Lifelong Aspirin for All in the Secondary Prevention of Chronic Coronary Syndrome: Still Sacrosanct or Is Reappraisal Warranted?

Four decades have passed since the first trial suggesting the efficacy of aspirin in the secondary prevention of myocardial infarction. Further trials, collectively summarized by the Antithrombotic Trialists' Collaboration, solidified the historical role of aspirin in secondary prevention. Although the benefit of aspirin in the immediate phase after a myocardial infarction remains incontrovertible, a number of emerging lines of evidence, discussed in this narrative review, raise some uncertainty as to the primacy of aspirin for the lifelong management of all patients with chronic coronary syndrome (CCS). For example, data challenging the previously unquestioned role of aspirin in CCS have come from recent trials where aspirin was discontinued in specific clinical scenarios, including early discontinuation of the aspirin component of dual antiplatelet therapy after percutaneous coronary intervention and the withholding of aspirin among patients with both CCS and atrial fibrillation who require anticoagulation. Recent primary prevention trials have also failed to consistently demonstrate net benefit for aspirin in patients treated to optimal contemporary cardiovascular risk factor targets, indicating that the efficacy of aspirin for secondary prevention of CCS may similarly have changed with the addition of more modern secondary prevention therapies. The totality of recent evidence supports further study of the universal need for lifelong aspirin in secondary prevention for all adults with CCS, particularly in stable older patients who are at highest risk for aspirin-induced bleeding.

The rise and fall of aspirin in the primary prevention of cardiovascular disease.

Aspirin is one of the most frequently used drugs worldwide and is generally considered effective for the secondary prevention of cardiovascular disease. By contrast, the role of aspirin in primary prevention of cardiovascular disease is controversial. Early trials evaluating aspirin for primary prevention, done before the turn of the millennium, suggested reductions in myocardial infarction and stroke (although not mortality), and an increased risk of bleeding. In an effort to balance the risks and benefits of aspirin, international guidelines on primary prevention of cardiovascular disease have typically recommended aspirin only when a substantial 10-year risk of cardiovascular events exists. However, in 2018, three large randomised clinical trials of aspirin for the primary prevention of cardiovascular disease showed little or no benefit and have even suggested net harm. In this narrative Review, we reappraise the role of aspirin in primary prevention of cardiovascular disease, contextualising data from historical and contemporary trials.

Fluoropyrimidine-Associated Cardiotoxicity: A Retrospective Case-Control Study.

BACKGROUND: The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS: In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS: We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p < .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION: Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity.

Gender differences in industry payments among cardiologists.

BACKGROUND: There is a wage gap among men and women practicing cardiology. Differences in industry funding can be both a consequence of and a contributor to gender differences in salaries. We sought to determine whether gender differences exist in the distribution, types, and amounts of industry payments among men and women in cardiology. METHODS: In this cross-sectional analysis, we used the Centers for Medicare & Medicaid Services Open Payment program database to obtain 2016 industry payment data for US cardiologists. We also used UK Disclosure data to obtain 2016 industry payments to UK cardiologists. Outcomes included the proportions of male and female cardiologists receiving industry funding and the mean industry payment amounts received by male and female cardiologists. Where possible, we also assessed 2014 and 2015 data in both locations. RESULTS: Of the 22,848 practicing Centers for Medicare & Medicaid Services US cardiologists in 2016, 20,037 (88%) were men and 2,811 (12%) were women. Proportionally more men than women received industry payments in 2016 (78.0% vs 68.5%, respectively; P < .001). Men received higher overall mean industry payments than women ($6,193.25 vs. $2,501.55, P < .001). Results were similar in 2014 and 2015. Among UK cardiologists, more men (24.4%) than women (13.5%) received industry payments in 2016 (P < .001). However, although the difference in overall industry payments was numerically larger among men compared to women, this did not achieve statistical significance (£2,348.31 vs £1,501.37, respectively, P = .35). CONCLUSIONS: Industry payments to cardiologists are common, and there are gender differences in these payments on both sides of the Atlantic.

Qualitative Assessment of Clerkship Students' Perspectives of the Topics of Pain and Addiction in their Preclinical Curriculum.

OBJECTIVE: A majority of physicians feel poorly trained in the treatment of chronic pain and addiction. As such, it is critical that medical students receive appropriate education in both pain management and addiction. The purpose of this study was to assess the pre-clinical curriculum in pain medicine and addiction from the perspective of students after they had completed their pre-clinical training and to assess what they perceived as the strengths and weaknesses of their training. METHODS: The authors conducted focused interviews among clinical medical students who had completed at least 6 months of clerkships. The interviews targeted the students' retrospective opinions about the pre-clinical curriculum and their preparedness for clinical encounters with either pain or addiction-related issues during their rotations. Coders thematically analyzed the de-identified interview transcripts, with consensus reached through discussion and code modification. RESULTS: Themes that emerged through the focused interviews included: fragmented curricular structure (and insufficient time) for pain and addiction medicine, not enough specific treatment strategies for pain or addiction, especially for complex clinical scenarios, and lack of a trained work-force to provide guidance in the management of pain and addiction. CONCLUSION: This study demonstrated the feasibility of gathering student perspectives to inform changes to improve the pre-clinical curriculum in pain and addiction medicine. Students identified multiple areas for improvement at the pre-clerkship level, which have informed updates to the curriculum. More research is needed to determine if curricular changes based on student feedback lead to improved learning outcomes.

Estimation of individual cumulative ultraviolet exposure using a geographically-adjusted, openly-accessible tool.

BACKGROUND: Estimates of an individual's cumulative ultraviolet (UV) radiation exposure can be useful since ultraviolet radiation exposure increases skin cancer risk, but a comprehensive tool that is practical for use in the clinic does not currently exist. The objective of this study is to develop a geographically-adjusted tool to systematically estimate an individual's self-reported cumulative UV radiation exposure, investigate the association of these estimates with skin cancer diagnosis, and assess test reliability. METHODS: A 12-item online questionnaire from validated survey items for UV exposure and skin cancer was administered to online volunteers across the United States and results cross-referenced with UV radiation indices. Cumulative UV exposure scores (CUES) were calculated and correlated with personal history of skin cancer in a case-control design. Reliability was assessed in a separate convenience sample. RESULTS: 1,118 responses were included in the overall sample; the mean age of respondents was 46 (standard deviation 15, range 18 - 81) and 150 (13 %) reported a history of skin cancer. In bivariate analysis of 1:2 age-matched cases (n = 149) and controls (n = 298), skin cancer cases were associated with (1) greater CUES prior to first skin cancer diagnosis than controls without skin cancer history (242,074 vs. 205,379, p = 0.003) and (2) less engagement in UV protective behaviors (p < 0.01). In a multivariate analysis of age-matched data, individuals with CUES in the lowest quartile were less likely to develop skin cancer compared to those in the highest quartile. In reliability testing among 19 volunteers, the 2-week intra-class correlation coefficient for CUES was 0.94. We have provided the programming code for this tool as well as the tool itself via open access. CONCLUSIONS: CUES is a useable and comprehensive tool to better estimate lifetime ultraviolet exposure, so that individuals with higher levels of exposure may be identified for counseling on photo-protective measures.

Trends in Blood Pressure Treatment Intensification in Older Adults With Hypertension in the United States, 2008 to 2018.

BACKGROUND: Hypertension control has worsened nationally, and treatment intensification is important for control. National trends for appropriate blood pressure intensification for older adults are unknown. We determine the proportion of ambulatory visits where older adults with hypertension were appropriately intensified on antihypertensives from 2008 to 2018. METHODS: Data from National Ambulatory Medical Care Survey were used. National Ambulatory Medical Care Survey is a nationally representative sample of ambulatory visits. Adults 60 years or older were included. Appropriate antihypertensive intensification was defined as addition of an antihypertensive for a blood pressure reading above target. We examined appropriate intensification by blood pressure targets set by the American College of Cardiology-American Heart Association, the European Society of Cardiology, and the American College of Physicians-American Academy of Family Physicians guidelines for older adults. Further, we defined an additional all-inclusive criterion meeting all 3 guidelines. RESULTS: From 2008 to 2018, appropriate intensification by American College of Cardiology/American Heart Association occurred at 11.1% (95% CI, 9.8%-12.5%) of visits, decreasing from 13.6% (95% CI, 15.6%-28.7%) of visits in 2008 to 2009 to 10.4% (95% CI, 10.9%-26.4%) in 2015 to 2018. Appropriate intensification by European Society of Cardiology occurred at 14.2% (12.1%-16.6%) of visits over 2008 to 2018, decreasing from 16.9% (95% CI, 13.5%-21.0%) in 2008 to 2009 to 12.5% (95% CI, 7.4%-20.3%) from 2015 to 2018. Appropriate intensification by American Academy of Family Physicians/American College of Physicians occurred at 18.9% (16.2%-22.0%) of visits over 2008 to 2018, decreasing from 24.7% (95% CI, 20.2%-29.0%) in 2008 to 2009 to 14.9% (95% CI, 9.0%-23.7%) from 2015 to 2018. By all-inclusive criteria, intensification trended toward worsening with time: odds ratio: 0.93 ([95% CI, 0.87-1.00]; P=0.07). CONCLUSIONS: Appropriate treatment intensification for older adults with hypertension in the United States was suboptimal over the past decade.

Implementation of High-Sensitivity Cardiac Troponin Assays in the United States.

BACKGROUND: Few data exist regarding the implementation of high-sensitivity cardiac troponin (hs-cTn) assays in the United States since their approval. OBJECTIVES: This study sought to explore trends in hs-cTn assay implementation over time and assess the association of their use with in-hospital cardiac testing and outcomes. METHODS: The study examined trends in implementation of hs-cTn assays among participating hospitals in the National Cardiovascular Data Registry Chest Pain-MI [Myocardial Infarction] Registry from January 1, 2019 through September 30, 2021. Associations among hs-cTn use, use of in-hospital diagnostic imaging, and patient outcomes were assessed using generalized estimating equation models with logistic or gamma distributions. RESULTS: Among 550 participating hospitals (N = 251,000), implementation of hs-cTn assays increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (Ptrend < 0.001). Use of hs-cTn was associated with more echocardiography among persons with non-ST-segment elevation acute coronary syndrome (NSTE-ACS; 82.4% vs 75.0%; adjusted odds ratio: 1.43; 95% CI: 1.19-1.73) but not among low-risk chest pain individuals. Use of hs-cTn was associated with less invasive coronary angiography among low-risk patients (3.7% vs 4.5%; adjusted odds ratio: 0.73; 95% CI: 0.58-0.92) but similar use for patients with NSTE-ACS. There was no association between hs-cTn use and noninvasive stress testing or coronary computed tomography angiography testing. Among individuals with NSTE-ACS, hs-cTn use was not associated with revascularization or in-hospital mortality. Use of hs-cTn was associated with a shorter length of stay (median 47.6 hours vs 48.0 hours; ratio: 0.94; 95% CI: 0.90-0.98). CONCLUSIONS: Implementation of hs-cTn among U.S. hospitals is increasing, but most U.S. hospitals continue to use less sensitive assays. The use of hs-cTn was associated with modestly shorter length of stay, greater use of echocardiography for NSTE-ACS, and less use of invasive angiography among low-risk patients.

Moderate aortic stenosis: culprit or bystander?

Non-rheumatic aortic stenosis (AS) is among the most common valvular diseases in the developed world. Current guidelines support aortic valve replacement (AVR) for severe symptomatic AS, which carries high morbidity and mortality when left untreated. In contrast, moderate AS has historically been thought to be a benign diagnosis for which the potential benefits of AVR are outweighed by the procedural risks. However, emerging data demonstrating the substantial mortality risk in untreated moderate AS and substantial improvements in periprocedural and perioperative mortality with AVR have challenged the traditional risk/benefit paradigm. As such, an appraisal of the contemporary data on morbidity and mortality associated with moderate AS and appropriate timing of valvular intervention in AS is warranted. In this review, we discuss the current understanding of moderate AS, including the epidemiology, current surveillance and management guidelines, clinical outcomes, and future studies.

Wide Complex Tachycardia and Cardiac Arrest During Endoscopy.

A 59-year-old man presented for implantable cardioverter-defibrillator placement after a wide QRS complex tachycardia cardiac arrest at an outside hospital. In this case report, we discuss the differential diagnosis of this patient's tachyarrhythmia and the electrophysiological studies that established the diagnosis and guided management. (Level of Difficulty: Intermediate.).

Cost-Effectiveness of Antibiotic-Eluting Envelope for Prevention of Cardiac Implantable Electronic Device Infections in Heart Failure.

BACKGROUND: Use of an antibiotic-eluting envelope (AEE) during cardiac implantable electronic device procedures reduces infection risk but increases procedural costs. We aim to estimate the cost-effectiveness of AEE use during cardiac implantable electronic device procedures among patients with heart failure. METHODS: A state-transition cohort model of heart failure patients undergoing cardiac implantable electronic device implantation or generator replacement was developed with input parameters estimated from randomized trials, registries, surveys, and claims data. Effectiveness was estimated from the World-Wide Randomized Antibiotic Envelope Infection Prevention Trial. AEE was assumed to cost $953 per unit. The model projected mortality, quality-adjusted life-years, costs, and the incremental cost-effectiveness ratio of AEE use compared with usual care from a US healthcare sector perspective over a lifetime horizon. We assumed a cost-effectiveness threshold of $100 000 per quality-adjusted life-year gained. RESULTS: Compared with usual care, AEE use in initial implantations produced an incremental cost-effectiveness ratio of $112 000 per quality-adjusted life-year gained (39% probability of being cost-effective). In generator replacement procedures, AEE use produced an incremental cost-effectiveness ratio of $54 000 per quality-adjusted life-year gained (84% probability of being cost-effective). Results were sensitive to the underlying rate of infection, cost of the AEE, and durability of AEE effectiveness. CONCLUSIONS: Universal AEE use for cardiac implantable electronic device procedures in patients with heart failure with reduced ejection fraction is unlikely to be cost-effective, reinforcing the need for individualized risk assessment to guide uptake of the AEE in clinical practice. Selective use in patients at increased risk of infection, such as those undergoing generator replacement procedures, is more likely to meet health system value benchmarks.

Orthostatic Hypotension in Hypertensive Adults: Harry Goldblatt Award for Early Career Investigators 2021.

Orthostatic hypotension affects roughly 10% of individuals with hypertension and is associated with several adverse health outcomes, including dementia, cardiovascular disease, stroke, and death. Among adults with hypertension, orthostatic hypotension has also been shown to predict patterns of blood pressure dysregulation that may not be appreciated in the office setting, including nocturnal nondipping. Individuals with uncontrolled hypertension are at particular risk of orthostatic hypotension and may meet diagnostic criteria for the condition with a smaller relative reduction in blood pressure compared with normotensive individuals. Antihypertensive medications are commonly de-prescribed to address orthostatic hypotension; however, this approach may worsen supine or seated hypertension, which may be an important driver of adverse events in this population. There is significant variability between guidelines for the diagnosis of orthostatic hypotension with regards to timing and position of blood pressure measurements. Clinically relevant orthostatic hypotension may be missed when standing measurements are delayed or when taken after a seated rather than supine position. The treatment of orthostatic hypotension in patients with hypertension poses a significant management challenge for clinicians; however, recent evidence suggests that intensive blood pressure control may reduce the risk of orthostatic hypotension. A detailed characterization of blood pressure variability is essential to tailoring a treatment plan and can be accomplished using both in-office and out-of-office monitoring.

Cross-Sectional Relationships of Proximal Aortic Stiffness and Left Ventricular Diastolic Function in Adults in the Community.

Background Stiffness of the proximal aorta may play a critical role in adverse left ventricular (LV)-vascular interactions and associated LV diastolic dysfunction. In a community-based sample, we sought to determine the association between proximal aortic stiffness measured by cardiovascular magnetic resonance (CMR) and several clinical measures of LV diastolic mechanics. Methods and Results Framingham Heart Study Offspring adults (n=1502 participants, mean 67±9 years, 54% women) with available 1.5T CMR and transthoracic echocardiographic measures were included. Measures included proximal descending aortic strain and aortic arch pulse wave velocity by CMR (2002-2006) and diastolic function (mitral Doppler E and A wave velocity, E wave area, and LV tissue Doppler e' velocity) by echocardiography (2005-2008). Multivariable linear regression analysis was used to relate CMR aortic stiffness measures to measures of echocardiographic LV diastolic function. All continuous variables were standardized. In multivariable-adjusted regression analyses, aortic strain was inversely associated with E wave deceleration time (estimated ß=-0.10±0.032, P=0.001), whereas aortic arch pulse wave velocity was inversely associated with E/A ratio (estimated ß=-0.094±0.027, P=0.0006), E wave area (estimated ß=-0.070±0.027, P=0.010), and e' (estimated ß=-0.061±0.027, P=0.022), all indicating associations of higher aortic stiffness by CMR with less favorable LV diastolic function. Compared with men, women had a larger inverse relationship between pulse wave velocity and E/A ratio (interaction ß=-0.085±0.031, P=0.0064). There was no significant effect modification by age or a U-shaped (quadratic) relation between aortic stiffness and LV diastolic function measures. Conclusions Higher proximal aortic stiffness is associated with less favorable LV diastolic function. Future studies may clarify temporal relations of aortic stiffness with varying patterns and progression of LV diastolic dysfunction.

Wide Complex Tachycardia in a Young Woman.

A 27-year-old woman presented with palpitations and was found to have episodes of a non-sustained wide complex tachycardia. In this report, we discuss a differential diagnosis for the patient's wide complex tachycardia and the important ECG findings which lead to her diagnosis. (Level of Difficulty: Advanced.).

A Test in Context: Interpretation of High-Sensitivity Cardiac Troponin Assays in Different Clinical Settings.

High-sensitivity cardiac troponin (hs-cTn) assays have the ability to detect minute troponin concentrations and resolve minor changes in biomarker concentrations. Clinically, this allows for the ability to rapidly identify or exclude acute myocardial injury in the setting of acute chest discomfort-thus providing more rapid evaluation for acute myocardial infarction-but the improvements in troponin assays also create avenues for other applications where troponin release from the cardiomyocyte might confer prognostic information. These situations include cardiovascular risk assessment across a wide range of clinical circumstances, including apparently-well individuals, those at risk for heart disease, and those with prevalent cardiovascular disorders. The optimal hs-cTn threshold for each circumstance varies by the assay used and by the population assessed. This review will provide context for how hs-cTn assays might be interpreted depending on the application sought, reviewing results from studies leveraging hs-cTn for applications beyond "acute myocardial infarction diagnostic evaluation."

Racial/Ethnic Disparities in Hypertension Prevalence, Awareness, Treatment, and Control in the United States, 2013 to 2018.

[Figure: see text].

Gender Differences in Medicare Payments Among Cardiologists.

Importance: Women cardiologists receive lower salaries than men; however, it is unknown whether US Centers for Medicare & Medicaid Services (CMS) reimbursement also differs by gender and contributes to the lower salaries. Objective: To determine whether gender differences exist in the reimbursements, charges, and reimbursement per charge from CMS. Design, Setting, and Participants: This cross-sectional analysis used the CMS database to obtain 2016 reimbursement data for US cardiologists. These included reimbursements to cardiologists, charges submitted, and unique billing codes. Gender differences in reimbursement for evaluation and management and procedural charges from both inpatient and outpatient settings were also assessed. Analysis took place between April 2019 and December 2020. Main Outcomes and Measures: Outcomes included median CMS payments received and median charges submitted in the inpatient and outpatient settings in 2016. Results: In 2016, 17 524 cardiologists (2312 women [13%] and 15 212 men [87%]) received CMS payments in the inpatient setting, and 16 929 cardiologists (2151 women [13%] and 14 778 men [87%]) received CMS payments in the outpatient setting. Men received higher median payments in the inpatient (median [interquartile range], $62 897 [$30 904-$104 267] vs $45 288 [$21 371-$73 191]; P < .001) and outpatient (median [interquartile range], $91 053 [$34 820-$196 165] vs $51 975 [$15 622-$120 175]; P < .001) practice settings. Men submitted more median charges in the inpatient (median [interquartile range], 1190 [569-2093] charges vs 959 [569-2093] charges; P < .001) and outpatient settings (median [interquartile range], 1685 [644-3328] charges vs 870 [273-1988] charges; P < .001). In a multivariable-adjusted linear regression analysis, women received less CMS payments compared with men (log-scale ß = -0.06; 95% CI, -0.11 to -0.02) after adjustment for number of charges, number of unique billing codes, complexity of patient panel, years since graduation of physicians, and physician subspecialty. Payment by billing codes, both inpatient and outpatient, did not differ by gender. Conclusions and Relevance: There may be potential differences in CMS payments between men and women cardiologists, which appear to stem from gender differences in the number and types of charges submitted. The mechanisms behind these differences merit further research, both to understand why such gender differences exist and also to facilitate reductions in pay disparities.