Influenza vaccination and use of lipid lowering therapies in adults with atherosclerotic cardiovascular disease: An analysis of the Behavioral Risk Factor Surveillance System (BRFSS).

BACKGROUND: Influenza vaccination and lipid lowering therapy (LLT) are evidence-based interventions with substantial benefit for individuals with established atherosclerotic cardiovascular disease (ASCVD). However, levels of influenza immunization and LLT use are low, possibly due to pervasive fear-based misinformation uniquely targeting vaccines and LLT. Whether being unvaccinated for influenza predicts lower utilization of LLT is unknown. OBJECTIVES: We tested the hypothesis that American adults with ASCVD who are unvaccinated for influenza have lower use of LLT even after accounting for traditional factors associated with underuse of preventive therapies. METHODS: We pooled 2017, 2019, and 2021 survey data from the Behavioral Risk Factor Surveillance System (BRFSS), and selected respondents aged 40 to 75 years with self-reported ASCVD. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccination and self-reported LLT use. We performed a sensitivity analysis with multiple imputation to account for missing data. All analyses accounted for complex survey weighting. RESULTS: Of 66,923 participants with ASCVD, 55% reported influenza vaccination in the last year and 76% reported using LLT. Being unvaccinated for influenza was associated with lower odds of LLT use (OR 0.54; 95% CI 0.50, 0.58; P< .001). In a multivariable regression model adjusting for demographics and comorbidities, this association remained statistically significant (aOR 0.58, 95% CI 0.52, 0.64, P < .001). After additional adjustment for preventive care engagement, health care access, and use patterns of other cardiovascular medications this association persisted (aOR 0.66; 95% CI 0.60, 0.74; P < .001). There were no significant differences across subgroups, including those with and without hyperlipidemia. CONCLUSIONS: Unvaccinated status for influenza was independently associated with 34% lower odds of LLT use among American adults with ASCVD after adjustment for traditional factors linked to underuse of preventive therapies. This finding identifies a population with excess modifiable ASCVD risk, and supports investigation into nontraditional mechanisms driving underuse of preventive therapies, including fear-based misinformation.

A pragmatic clinical trial assessing the effect of a targeted notification and clinical support pathway on the diagnostic evaluation and treatment of individuals with left ventricular hypertrophy (NOTIFY-LVH).

BACKGROUND: Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting-but potentially unrecognized-LVH. METHODS: Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up. CONCLUSION: The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions. TRIAL REGISTRATION: NCT05713916.

Mortality and Heart Failure Hospitalization Among Young Adults With and Without Cardiogenic Shock After Acute Myocardial Infarction.

OBJECTIVES: To investigate risk factors and outcomes of cardiogenic shock complicating acute myocardial infarction (AMI-CS) in young patients with AMI. BACKGROUND: AMI-CS is associated with high morbidity and mortality rates. Data regarding AMI-CS in younger individuals are limited. METHODS AND RESULTS: Consecutive patients with type 1 AMI aged 18-50 years admitted to 2 large tertiary-care academic centers were included, and they were adjudicated as having cardiogenic shock (CS) by physician review of electronic medical records using the Society for Cardiovascular Angiography and Interventions CS classification system. Outcomes included all-cause mortality (ACM), cardiovascular mortality (CVM) and 1-year hospitalization for heart failure (HHF). In addition to using the full population, matching was also used to define a comparator group in the non-CS cohort. Among 2097 patients (mean age 44 ± 5.1 years, 74% white, 19% female), AMI-CS was present in 148 (7%). Independent risk factors of AMI-CS included ST-segment elevation myocardial infarction, left main disease, out-of-hospital cardiac arrest, female sex, peripheral vascular disease, and diabetes. Over median follow-up of 11.2 years, young patients with AMI-CS had a significantly higher risk of ACM (adjusted HR 2.84, 95% CI 1.68-4.81; P < 0.001), CVM (adjusted HR 4.01, 95% CI 2.17-7.71; P < 0.001), and 1-year HHF (adjusted HR 5.99, 95% CI 2.04-17.61; P = 0.001) compared with matched non-AMI-CS patients. Over the course of the study, there was an increase in the incidence of AMI-CS among young patients with MI as well as rising mortality rates for patients with both AMI-CS and non-AMI-CS. CONCLUSIONS: Of young patients with AMI, 7% developed AMI-CS, which was associated with a significantly elevated risk of mortality and HHF.

The current landscape of lipoprotein(a) in calcific aortic valvular disease.

PURPOSE OF REVIEW: Calcific aortic stenosis (CAVS) is the most common form of valvular heart disease in developed countries, increasing in prevalence with the aging population. Surgical or transcatheter aortic valve replacement is the only treatment available for CAVS. However, these interventions are typically reserved for severe symptomatic aortic stenosis (AS). The purpose of this review is to summarize the recent literature in uncovering the underlying pathophysiology of CAVS in the setting of lipoprotein (a) [Lp(a)] and emerging therapies targeting Lp(a) which may help halt disease progression in CAVS. RECENT FINDINGS: Pathophysiologic, epidemiological, and genetic studies over the past two decades have provided strong evidence that Lp(a) is an important mediator of calcific aortic valvular disease (CAVD). Studies suggest that Lp(a) is a key carrier of pro-calcifying oxidized phospholipids (OxPL). The metabolism of OxPL results in a pro-inflammatory state and subsequent valvular thickening and mineralization through pro-osteogenic signaling. The identification of Lp(a) as a causal mediator of CAVD has allowed for opportunities for emerging therapeutic agents which may slow the progression of CAVD (Fig. 1JOURNAL/cocar/04.03/00001573-202109000-00007/figure1/v/2021-08-04T080204Z/r/image-jpeg). SUMMARY: This review summarizes the current knowledge on the association of Lp(a) with CAVD and ongoing studies of potential Lp(a)-lowering therapies. Based on the rate-limiting and causal role of Lp(a) in progression of CAVS, these therapies may represent novel pharmacotherapies in AS and inform the developing role of Lp(a) in the clinical management of CAVD.

Women who experience a myocardial infarction at a young age have worse outcomes compared with men: the Mass General Brigham YOUNG-MI registry.

AIMS: There are sex differences in presentation, treatment, and outcomes of myocardial infarction (MI) but less is known about these differences in a younger patient population. The objective of this study was to investigate sex differences among individuals who experience their first MI at a young age. METHODS AND RESULTS: Consecutive patients presenting to two large academic medical centres with a Type 1 MI at ≤50 years of age between 2000 and 2016 were included. Cause of death was adjudicated using electronic health records and death certificates. In total, 2097 individuals (404 female, 19%) had an MI (mean age 44 ± 5.1 years, 73% white). Risk factor profiles were similar between men and women, although women were more likely to have diabetes (23.7% vs. 18.9%, P = 0.028). Women were less likely to undergo invasive coronary angiography (93.5% vs. 96.7%, P = 0.003) and coronary revascularization (82.1% vs. 92.6%, P < 0.001). Women were significantly more likely to have MI with non-obstructive coronary disease on angiography (10.2% vs. 4.2%, P < 0.001). They were less likely to be discharged with aspirin (92.2% vs. 95.0%, P = 0.027), beta-blockers (86.6% vs. 90.3%, P = 0.033), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (53.4% vs. 63.7%, P < 0.001), and statins (82.4% vs. 88.4%, P < 0.001). There was no significant difference in in-hospital mortality; however, women who survived to hospital discharge experienced a higher all-cause mortality rate (adjusted HR = 1.63, P = 0.01; median follow-up 11.2 years) with no significant difference in cardiovascular mortality (adjusted HR = 1.14, P = 0.61). CONCLUSIONS: Women who experienced their first MI under the age of 50 were less likely to undergo coronary revascularization or be treated with guideline-directed medical therapies. Women who survived hospitalization experienced similar cardiovascular mortality with significantly higher all-cause mortality than men. A better understanding of the mechanisms underlying these differences is warranted.

Recent trends in acute myocardial infarction among the young.

PURPOSE OF REVIEW: In recent decades, the incidence of myocardial infarction (MI) has declined among the general population. However, MI rates in the young have not decreased as much as has been observed among older individuals. This review will focus on recent trends of MI in young patients, factors that may account for these trends, and implications for future prevention. RECENT FINDINGS: MI rates in young patients, particularly in women, have not decreased in the same fashion as they have for their older counterparts, with some studies reporting an increase. The reasons for these findings include underestimation of cardiovascular risk, and accordingly treatment, in the young, as well as an increasing prevalence of risk factors such as obesity and diabetes. SUMMARY: Better recognition and treatment of cardiovascular risk factors among young adults may improve outcomes. There is a need for improved methods to assess and treat cardiovascular risk in young individuals.

Current and future role of lipoprotein(a) in preventive cardiology.

PURPOSE OF REVIEW: The purpose of this review is to highlight our emerging understanding of lipoprotein(a) [Lp(a)]'s role in atherosclerotic cardiovascular disease (ASCVD), its structure-function relationship, and promising developments within the therapeutic pipeline. RECENT FINDINGS: Elevated levels of Lp(a) are strongly associated with an increased risk of coronary heart disease, calcific aortic valve stenosis, and ischemic stroke. With circulating levels almost exclusively genetically mediated, increased levels of Lp(a) contribute significantly to the residual cardiovascular disease risk in individuals with otherwise well controlled risk factors. The unique structure of Lp(a) - comprised of a genetically heterogeneous apolipoprotein(a) molecule bound to an LDL-like moiety - provides insight into its pathogenic role in cardiovascular disease and also complicates its accurate measurement. Emerging therapies targeting the apolipoprotein(a) component of Lp(a) have the potential to revolutionize the management of individuals with elevated Lp(a). SUMMARY: With promising therapies on the horizon, there has been a renewed focus on the role of Lp(a) in ASCVD. Given Lp(a)'s strong and independent association with key cardiovascular outcomes, it is hopeful that these promising targeted therapies will add another therapeutic option for the prevention of cardiovascular disease.

Optimizing Dyslipidemia Management for the Prevention of Cardiovascular Disease: a Focus on Risk Assessment and Therapeutic Options.

Primary prevention of incident atherosclerotic cardiovascular disease (ASCVD) as well as decreasing the risk of future events in those with established atherosclerosis is critical from a public health perspective. Management of dyslipidemias constitutes a key target in decreasing the risk of developing ASCVD events. While there have been great strides in the treatment of dyslipidemia over the last three decades, there are important recent developments and ongoing research that will expand the available therapeutic options and enable further cardiovascular risk reduction. PURPOSE OF REVIEW: The purpose of this paper is to review new developments relating to the primary prevention and management of ASCVD with a specific focus on optimizing the treatment of dyslipidemias. RECENT FINDINGS: In the realm of ASCVD risk prediction, mounting evidence over the last decade has demonstrated that coronary artery calcium testing is superior to any serum biomarker in the prediction of future ASCVD events and in discriminating future cardiovascular risk. As such, it has been incorporated into the most recent ACC/AHA primary prevention guideline to help guide management decisions in select patients. In terms of the management of dyslipidemias, PCSK9 inhibitors lower LDL-C by 50-70% and provide an additional 15% reduction in key cardiovascular events in high-risk patients with known ASCVD, as demonstrated in the ODYSSEY and FOURIER trials. Cholesteryl ester transfer protein (CETP) inhibitors, which significantly increase HDL-C levels, demonstrated mixed results in large clinical trials and have helped reframe HDL-C as a risk marker rather than a modifiable risk factor. In regard to the management of triglycerides, the REDUCE-IT trial demonstrated a nearly 5% absolute reduction in key cardiovascular events with a highly purified fish-oil derivative named icosapent ethyl in high-risk patients already on statin therapy. Finally, in regard to lipoprotein(a)-which is a strong risk factor for ASCVD-there are exciting developments in the therapeutic pipeline which reduce circulating lipoprotein(a) levels by nearly 90%. The management of dyslipidemias continues to be an exciting field with several ongoing cardiovascular outcomes trials, improvement in risk prediction models, and new therapeutic agents in the pipeline that will further mitigate residual cardiovascular risk in both primary and secondary prevention patients.

Statin Twitter: Human and Automated Bot Contributions, 2010 to 2022.

BACKGROUND: Many individuals eligible for statin therapy decline treatment, often due to fear of adverse effects. Misinformation about statins is common and drives statin reluctance, but its prevalence on social media platforms, such as Twitter (now X) remains unclear. Social media bots are known to proliferate medical misinformation, but their involvement in statin-related discourse is unknown. This study examined temporal trends in volume, author type (bot or human), and sentiment of statin-related Twitter posts (tweets). METHODS AND RESULTS: We analyzed original tweets with statin-related terms from 2010 to 2022 using a machine learning-derived classifier to determine the author's bot probability, natural language processing to assign each tweet a negative or positive sentiment, and manual qualitative analysis to identify statin skepticism in a random sample of all tweets and in highly influential tweets. We identified 1 155 735 original statin-related tweets. Bots produced 333 689 (28.9%), humans produced 699 876 (60.6%), and intermediate probability accounts produced 104 966 (9.1%). Over time, the proportion of bot tweets decreased from 47.8% to 11.3%, and human tweets increased from 43.6% to 79.8%. The proportion of negative-sentiment tweets increased from 27.8% to 43.4% for bots and 30.9% to 38.4% for humans. Manually coded statin skepticism increased from 8.0% to 19.0% for bots and from 26.0% to 40.0% for humans. CONCLUSIONS: Over the past decade, humans have overtaken bots as generators of statin-related content on Twitter. Negative sentiment and statin skepticism have increased across all user types. Twitter may be an important forum to combat statin-related misinformation.

Artificial Intelligence in Coronary Artery Calcium Scoring Detection and Quantification.

Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such "incidental" CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.

Lipoprotein(a): Emerging insights and therapeutics.

The strong association between lipoprotein (a) [Lp(a)] and atherosclerotic cardiovascular disease has led to considerations of Lp(a) being a potential target for mitigating residual cardiovascular risk. While approximately 20 % of the population has an Lp(a) level greater than 50 mg/dL, there are no currently available pharmacological lipid-lowering therapies that have demonstrated substantial reduction in Lp(a). Novel therapies to lower Lp(a) include antisense oligonucleotides and small-interfering ribonucleic acid molecules and have shown promising results in phase 2 trials. Phase 3 trials are currently underway and will test the causal relationship between Lp(a) and ASCVD and whether lowering Lp(a) reduces cardiovascular outcomes. In this review, we summarize emerging insights related to Lp(a)'s role as a risk-enhancing factor for ASCVD, association with calcific aortic stenosis, effects of existing therapies on Lp(a) levels, and variations amongst patient populations. The evolving therapeutic landscape of emerging therapeutics is further discussed.

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

BACKGROUND: Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). CONCLUSIONS: Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease.

BACKGROUND: Lipoprotein(a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether the optimal Lp(a) threshold for risk assessment should differ based on baseline ASCVD status is unknown. OBJECTIVES: The purpose of this study was to assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without baseline ASCVD. METHODS: We studied a retrospective cohort of patients with Lp(a) measured at 2 medical centers in Boston, Massachusetts, from 2000 to 2019. To assess the association of Lp(a) with incident MACE (nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or cardiovascular mortality), Lp(a) percentile groups were generated with the reference group set at the first to 50th Lp(a) percentiles. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE. RESULTS: Overall, 16,419 individuals were analyzed with a median follow-up of 11.9 years. Among the 10,181 (62%) patients with baseline ASCVD, individuals in the 71st to 90th percentile group had a 21% increased hazard of MACE (adjusted HR: 1.21; P < 0.001), which was similar to that of individuals in the 91st to 100th group (adjusted HR: 1.26; P < 0.001). Among the 6,238 individuals without established ASCVD, there was a continuously higher hazard of MACE with increasing Lp(a), and individuals in the 91st to 100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (P < 0.001). CONCLUSIONS: In a large, contemporary U.S. cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the threshold for risk assessment may be different in primary vs secondary prevention cohorts.

Improving guideline-based anticoagulation in atrial fibrillation: A systematic literature review of prospective trials.

BACKGROUND: Guidelines for anticoagulation in patients with atrial fibrillation (AF) aim to decrease the risk of ischemic stroke. However, there is a gap in actual practice between patients who have an indication for anticoagulation and those who are actually prescribed anticoagulation. OBJECTIVE: We sought to evaluate the efficacy of prior population-based interventions aimed at decreasing this AF anticoagulation gap. METHODS: This study was prospectively registered in the International Prospective Register of Systematic Reviews database (CRD42021287875). A systematic literature review was conducted to obtain all prospective individually randomized and cluster randomized trials by searching 4 electronic databases: PubMed, Google Scholar, Web of Science, and Medline. RESULTS: After a review of 1474 studies, 20 trials were included in this systematic literature review. Forty-five percent were effective in decreasing the AF anticoagulation gap. Trial interventions that improved anticoagulation prescribing included 6 trials of electronic risk assessment or decision support, 1 trial of provider education, 2 trials of new protocol or pathway, and 2 trials of patient education. Six of 15 ambulatory trials, 2 of 4 inpatient trials, and 1 trial that spanned inpatient and outpatient settings improved anticoagulation prescribing rates. Interventions focused on patient education, provider education, and electronic risk assessment or decision support increased absolute appropriate anticoagulation prescribing by 8.3%, 4.9%, and 2.0%, respectively. CONCLUSION: Interventions aimed at improving anticoagulation prescribing patterns in AF can be effective, although there is heterogeneity in outcomes across intervention type. The most effective interventions appeared to target patient education, provider education, and electronic risk assessment or decision support.

Race, ethnicity, sex, and socioeconomic disparities in anticoagulation for atrial fibrillation: A narrative review of contemporary literature.

Atrial fibrillation (AF) is the most prevalent arrhythmia in the United States and is responsible for 1 in 7 ischemic strokes. While anticoagulation is effective at preventing strokes, prior work has highlighted significant disparities in anticoagulation prescribing. Furthermore, racial, ethnic, sex, and socioeconomic disparities in AF outcomes have been described. As such, we aimed to review recent data on disparities with respect to anticoagulation for AF published between January 2018 and February 2021. The search string consisted of 7 phrases that combined AF, anticoagulation, and disparities involving sex, race, ethnicity, income, socioeconomic status (SES), and access to care and identified 13 relevant articles. The aggregate data demonstrated that Black patients were less likely to be prescribed anticoagulation than patients of other racial/ethnic groups. Additionally, Black patients were more likely to be prescribed warfarin instead of direct oral anticoagulants (DOACs) despite evidence that DOACs are safer and better tolerated. Lower-income patients and patients with less education were also less likely to receive DOACs. Some studies found that women were less likely to be anticoagulated than men even when their estimated stroke risk was higher, although other studies did not show sex-based differences. Building upon prior work, our study demonstrates that racial and ethnic disparities have persisted in the management of AF. Additionally, we our work highlights that there are significant disparities in anticoagulation management for AF associated with sex, income, and education. More work is needed to identify mechanisms for these disparities and identify potential solutions to achieve pharmacoequity.

Association between implanted cardioverter-defibrillators and mortality for patients with left ventricular ejection fraction between 30% and 35.

BACKGROUND: Consensus guidelines support the use of implanted cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death in patients with either non-ischaemic or ischaemic cardiomyopathy with left ventricular ejection fraction (LVEF) ≤35%. However, evidence from trials for efficacy specifically for patients with LVEF near 35% is weak. Past trials are underpowered for this population and future trials are unlikely to be performed. METHODS: Patients with lowest LVEF between 30% and 35% without an ICD prior to the lowest-LVEF echo (defined as 'time zero') were identified by querying echocardiography data from 28 November 2001 to 9 July 2020 at the Massachusetts General Hospital linked to ICD treatment status. To assess the association between ICD and mortality, propensity score matching followed by Cox proportional hazards models considering treatment status as a time-dependent covariate was used. A secondary analysis was performed for LVEF 36%-40%. RESULTS: Initially, 526 440 echocardiograms representing 266 601 unique patients were identified. After inclusion and exclusion criteria were applied, 6109 patients remained for the analytical cohort. In bivariate unadjusted comparisons, patients who received ICDs were substantially more often male (79.8% vs 65.4%, p<0.0001), more often white (87.5% vs 83.7%, p<0.046) and more often had a history of ventricular tachycardia (74.5% vs 19.1%, p<0.0001) and myocardial infarction (56.1% vs 38.2%, p<0.0001). In the propensity matched sample, after accounting for time-dependence, there was no association between ICD and mortality (HR 0.93, 95% CI 0.75 to 1.15, p=0.482). CONCLUSIONS: ICD therapy was not associated with reduced mortality near the conventional LVEF threshold of 35%. Although this treatment design cannot definitively demonstrate lack of efficacy, our results are concordant with available prior trial data. A definitive, well-powered trial is needed to answer the important clinical question of primary prevention ICD efficacy between LVEF 30% and 35%.

Natural Language Processing for the Ascertainment and Phenotyping of Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy on Echocardiogram Reports.

Extracting and accurately phenotyping electronic health documentation is critical for medical research and clinical care. We sought to develop a highly accurate and open-source natural language processing (NLP) module to ascertain and phenotype left ventricular hypertrophy (LVH) and hypertrophic cardiomyopathy (HCM) diagnoses from echocardiogram reports within a diverse hospital network. After the initial development on 17,250 echocardiogram reports, 700 unique reports from 6 hospitals were randomly selected from data repositories within the Mass General Brigham healthcare system and manually adjudicated by physicians for 10 subtypes of LVH and diagnoses of HCM. Using an open-source NLP system, the module was formally tested on 300 training set reports and validated on 400 reports. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the discriminative accuracy of the NLP module. The NLP demonstrated robust performance across the 10 LVH subtypes, with the overall sensitivity and specificity exceeding 96%. In addition, the NLP module demonstrated excellent performance in detecting HCM diagnoses, with sensitivity and specificity exceeding 93%. In conclusion, we designed a highly accurate NLP module to determine the presence of LVH and HCM on echocardiogram reports. Our work demonstrates the feasibility and accuracy of NLP to detect diagnoses on imaging reports, even when described in free text. This module has been placed in the public domain to advance research, trial recruitment, and population health management for patients with LVH-associated conditions.

Cardiovascular outcomes in patients with coronary artery disease and elevated lipoprotein(a): implications for the OCEAN(a)-outcomes trial population.

Aims: The ongoing Olpasiran Trials of Cardiovascular Events and Lipoprotein(a) Reduction [OCEAN(a)]-Outcomes trial is evaluating whether Lp(a) lowering can reduce the incidence of cardiovascular events among patients with prior myocardial infarction (MI) or percutaneous coronary intervention (PCI) and elevated Lp(a) (≥200 nmol/L). The purpose of this study is to evaluate the association of elevated Lp(a) with cardiovascular outcomes in an observational cohort resembling the OCEAN(a)-Outcomes trial main enrolment criteria. Methods and results: This study included patients aged 18-85 years with Lp(a) measured as part of their clinical care between 2000 and 2019. While patients were required to have a history of MI, or PCI, those with severe kidney dysfunction or a malignant neoplasm were excluded. Elevated Lp(a) was defined as ≥200 nmol/L consistent with the OCEAN(a)-Outcomes trial. The primary outcome was a composite of coronary heart disease death, MI, or coronary revascularization. Natural language processing algorithms, billing and ICD codes, and laboratory data were employed to identify outcomes and covariates. A total of 3142 patients met the eligibility criteria, the median age was 61 (IQR: 52-73) years, 28.6% were women, and 12.3% had elevated Lp(a). Over a median follow-up of 12.2 years (IQR: 6.2-14.3), the primary composite outcome occurred more frequently in patients with versus without elevated Lp(a) [46.0 vs. 38.0%, unadjHR = 1.30 (95% CI: 1.09-1.53), P = 0.003]. Following adjustment for measured confounders, elevated Lp(a) remained independently associated with the primary outcome [adjHR = 1.33 (95% CI: 1.12-1.58), P = 0.001]. Conclusion: In an observational cohort resembling the main OCEAN(a)-Outcomes Trial enrolment criteria, patients with an Lp(a) ≥200 nmol/L had a higher risk of cardiovascular outcomes.

Impact of coronary artery calcium testing on patient management.

BACKGROUND: Coronary artery calcium (CAC) scoring can identify individuals who may benefit from aggressive prevention therapies. However, there is a paucity of contemporary data on the impact of CAC testing on patient management. METHODS: Retrospective cohort study of adults who underwent CAC testing at Brigham and Women's Hospital between 2015 and 2019. Information on baseline medications, follow-up medications, lifestyle modification, and downstream cardiovascular testing within one-year post-CAC were obtained from electronic health records. RESULTS: Of the 839 patients with available baseline and follow-up data, 376 (45%) had a CAC â€‹= â€‹0, 289 (34%) had CAC â€‹= â€‹1-99, and 174 (21%) had CAC≥100. The mean age at time of CAC testing was 59 â€‹± â€‹9.7 years. Patients with higher CAC scores were more likely to be male, have diabetes and hypertension, and have higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol. A non-zero CAC score was associated with initiation of aspirin (41% increase, p â€‹< â€‹0.001), anti-hypertensives (9% increase, p â€‹= â€‹0.031), and lipid-lowering therapies (114% increase, p â€‹< â€‹0.001), whereas CAC â€‹= â€‹0 was not. Among individuals with CAC≥100, 75% were started on new or more intense lipid-lowering therapy. Higher calcium scores correlated with increased physician recommendations for diet (p â€‹= â€‹0.008) and exercise (p â€‹= â€‹0.004). The proportion of cardiovascular downstream testing following CAC was 9.1%, and the majority of patients who underwent additional testing post-CAC had CAC scores ≥100. CONCLUSION: Approximately half of individuals referred for CAC testing had evidence of calcified coronary plaque, and of those who had significant calcifications (CAC≥100), nearly 90% were prescribed lipid-lowering therapies post-CAC. Rates of downstream non-invasive testing were low and such testing was mostly performed in patients who had at least moderate CAC.

Association of inflammatory disease and long-term outcomes among young adults with myocardial infarction: the Mass General Brigham YOUNG-MI Registry.

AIMS: Autoimmune systemic inflammatory diseases (SIDs) are associated with an increased risk of cardiovascular (CV) disease, particularly myocardial infarction (MI). However, there are limited data on the prevalence and effects of SID among adults who experience an MI at a young age. We sought to determine the prevalence and prognostic implications of SID among adults who experienced an MI at a young age. METHODS AND RESULTS: The YOUNG-MI registry is a retrospective cohort study from two large academic centres, which includes patients who experienced a first MI at 50 years of age or younger. SID was ascertained through physician review of the electronic medical record (EMR). Incidence of death was ascertained through the EMR and national databases. The cohort consisted of 2097 individuals, with 53 (2.5%) possessing a diagnosis of SID. Patients with SID were more likely to be female (36% vs. 19%, P = 0.004) and have hypertension (62% vs. 46%, P = 0.025). Over a median follow-up of 11.2 years, patients with SID experienced an higher risk of all-cause mortality compared with either the full cohort of non-SID patients [hazard ratio (HR) = 1.95, 95% confidence interval (CI) (1.07-3.57), P = 0.030], or a matched cohort based on age, gender, and CV risk factors [HR = 2.68, 95% CI (1.18-6.07), P = 0.018]. CONCLUSIONS: Among patients who experienced a first MI at a young age, 2.5% had evidence of SID, and these individuals had higher rates of long-term all-cause mortality. Our findings suggest that the presence of SID is associated with worse long-term survival after premature MI.