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Appropriate use criteria (AUC) have been developed to promote the rational use of percutaneous coronary intervention (PCI) among clinicians and to provide benchmarking feedback to hospitals. The original AUC were published in 2012 and subsequently updated in 2017 to reflect emerging, contemporary evidence however the degree to which the updated guidance re-classifies PCI appropriateness is unknown.Elective PCI cases from March 1, 2018 until June 30, 2021 were identified from within the NCDR CathPCI database. PCI cases were classified as 'appropriate,' 'uncertain' or 'inappropriate' under 2012 AUC and 'appropriate,' 'may be appropriate' or 'rarely appropriate' under 2017 AUC; those with missing data elements were termed 'not mappable.' Groups that 'remained appropriate' (appropriate in both 2012 and 2017), 'became non-appropriate' ('appropriate' in 2012 but became either 'may be appropriate' or 'rarely appropriate in 2017) and 'became appropriate' ('appropriate' in 2017 but were 'uncertain' or 'inappropriate' in 2012) were descriptively compared. Concordance was assessed by calculation of Cohen's Kappa.A total of 245,196 patients underwent elective PCI across 1669 centers. By 2012 AUC, 44% were classified 'appropriate,' 28% were 'uncertain' and 16% were 'inappropriate' compared with 2017 AUC which considered 34% 'appropriate', 56% may be 'appropriate' and 4% 'rarely appropriate'. Overall fair agreement was observed with a Kappa statistic of 0.40 (95%CI 0.396-0.403). Compared with PCI that 'remained appropriate' under the 2017 AUC, PCI that 'became non-appropriate' in 2017 were more likely to be asymptomatic, less likely to be on anti-anginals and less likely to have complex lesions. Compared with PCI that 'became non-appropriate', PCI that 'became appropriate' had a higher proportion of atypical and non-anginal symptoms and were less likely to have had positive functional tests. Procedural related outcomes were similar across all groups. A total of 29 429 PCI (12.0%) were not mappable by 2012 AUC while 16 077 (6.6%) were not mappable by 2017 AUC.In this contemporary analysis of patients undergoing PCI in the United States, only fair agreement between the 2012 and updated 2017 AUC was observed. While some of this reflects the intention of the updated guidance, the large proportion that were considered 'maybe appropriate' or who 'became non-appropriate' reflect the difficulties of documenting and implementing contemporary AUC guidance.

Purpose of reviewTo review recent developments in the field of cholesteryl ester transfer protein (CETP) inhibition from clinical trials and genomic analyses which have the potential to impact future clinical programs.Recent findingsCETP plays an important role in remodelling of lipoproteins. A large body of evidence suggests that the presence of low CETP activity should have favourable effects on lipid profiles and cardiovascular risk. However, a number of clinical development programs of pharmacological CETP inhibitors have been disappointing with reports of toxicity and clinical futility. These findings have led many to consider abandoning CETP inhibition as a potential strategy for cardiovascular prevention. However, recent observations from genomic analyses and post hoc observations of prior clinical trials have given greater insights into the potential relationship between CETP inhibition and cardiovascular risk. This has highlighted the importance of lowering levels of atherogenic lipoproteins.SummaryThese findings provide a pathway for ongoing clinical development of CETP inhibitors, where the potential to play an important role in the prevention of cardiovascular disease may still be possible. The lessons learned and pathway forward for new CETP inhibitors will be reviewed.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) improve the risk for heart and kidney failure. However, their effects on major atherosclerotic cardiovascular events (MACE) are less clear. Although outcomes trials of drugs for diabetes were not powered to prove superiority, the totality of trial data yields an estimate of ∼11% relative reduction for MACE (HR 0.89, 95%CI 0.82-0.96) and neutral on stroke (HR 0.92, 95%CI 0.79-1.08). In animal models, SGLT-2i favorably affects plaque size, composition, and inflammatory pathways; human data in this regard are lacking. Ongoing trials are evaluating SGLT-2i efficacy in heart failure, kidney disease, and postmyocardial infarction populations, independent of diabetes status.

Purpose Fractional flow reserve (FFR) has been demonstrated in some studies to predict long-term coronary artery bypass graft (CABG) patency. Quantitative flow ratio (QFR) is an emerging technology which may predict FFR. In this study, we hypothesised that QFR would predict long-term CABG patency and that QFR would offer superior diagnostic performance to quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). Methods A prospective study was performed on patients with left main coronary artery disease who were undergoing CABG. QFR, QCA and IVUS assessment was performed. Follow-up computed tomography coronary angiography and invasive coronary angiography was undertaken to assess graft patency. Results A total of 22 patients, comprising of 65 vessels were included in the analysis. At a median follow-up of 3.6 years post CABG (interquartile range, 2.3 to 4.8 years), 12 grafts (18.4%) were occluded. QFR was not statistically significantly higher in occluded grafts (0.81 ± 0.19 vs. 0.69 ± 0.21; P = 0.08). QFR demonstrated a discriminatory power to predict graft occlusion (area under the receiver operating characteristic curve, 0.70; 95% confidence interval [CI], 0.52 to 0.88; P = 0.03). At long-term follow-up, the risk of graft occlusion was higher in vessels with a QFR > 0.80 (58.6% vs. 17.0%; hazard ratio, 3.89; 95% CI, 1.05 to 14.42; P = 0.03 by log-rank test). QCA (minimum lumen diameter, lesion length, diameter stenosis) and IVUS (minimum lumen area, minimum lumen diameter, diameter stenosis) parameters were not predictive of long-term graft patency. Conclusions QFR may predict long-term graft patency in patients undergoing CABG.

Immune checkpoint inhibitors (ICI) are cancer therapies that have been associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood pressure (BP) measurements are routinely performed during day oncology center visits for administration of ICI therapy but are often not assessed temporally to screen and monitor hypertension, which could independently increase the risk of ASCVD in cancer survivorship. This study reports the feasibility of using serial BP measurements from routine visits to day oncology center to diagnose and monitor hypertension control in cancer patients receiving ICIs.

Dyslipidemia therapeutics have primarily focused on lowering levels of low-density lipoprotein cholesterol. However, many patients continue to experience cardiovascular events, despite effective lowering of LDL-C. This has prompted efforts to target additional risk factors to achieve more effective prevention of cardiovascular disease. Emerging evidence suggests that triglyceride rich lipoproteins play a causal role in atherosclerosis, highlighting the potential for specific therapeutic lowering.(1) Evidence to support the causal role of triglyceride rich lipoproteins in atherosclerotic cardiovascular disease. (2) Use of existing lipid modifying therapies to target triglyceride rich lipoproteins. (3) Development of novel therapeutic agents that target triglyceride rich lipoproteins and their potential impact on cardiovascular risk.Evidence from preclinical, observational and genetic studies highlight the role of triglyceride rich lipoproteins in the causal pathway of atherosclerotic cardiovascular disease. A number of existing agents have the potential to reduce residual cardiovascular risk associated with hypertriglyceridemia. However, emerging agents have the potential to substantially and preferentially lower triglyceride levels beyond contemporary therapeutics. How they will modulate cardiovascular risk will ultimately be determined by large clinical outcomes trials. They do provide the opportunity to substantially influence the way we target dyslipidemia in the prevention of cardiovascular disease.

The contemporary uptake of lipid-lowering therapies (LLT), including more intensive treatment with high-intensity statins and non-statin LLT, among U.S. older adults (≥75 years old) with ASCVD is unknown.In this multicenter retrospective cohort study of a large geographically diverse sample of commercially insured U.S. older adults with ASCVD, we assessed treatment with LLT. Secondary measures included LDL-C above target ≥70 mg/dl, persistence and adherence to therapy.Treatment with statins, high-intensity statins, ezetimibe, and PCSK9 inhibitors was assessed in 194,503 older adults (49.9% female) with known ASCVD on January 31st, 2019. 49.3% of older adults with ASCVD were on any statin, with 16.6% receiving a high-intensity statin and 32.7% on low-or moderate-intensity statins. Treatment with ezetimibe (2.4%) or PCSK9 inhibitors (0.24%) was rare and 62.6% of the overall cohort had an LDL-C above target at ≥70 mg/dl. Patients on high-intensity statins were more frequently male, had a diagnosis of coronary artery disease, and were more frequently seen by a cardiologist compared with those on low-or moderate-intensity statins and untreated individuals (p 0.0001). The majority of older adults on high-intensity statins remained on therapy at 12 months (91.9%) and 85.7% had ≥75% adherence to treatment.Less than half of eligible older adults with ASCVD are on statins and only a minority of patients are receiving more intensive lipid-lowering to improve outcomes.

Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.

ImportanceProfessional societies and the Centers for Medicare & Medicaid Services suggest volume thresholds to ensure quality in transcatheter aortic valve implantation (TAVI).ObjectiveTo model the association of volume thresholds vs spoke-and-hub implementation of outcome thresholds with TAVI outcomes and geographic access.Design, Setting, and ParticipantsThis cohort study included patients who enrolled in the US Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry. Site volume and outcomes were determined from a baseline cohort of adults undergoing TAVI between July 1, 2017, and June 30, 2020.ExposuresWithin each hospital referral region, TAVI sites were categorized by volume (Main Outcomes and MeasuresThe primary outcome was the absolute difference in events between the adjusted observed and modeled 30-day composite of death, stroke, major bleeding, stage III acute kidney injury, and paravalvular leak. Data are presented as the number of events reduced under the above scenarios with 95% bayesian credible intervals (CrIs) and median (IQR) driving distance.ResultsThe overall cohort included 166 248 patients with a mean (SD) age of 79.5 (8.6) years; 74 699 (47.3%) were female and 6657 (4.2%) were Black; 158 025 (95%) were treated in higher-volume sites (≥50 TAVIs) and 75 088 (45%) were treated in best-outcome sites. Modeling a volume threshold, there was no significant reduction in estimated adverse events (−34; 95% CrI, −75 to 8), while the median (IQR) driving time from the existing site to the alternate site was 22 (15-66) minutes. Transitioning care to the best outcome site in a hospital referral region resulted in an estimated 1261 fewer adverse outcomes (95% CrI, 1013-1500), while the median (IQR) driving time from the original site to the best site was 23 (15-41) minutes. Directionally similar findings were observed for Black individuals, Hispanic individuals, and individuals from rural areas.Conclusions and RelevanceIn this study, compared with the current system of care, a modeled outcome-based spoke-and-hub paradigm of TAVI care improved national outcomes to a greater extent than a simulated volume threshold, at the cost of increased driving time. To improve quality while maintaining geographic access, efforts should focus on reducing site variation in outcomes.

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 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%]; P =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%]; P =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]; P =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]; P =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.

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 ( 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.

Several medications that are proven to reduce cardiovascular events exist for individuals with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease, however they are substantially underused in clinical practice. Clinician, patient, and system-level barriers all contribute to these gaps in care; yet, there is a paucity of high quality, rigorous studies evaluating the role of interventions to increase utilization. The COORDINATE-Diabetes trial randomized 42 cardiology clinics across the United States to either a multifaceted, site-specific intervention focused on evidence-based care for patients with T2DM or standard of care. The multifaceted intervention comprised the development of an interdisciplinary care pathway for each clinic, audit-and-feedback tools and educational outreach, in addition to patient-facing tools. The primary outcome is the proportion of individuals with T2DM prescribed three key classes of evidence-based medications (high-intensity statin, angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and either a sodium/glucose cotransporter-2 inhibitor (SGLT-2i) inhibitor or glucagon-like peptide 1 receptor agonist (GLP-1RA) and will be assessed at least 6 months after participant enrollment. COORDINATE-Diabetes aims to identify strategies that improve the implementation and adoption of evidence-based therapies.

ObjectivePrior data have shown rising acute myocardial infarction (MI) trends in Australia; whether these increases have continued in recent years is not known. This study thus sought to characterise contemporary nationwide trends in MI hospitalisations and coronary procedures in Australia and their associated economic burden.MethodsThe primary outcome measure was the incidence and time trends of total MI, ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) hospitalisations from 1993 to 2017. The incidence and time trends of coronary procedures were additionally collected, alongside MI hospitalisation costs.ResultsAdjusted for population changes, annual MI incidence increased from 216.2 cases per 100 000 to a peak of 270.4 in 2007 with subsequent decline to 218.7 in 2017. Similarly, NSTEMI incidence increased from 68.0 cases per 100 000 in 1993 to a peak of 192.6 in 2007 with subsequent decline to 162.6 in 2017. STEMI incidence decreased from 148.3 cases per 100 000 in 1993 to 56.2 in 2017. Across the study period, there were annual increases in MI hospitalisations of 0.7% and NSTEMI hospitalisations of 5.6%, and an annual decrease in STEMI hospitalisations of 4.8%. Angiography and percutaneous coronary intervention increased by 3.4% and 3.3% annually, respectively, while coronary artery bypass graft surgery declined by 2.2% annually. MI hospitalisation costs increased by 100% over the study period, despite a decreased average length of stay by 45%.ConclusionsThe rising incidence of MI hospitalisations appear to have stabilised in Australia. Despite this, associated healthcare expenditure remains significant, suggesting a need for continual implementation of public health policies and preventative strategies.

Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have improved the use of high-intensity statins is unknown.This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD.In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities.Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence.Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD.

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.

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 2667 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.

Background The practice pattern and outcome of medical devices following their regulatory approval may differ by country. The aim of this study is to compare postapproval national clinical registry data on transcatheter aortic valve replacement between the United States and Japan on patient characteristics, periprocedural outcomes, and the variability of outcomes as a part of a partnership program (Harmonization‐by‐Doing) between the 2 countries. Methods and Results The patient‐level data were extracted from the US Society of Thoracic Surgeons /American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) and the J‐TVT (Japanese Transcatheter Valvular Therapy) registry, respectively, to analyze transcatheter aortic valve replacement outcomes between 2013 and 2019. Data entry for these registries was mandated by the federal regulators, and the majority of variable definitions were harmonized to allow direct data comparison. A total of 244 722 transcatheter aortic valve replacements from 646 institutions in the United States and 26 673 transcatheter aortic valve replacements from 171 institutions in Japan were analyzed. Median volume per site was 65 (interquartile range, 45–97) in the United States and 28 (interquartile range, 19–41) in Japan. Overall, patients in J‐TVT were older (United States: mean‐age, 80.1±8.7 versus Japan: 84.4±5.2; P P P P P P Conclusions This collaborative analysis between the United States and Japan demonstrated the feasibility of international comparison using the national registries coded under mutual variable definitions. Both countries obtained excellent outcomes, although the Japanese had lower 30‐day mortality and major morbidity. Harmonization‐by‐Doing is one of the key steps needed to build global‐level learning to improve patient outcomes.

Based on contemporary estimates in the US, evidence-based therapies for cardiovascular risk reduction are generally underused among patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).To determine the use of evidence-based cardiovascular preventive therapies in a broad US population with diabetes and ASCVD.This multicenter cohort study used health system-level aggregated data within the National Patient-Centered Clinical Research Network, including 12 health systems. Participants included patients with diabetes and established ASCVD (ie, coronary artery disease, cerebrovascular disease, and peripheral artery disease) between January 1 and December 31, 2018. Data were analyzed from September 2020 until January 2021.One or more health care encounters in 2018.Patient characteristics by prescription of any of the following key evidence-based therapies: high-intensity statin, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) and sodium glucose cotransporter-2 inhibitors (SGLT2I) or glucagon-like peptide-1 receptor agonist (GLP-1RA).The overall cohort included 324 706 patients, with a mean (SD) age of 68.1 (12.2) years and 144 169 (44.4%) women and 180 537 (55.6%) men. A total of 59 124 patients (18.2% ) were Black, and 41 470 patients (12.8%) were Latinx. Among 205 885 patients with specialized visit data from the prior year, 17 971 patients (8.7%) visited an endocrinologist, 54 330 patients (26.4%) visited a cardiologist, and 154 078 patients (74.8%) visited a primary care physician. Overall, 190 277 patients (58.6%) were prescribed a statin, but only 88 426 patients (26.8%) were prescribed a high-intensity statin; 147 762 patients (45.5%) were prescribed an ACEI or ARB, 12 724 patients (3.9%) were prescribed a GLP-1RA, and 8989 patients (2.8%) were prescribed an SGLT2I. Overall, 14 918 patients (4.6%) were prescribed all 3 classes of therapies, and 138 173 patients (42.6%) were prescribed none. Patients who were prescribed a high-intensity statin were more likely to be men (59.9% [95% CI, 59.6%-60.3%] of patients vs 55.6% [95% CI, 55.4%-55.8%] of patients), have coronary atherosclerotic disease (79.9% [95% CI, 79.7%-80.2%] of patients vs 73.0% [95% CI, 72.8%-73.3%] of patients) and more likely to have seen a cardiologist (40.0% [95% CI, 39.6%-40.4%] of patients vs 26.4% [95% CI, 26.2%-26.6%] of patients).In this large cohort of US patients with diabetes and ASCVD, fewer than 1 in 20 patients were prescribed all 3 evidence-based therapies, defined as a high-intensity statin, either an ACEI or ARB, and either an SGLT2I and/or a GLP-1RA. These findings suggest that multifaceted interventions are needed to overcome barriers to the implementation of evidence-based therapies and facilitate their optimal use.

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 TG150 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, p0.001), had higher BMI (32 vs 30 kg/m

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.

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.

Central Illustration, Highlights • Vascular calcification is a highly regulated, cell-mediated process that is strongly associated with CKD and confers increased risk for incident CV events. • Multiple pathways link vascular calcification with CKD; however, they remain incompletely understood, and the development of targeted therapies has been underwhelming. • Illumination of the causal steps and natural history that link vascular calcification to CV events will affirm its role as a CV risk factor and accelerate drug discovery and therapeutic translation., Summary 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.

Technical advancements together with robust clinical trial evidence continue to extend the reach of transcatheter therapies. Conditions once considered amenable only to surgery, are now treatable percutaneously offering not only safe outcomes, but in some cases, superior results. Whilst ongoing clinical trials will inform which patients are likely to benefit from either approach, safe transcatheter alternatives have been transformative for patients considered unfit for surgery. We present a case from our institution of a septuagenarian with both aortic stenosis and hypertrophic cardiomyopathy deemed unfit for surgery by a porcelain aorta. Alcohol septal ablation (ASA) and transcatheter aortic valve replacement (TAVR) were offered, however in the context of treatment for active malignancy, a previously planned staged intervention had to be performed in a single procedure due to the development of heart failure symptoms. We present the first description of this ‘two-in-one’ intervention and provide background literature review for both ASA and TAVR.

ImportanceThere is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure.MethodsA nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1–22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG).ResultsST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52–0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up.ConclusionsThere are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes.Trial Registration4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Background: Percutaneous coronary intervention is performed by operators with differing experience, technique, and case mix. It is unknown if operator practice patterns impact patient outcomes. We sought to determine if a cluster algorithm can identify distinct profiles of percutaneous coronary intervention operators and if these profiles are associated with patient outcomes. Methods: Operators performing at least 25 annual procedures between 2014 and 2018 were clustered using an agglomerative hierarchical clustering algorithm. Risk-adjusted in-hospital mortality was compared between clusters. Results: We identified 4 practice profiles among 7706 operators performing 2 937 419 procedures. Cluster 1 (n=3345) demonstrated case mix and practice patterns similar to the national median. Cluster 2 (n=1993) treated patients with lower clinical acuity and were less likely to use intracoronary diagnostics, atherectomy, and radial access. Cluster 3 (n=1513) had the lowest case volume, were more likely to work at rural hospitals, and cared for a higher proportion of patients with ST-segment–elevation myocardial infarction and cardiogenic shock. Cluster 4 (n=855) had the highest case volume, were most likely to treat patients with high anatomic complexity and use atherectomy, intracoronary diagnostics, and mechanical support. Compared with cluster 1, adjusted in-hospital mortality was similar for cluster 2 (estimated difference, −0.03 [95% CI, −0.10 to 0.04]), higher for cluster 3 (0.14 [0.07–0.22]), and lower for cluster 4 (−0.15 [−0.24 to −0.06]). Conclusions: Distinct percutaneous coronary intervention operator profiles are differentially associated with patient outcomes. A phenotypic approach to physician assessment may provide actionable feedback for quality improvement.

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 [ 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%, P P P P value=0.001, superiority P value=0.744), 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.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. Studies investigating the disproportionate burden of cardiovascular disease have occurred predominantly in the peripheral vasculature, often used noninvasive imaging modalities, and infrequently recruited patients receiving dialysis. This study sought to evaluate invasive coronary dynamic vascular function in patients with end-stage renal failure (ESRF).Patients referred for invasive coronary angiography prior to renal transplantation were invited to participate. Control patients were recruited in parallel. Baseline characteristics were obtained. Coronary diameter (via quantitative coronary angiography) and coronary blood flow (via Doppler Flowire) were measured; macrovascular endothelial-dependent and independent effects were evaluated in response to intracoronary acetylcholine infusion (10 and 10 mol/l) and intracoronary glyceryl trinitrate, respectively. Microvascular function was evaluated by response to adenosine and expressed as coronary flow velocity reserve. Mean values were compared.Thirty patients were evaluated: 15 patients with ESRF (mean age 52.1 ± 9, male 73%) and 15 control patients (mean age 53.3 ± 13, male 60%). Comorbidity profile, aside from ESRF, was well matched. Baseline coronary blood flow was similar between groups (101.6 ± 10.3 vs. 103.4 ± 9.1 ml/min, P = 0.71), as was endothelial-dependent response to acetylcholine (159.1 ± 16.9 vs. 171.1 ± 16.8 ml/min, P = 0.41). Endothelial-independent response to glyceryl trinitrate was no different between groups (14.3 ± 3.1 vs. 13.1 ± 2.3%, P = 0.73. A significantly reduced coronary flow velocity reserve was observed in the ESRF cohort compared to controls (2.34 ± 0.4 vs. 3.05 ± 0.3, P = 0.003).Patients with ESRF had preserved endothelial-dependent function however compared to controls, demonstrated significantly attenuated microvascular reserve. An impaired response to adenosine may not only represent a component of the pathophysiological milieu in patients with ESRF but may also provide a basis for the suboptimal diagnostic performance of vasodilatory stress in this population.

The American Society for Preventive Cardiology (ASPC) "Ten things to know about ten cardiovascular disease risk factors - 2022" is a summary document regarding cardiovascular disease (CVD) risk factors. This 2022 update provides summary tables of ten things to know about 10 CVD risk factors and builds upon the foundation of prior annual versions of "Ten things to know about ten cardiovascular disease risk factors" published since 2020. This 2022 version provides the perspective of ASPC members and includes updated sentinel references (i.e., applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful dietary intake, physical inactivity, dyslipidemia, pre-diabetes/diabetes, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis (with smoking as a potential contributor to thrombosis), kidney dysfunction and genetics/familial hypercholesterolemia. Other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the ASPC "Ten things to know about ten cardiovascular disease risk factors - 2022" to provide a tabular overview of things to know about ten of the most common CVD risk factors applicable to preventive cardiology and provide ready access to applicable guidelines and sentinel reviews.

INTRODUCTION Elevated levels of low-density lipoprotein (LDL) cholesterol have been unequivocally demonstrated to play a causal role in atherosclerotic cardiovascular disease. The last thirty years has witnessed a generation of clinical trials that have demonstrated a reduction in cardiovascular risk with use of increasing intensive lipid lowering regimens involving statin therapy in combination with other agents. However, many patients fail to achieve treatment mandated LDL cholesterol goals. This highlights the need to develop additional approaches to lower LDL cholesterol levels. AREAS COVERED (i) Contemporary data highlighting the atherogenicity of LDL cholesterol and cardiovascular benefits of current lipid lowering therapies. (ii) Importance of statin intolerance and inability to achieve LDL cholesterol goals in driving ongoing cardiovascular risk. (iii) Emergence of new therapeutic agents designed to achieve more effective lowering of LDL cholesterol. EXPERT OPINION Effective lowering of LDL cholesterol plays a critical role in approaches to the prevention of cardiovascular disease. A greater number of patients will require combinations of agents to achieve optimal lipid control. Accordingly, new agents will be required to provide sufficient choice for patients at high cardiovascular risk.