Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.

Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. METHODS: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. FINDINGS: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. INTERPRETATION: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. FUNDING: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

Low-Density Lipoprotein Cholesterol Is Predominantly Associated With Atherosclerotic Cardiovascular Disease Events in Patients With Evidence of Coronary Atherosclerosis: The Western Denmark Heart Registry.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. METHODS: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute-funded Multi-Ethnic Study of Atherosclerosis. RESULTS: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level (>193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Prognostic value of myocardial flow reserve vs corrected myocardial flow reserve in patients without obstructive coronary artery disease.

BACKGROUND: Myocardial flow reserve (MFR) by positron emission tomography (PET) is a validated measure of cardiovascular risk. Elevated resting rate pressure product (RPP = heart rate x systolic blood pressure) can cause high resting myocardial blood flow (MBF), resulting in reduced MFR despite normal/near-normal peak stress MBF. When resting MBF is high, it is not known if RPP-corrected MFR (MFRcorrected) helps reclassify CV risk. We aimed to study this question in patients without obstructive coronary artery disease (CAD). METHODS: We retrospectively studied patients referred for rest/stress cardiac PET at our center from 2006 to 2020. Patients with abnormal perfusion (summed stress score >3) or prior coronary artery bypass grafting (CABG) were excluded. MFRcorrected was defined as stress MBF/corrected rest MBF where corrected rest MBF = rest MBF x 10,000/RPP. The primary outcome was major cardiovascular events (MACE): cardiovascular death or myocardial infarction. Associations of MFR and MFRcorrected with MACE were assessed using unadjusted and adjusted Cox regression. RESULTS: 3276 patients were followed for a median of 7 (IQR 3-12) years. 1685 patients (51%) had MFR <2.0, and of those 366 (22%) had an MFR ≥2.0 after RPP correction. MFR <2.0 was associated with an increased absolute risk of MACE (HR 2.24 [1.79-2.81], P < 0.0001). Among patients with MFR <2.0, the risk of MACE was not statistically different between patients with an MFRcorrected ≥2.0 compared with those with MFRcorrected <2.0 (1.9% vs 2.3% MACE/year, HR 0.84 [0.63-1.13], P = 0.26) even after adjustment for confounders (P = 0.66). CONCLUSIONS: In patients without overt obstructive CAD and MFR< 2.0, there was no significant difference in cardiovascular risk between patients with discordant (≥2.0) and concordant (<2) MFR following RPP correction. This suggests that RPP-corrected MFR may not consistently provide accurate risk stratification in patients with normal perfusion and MFR <2.0. Stress MBF and uncorrected MFR should be reported to more reliably convey cardiovascular risk beyond perfusion results.

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.

Targeting pharmacotherapies for inflammatory and cardiorenal endpoints in kidney disease.

ABSTRACT: Inflammation is an important contributor to excess cardiovascular risk and progressive renal injury in people with CKD. Dysregulation of the innate and adaptive immune system is accelerated by CKD and results in increased systemic inflammation, a heightened local vascular inflammatory response leading to accelerated atherosclerosis, and dysfunction of the cardiac and renal endothelium and microcirculation. Understanding and addressing the dysregulated immune system is a promising approach to modifying cardiorenal outcomes in people with CKD. However, targeted pharmacotherapies adopted from trials of non-CKD and cardio-rheumatology populations are only beginning to be developed and tested in human clinical trials. Pharmacotherapies that inhibit activation of the NLRP3 inflammasome and the downstream cytokines IL-1 and IL-6 are the most well-studied. However, most of the available evidence for efficacy is from small clinical trials with inflammatory and cardiorenal biomarker endpoints, rather than cardiovascular event endpoints, or from small CKD subgroups in larger clinical trials. Other pharmacotherapies that have proven beneficial for cardiorenal endpoints in people with CKD have been found to have pleiotropic anti-inflammatory benefits including statins, mineralocorticoid receptor antagonists, SGLT-2 inhibitors, and GLP-1 agonists. Finally, emerging therapies in CKD such as IL-6 inhibition, small-interfering RNA against lipoproteins, AhR inhibitors, and therapies adopted from the renal transplant population including mTOR inhibitors and T regulatory cell promoters may have benefits for cardiorenal and inflammatory endpoints but require further investigation in clinical trials.

ACC/AHA/ASE/ASNC/ASPC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2023 Multimodality Appropriate Use Criteria for the Detection and Risk Assessment of Chronic Coronary Disease.

The American College of Cardiology (ACC) Foundation, along with key specialty and subspecialty societies, conducted an appropriate use review of stress testing and anatomic diagnostic procedures for risk assessment and evaluation of known or suspected chronic coronary disease (CCD), formerly referred to as stable ischemic heart disease (SIHD). This document reflects an updating of the prior Appropriate Use Criteria (AUC) published for radionuclide imaging, stress echocardiography (echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for SIHD. This is in keeping with the commitment to revise and refine the AUC on a frequent basis. As with the prior version of this document, rating of test modalities is provided side-by-side for a given clinical scenario. These ratings are explicitly not considered competitive rankings due to the limited availability of comparative evidence, patient variability, and the range of capabilities available in any given local setting1-4.This version of the AUC for CCD is a focused update of the prior version of the AUC for SIHD4. Key changes beyond the updated ratings based on new evidence include the following: 1. Clinical scenarios related to preoperative testing were removed and will be incorporated into another AUC document under development. 2. Some clinical scenarios and tables were removed in an effort to simplify the selection of clinical scenarios. Additionally, the flowchart of tables has been reorganized, and all clinical scenario tables can now be reached by answering a limited number of clinical questions about the patient, starting with the patient's symptom status. 3. Several clinical scenarios have been revised to incorporate changes in other documents such as pretest probability assessment, atherosclerotic cardiovascular disease (ASCVD) risk assessment, syncope, and others. ASCVD risk factors that are not accounted for in contemporary risk calculators have been added as modifiers to certain clinical scenarios. The 64 clinical scenarios rated in this document are limited to the detection and risk assessment of CCD and were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines.5 These clinical scenarios do not specifically address patients having acute chest pain episodes. They may, however, be applicable in the inpatient setting if the patient is not having an acute coronary syndrome and warrants evaluation for CCD.Using standardized methodology, clinical scenarios were developed to describe common patient encounters in clinical practice focused on common applications and anticipated uses of testing for CCD. Where appropriate, the scenarios were developed on the basis of the most current ACC/American Heart Association guidelines. A separate, independent rating panel scored the clinical scenarios in this document on a scale of 1 to 9, following a modified Delphi process consistent with the recently updated AUC development methodology. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented, midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is rarely appropriate.

Frequency, compliance, and yield of cardiac testing after high-sensitivity troponin accelerated diagnostic protocol implementation.

BACKGROUND: Among persons presenting to the emergency department with suspected acute myocardial infarction (MI), cardiac troponin (cTn) testing is commonly used to detect acute myocardial injury. Accelerated diagnostic protocols (ADPs) guide clinicians to integrate cTn results with other clinical information to decide whether to order further diagnostic testing. OBJECTIVE: To determine the change in the rate and yield of stress test or coronary CT angiogram following cTn measurement in patients with chest pain presenting to the emergency department pre- and post-transition to a high-sensitivity (hs-cTn) assay in an updated ADP. METHODS: Using electronic health records, we examined visits for chest pain at five emergency departments affiliated with an integrated academic health system 1-year pre- and post-hs-cTn assay transition. Outcomes included stress test or coronary imaging frequency, ADP compliance among those with additional testing, and diagnostic yield (ratio of positive tests to total tests). RESULTS: There were 7564 patient-visits for chest pain, including 3665 in the pre- and 3899 in the post-period. Following the updated ADP using hs-cTn, 862 (23.5 per 100 patient visits) visits led to subsequent testing versus 1085 (27.8 per 100 patient visits) in the pre-hs-cTn period, (P < 0.001). Among those who were tested, the protocol-compliant rate fell from 80.9% to 46.5% (P < 0.001), but the yield of those tests rose from 24.5% to 29.2% (P = 0.07). Among tests that were noncompliant with ADP guidance, yield was similar pre- and post-updated hs-cTn ADP implementation (pre 13.0%, post 15.4% (P = 0.43). CONCLUSION: Implementation of hs-cTn supported by an updated ADP was associated with a lower rate of stress testing and coronary CT angiogram.

Low educational attainment is associated with higher all-cause and cardiovascular mortality in the United States adult population.

INTRODUCTION: Educational attainment is an important social determinant of health (SDOH) for cardiovascular disease (CVD). However, the association between educational attainment and all-cause and CVD mortality has not been longitudinally evaluated on a population-level in the US, especially in individuals with atherosclerotic cardiovascular disease (ASCVD). In this nationally representative study, we assessed the association between educational attainment and the risk of all-cause and cardiovascular (CVD) mortality in the general adult population and in adults with ASCVD in the US. METHODS: We used data from the 2006-2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated age-adjusted mortality rates (AAMR) by levels of educational attainment (< high school (HS), HS/General Education Development (GED), some college, and ≥ College) in the overall population and in adults with ASCVD. Cox proportional hazards models were used to examine the multivariable-adjusted associations between educational attainment and all-cause and CVD mortality. RESULTS: The sample comprised 210,853 participants (mean age 46.3), representing ~ 189 million adults annually, of which 8% had ASCVD. Overall, 14.7%, 27%, 20.3%, and 38% of the population had educational attainment < HS, HS/GED, Some College, and ≥ College, respectively. During a median follow-up of 4.5 years, all-cause age-adjusted mortality rates were 400.6 vs. 208.6 and 1446.7 vs. 984.0 for the total and ASCVD populations for < HS vs ≥ College education, respectively. CVD age adjusted mortality rates were 82.1 vs. 38.7 and 456.4 vs 279.5 for the total and ASCVD populations for < HS vs ≥ College education, respectively. In models adjusting for demographics and SDOH, < HS (reference = ≥ College) was associated with 40-50% increased risk of mortality in the total population and 20-40% increased risk of mortality in the ASCVD population, for both all-cause and CVD mortality. Further adjustment for traditional risk factors attenuated the associations but remained statistically significant for < HS in the overall population. Similar trends were seen across sociodemographic subgroups including age, sex, race/ethnicity, income, and insurance status. CONCLUSIONS: Lower educational attainment is independently associated with increased risk of all-cause and CVD mortality in both the total and ASCVD populations, with the highest risk observed for individuals with < HS education. Future efforts to understand persistent disparities in CVD and all-cause mortality should pay close attention to the role of education, and include educational attainment as an independent predictor in mortality risk prediction algorithms.

[Imaging diagnostics of cardiac sarcoidosis]. / Bildgebende Diagnostik der kardialen Sarkoidose.

Cardiac involvement is clinically apparent in approximately 5% of all patients with systemic sarcoidosis, whereas evidence of cardiac involvement by imaging studies can be found in approximately 20% of cases. Occasionally, isolated cardiac sarcoidosis is encountered and is the only sign of the disease. The most frequent cardiac manifestations of the multifocal granulomatous inflammation include atrioventricular (AV) blocks and other conduction disorders, ventricular arrhythmias, sudden cardiac death and left and right ventricular wall disorders. Accordingly, symptoms that should raise suspicion include palpitations, lightheadedness and syncope. The diagnostic approach to cardiac sarcoidosis is not straightforward. Typical echocardiographic findings include regional thinning and contraction abnormalities particularly in basal, septal and lateral locations. Infrequently, myocardial hypertrophy may be present; however, the sensitivity of echocardiography is low and cardiac sarcoidosis can be present even when an echocardiogram is unrevealing. Cardiac magnetic resonance imaging (MRI) frequently shows late gadolinium enhancement (LGE) in a multifocal pattern often involving the basal septum and lateral walls. The sensitivity and specificity of MRI for detecting cardiac sarcoidosis are high. Fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in the diagnostic algorithm due to its ability to visualize focal inflammatory activity both in the myocardium and in extracardiac locations. This may help target the optimal location for biopsy in order to obtain histologic proof of sarcoidosis and can also be used to follow the response to anti-inflammatory treatment. Notably, the sensitivity of endomyocardial biopsy is poor due to the patchy nature of myocardial involvement. In clinical practice, either histologic evidence of noncaseating granulomas from the myocardium or evidence from extracardiac tissue in combination with typical cardiac imaging findings are required to establish the diagnosis.

The Role of Imaging in Preventive Cardiology in Women.

PURPOSE OF REVIEW: The prevalence of CVD in women is increasing and is due to the increased prevalence of CV risk factors. Traditional CV risk assessment tools for prevention have failed to accurately determine CVD risk in women. CAC has shown to more precisely determine CV risk and is a better predictor of CV outcomes. Coronary CTA provides an opportunity to determine the presence of CAD and initiate prevention in women presenting with angina. Identifying women with INOCA due to CMD with use of cPET or cMRI with MBFR is vital in managing these patients. This review article outlines the role of imaging in preventive cardiology for women and will include the latest evidence supporting the use of these imaging tests for this purpose. RECENT FINDINGS: CV mortality is higher in women who have more extensive CAC burden. Women have a greater prevalence of INOCA which is associated with higher MACE. INOCA is due to CMD in most cases which is associated with traditional CVD risk factors. Over half of these women are untreated or undertreated. Recent study showed that stratified medical therapy, tailored to the specific INOCA endotype, is feasible and improves angina in women. Coronary CTA is useful in the setting of women presenting with acute chest pain to identify CAD and initiate preventive therapy. CAC confers greater relative risk for CV mortality in women versus (vs.) men. cMRI or cPET is useful to assess MBFR to diagnose CMD and is another useful imaging tool in women for CV prevention.

Low coronary flow relative to myocardial mass predicts heart failure in symptomatic hypertensive patients with no obstructive coronary artery disease.

AIMS: The transition from hypertension to heart failure (HF) remains poorly understood. We hypothesized that insufficient perfusion to match global metabolic demand, reflected by a low ratio of myocardial blood flow to global myocardial mass, may be a HF risk marker. METHODS AND RESULTS: A retrospective cohort (n = 346) of patients with hypertension who underwent clinical positron emission tomography (PET) myocardial perfusion imaging for chest pain and/or dyspnoea at Brigham and Women's Hospital (Boston, MA, USA) were studied. Patients without obstructive coronary artery disease by history or PET perfusion (summed stress score <3), HF, cardiomyopathy, or ejection fraction (EF) <40% were followed for HF hospitalization (primary outcome), all-cause death, and their composite. Myocardial blood flow, left ventricular (LV) mass, volumes, and EF were obtained from PET, and a 'flow/mass ratio' was determined as hyperaemic myocardial blood flow over LV mass indexed to body surface area. A lower flow/mass ratio was independently associated with larger end-diastolic (ß = -0.44, P < 0.001) and end-systolic volume (ß = -0.48, P < 0.001) and lower EF (ß = 0.33, P < 0.001). A flow/mass ratio below the median was associated with an adjusted hazard ratio of 2.47 [95% confidence interval (CI) 1.24-4.93; P = 0.01] for HF hospitalization, 1.95 (95% CI 1.12-3.41; P = 0.02) for death, and 2.20 (95% CI 1.39-3.49; P < 0.001) for the composite. CONCLUSION: An integrated physiological measure of insufficient myocardial perfusion to match global metabolic demand identifies subclinical hypertensive heart disease and elevated risk of HF and death in symptomatic patients with hypertension but without flow-limiting coronary artery disease.

Social Vulnerability and Premature Cardiovascular Mortality Among US Counties, 2014 to 2018.

BACKGROUND: Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain. METHODS: In this cross-sectional study (2014-2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles. RESULTS: Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43-2.36]), ischemic heart disease (1.52 [1.09-2.13]), stroke (2.03 [1.12-3.70]), hypertension (2.71 [1.54-4.75]), and heart failure (3.38 [1.32-8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07-2.54]) and heart failure (2.42 [1.29-4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes. CONCLUSIONS: In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

BACKGROUND: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. METHODS: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). RESULTS: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. CONCLUSIONS: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. These guidelines present an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated and shared decision-making with patients is recommended.

Rationale and pathways forward in the implementation of coronary artery calcium-based enrichment of randomized trials.

The Food and Drug Administration recommends prognostic enrichment of randomized controlled trials (RCTs), aimed at restricting the study population to participants most likely to have events and therefore derive benefit from a given intervention. The coronary artery calcium (CAC) score is powerful discriminator of cardiovascular risk, and in this review we discuss how CAC may be used to augment widely used prognostic enrichment paradigms of RCTs of add-on therapies in primary prevention. We describe recent studies in this space, with special attention to the ability of CAC to further stratify risk among guideline-recommended candidates for add-on risk-reduction therapies. Given the potential benefits in terms of sample size, cost reduction, and overall RCT feasibility of a CAC-based enrichment strategy, we discuss approaches that may help maximize its advantages while minimizing logistical barriers and other challenges. Specifically, use of already existing CAC data to avoid the need to re-scan participants with previously documented high CAC scores, use of increasingly available, large clinical CAC databases to facilitate the identification of potential RCT participants, and implementation of machine learning approaches to measure CAC in existing computed tomography images performed for other purposes, will most likely boost the implementation of a CAC-based enrichment paradigm in future RCTs.

Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review.

The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia, and/or heart failure. The diagnosis of cardiac sarcoidosis (CS) can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes, such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of CS. The mainstay of therapy for CS is immunosuppression; however, no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in CS call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.

Extra-coronary Calcification and Cardiovascular Events: What Do We Know and Where Are We Heading?

PURPOSE OF REVIEW: The coronary artery calcium score is a guideline-endorsed aid for further risk stratification in the primary prevention of atherosclerotic cardiovascular disease. The non-contrast scan performed for detection of coronary artery calcium also gives an opportunity to visualize calcifications in the thoracic aorta and in the heart valves, at no additional cost or radiation exposure. The purpose of this review was to discuss the potential clinical value of measuring thoracic aortic calcification, aortic valve calcification, and mitral annulus calcification. RECENT FINDINGS: After two decades of active research, all three calcifications have been extensively evaluated, across various cohorts. We discuss classic and recent studies, current knowledge gaps, and future directions in this space. The added value of these measurements has traditionally been considered modest at best, and they are not currently discussed in relevant primary prevention guidelines in North America and Europe. However, recent studies evaluating high thoracic calcification thresholds and younger populations have further enriched this space. Specifically, some studies suggest that detection of severe thoracic aortic calcification may be helpful in further risk assessment and that detection of aortic valve calcifications may have important prognostic implications in younger individuals. Although more research is needed, particularly in larger young-to-middle-aged cohorts, future guidelines might consider including these features as risk-enhancing factors.

Multimodality imaging to distinguish between benign and malignant cardiac masses.

BACKGROUND: To compare the diagnostic accuracy of CMR and FDG-PET/CT and their complementary role to distinguish benign vs malignant cardiac masses. METHODS: Retrospectively assessed patients with cardiac mass who underwent CMR and FDG-PET/CT within a month between 2003 and 2018. RESULTS: 72 patients who had CMR and FDG-PET/CT were included. 25 patients (35%) were diagnosed with benign and 47 (65%) were diagnosed with malignant masses. 56 patients had histological correlation: 9 benign and 47 malignant masses. CMR and FDG-PET/CT had a high accuracy in differentiating benign vs malignant masses, with the presence of CMR features demonstrating a higher sensitivity (98%), while FDG uptake with SUVmax/blood pool ≥ 3.0 demonstrating a high specificity (88%). Combining multiple (> 4) CMR features and FDG uptake (SUVmax/blood pool ratio ≥ 3.0) yielded a sensitivity of 85% and specificity of 88% to diagnose malignant masses. Over a mean follow-up of 2.6 years (IQR 0.3-3.8 years), risk-adjusted mortality were highest among patients with an infiltrative border on CMR (adjusted HR 3.1; 95% CI 1.5-6.5; P = .002) or focal extracardiac FDG uptake (adjusted HR 3.8; 95% CI 1.9-7.7; P < .001). CONCLUSION: Although CMR and FDG-PET/CT can independently diagnose benign and malignant masses, the combination of these modalities provides complementary value in select cases.