty Acids in Cardiovascular Prevention: Finally Living Up to Their Potential?

Am J Cardiovasc Drugs 2020 Feb;20(1):11-18

Monash Cardiovascular Research Centre, Monash University, 246 Clayton Road, Clayton, VIC, 3168, Australia.

Despite the widespread use of statins in the setting of high cardiovascular risk, many patients continue to experience clinical events. This highlights the need to identify additional therapeutic strategies for high-risk patients. Interest in the use of omega-3 polyunsaturated fatty acids to prevent cardiovascular disease has been high for several decades. Despite promising results from before the statin era, many clinical trials have produced disappointing findings regarding products containing conventional doses of omega-3 fatty acids. More recent clinical trials using high doses of omega-3 fatty acids in targeted populations have suggested potential benefit when targeting the risk driven by atherogenic dyslipidemia. We review the clinical implications of completed and ongoing trials.
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http://dx.doi.org/10.1007/s40256-019-00363-3DOI Listing
February 2020

A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes: The Rapid Assessment of Possible Acute Coronary Syndrome in the Emergency Department With High-Sensitivity Troponin T Study (RAPID-TnT).

Circulation 2019 11 3;140(19):1543-1556. Epub 2019 Sep 3.

South Australian Department of Health, Adelaide (D.P.C., K.L., A.B., A.S., M.J.R.E., A.C., D.W., M.H., C.P.).

Background: High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED).

Methods: Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [<5 ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression.

Results: In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49-70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%, <0.001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4-6.4] hours versus standard arm: 5.6 (interquartile range, 4.0-7.1) hours, <0.001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%, <0.001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 17/1646 [1.0%] versus 16/1642 [1.0%]; incidence rate ratio, 1.06 [ 0.53-2.11], noninferiority value=0.006, superiority value=0.867), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0-99.9%) for 30-day death or myocardial infarction.

Conclusions: This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients.

Clinical Trial Registration: URL: https://www.anzctr.org.au. Unique identifier: ACTRN12615001379505.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042891DOI Listing
November 2019

Aortic distensibility is associated with both resting and hyperemic coronary blood flow.

Am J Physiol Heart Circ Physiol 2019 10 23;317(4):H811-H819. Epub 2019 Aug 23.

Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia.

A large body of evidence demonstrates an independent association between arterial stiffness and prospective risk of cardiovascular events. A reduction in coronary perfusion is presumed to underscore this association; however, studies confirming this are lacking. This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR)-derived aortic distensibility (AD). Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV) and CBF [π × (diameter) × APV × 0.125]. Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal descending aorta (DDA). Fifteen participants (53 ± 13 yr) with minor epicardial disease (maximum stenosis <30%) were enrolled. Resting CBF was 44.1 ± 11.9 mL/min, hyperemic CBF was 143.8 ± 37.4 mL/min, and CFVR was 3.15 ± 0.48. AD was 3.89 ± 1.72·10mmHg at the AA, 4.08 ± 1.80·10mmHg at the PDA, and 4.42 ± 1.67·10mmHg at the DDA. All levels of distensibility correlated with resting CBF ( = 0.350-0.373, < 0.05), hyperemic CBF ( = 0.453-0.464, < 0.01), and CFVR ( = 0.442-0.511, < 0.01). This study demonstrates that hyperemic and, to a lesser extent resting CBF, are significantly associated with measures of aortic stiffness in patients with only minor angiographic disease. These findings provide further in vivo support for the observed prognostic capacity of large artery function in cardiovascular event prediction. Cardiac magnetic resonance-derived aortic distensibility is associated with invasive measures of coronary blood flow. Large artery function is more strongly correlated with hyperemic than resting blood flow. Increased stiffness may represent a potential target for novel antianginal medications.
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http://dx.doi.org/10.1152/ajpheart.00067.2019DOI Listing
October 2019
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