Multiparametric Cardiac Magnetic Resonance Imaging to Discriminate Endomyocardial Biopsy-Proven Chronic Myocarditis From Healed Myocarditis.

BACKGROUND: Detecting ongoing inflammation in myocarditis patients has prognostic relevance, but there are limited data on the detection of chronic myocarditis and its differentiation from healed myocarditis. OBJECTIVES: This study sought to assess the performance of cardiac magnetic resonance (CMR) for the detection of ongoing inflammation and the discrimination of chronic myocarditis from healed myocarditis. METHODS: Consecutive patients with persistent symptoms (>30 days) suggestive of myocarditis were prospectively enrolled from a single tertiary center. All patients underwent a multiparametric 1.5-T CMR protocol including biventricular strain, T1/T2 mapping, and late gadolinium enhancement (LGE). Endomyocardial biopsy was chosen for the reference standard diagnosis. RESULTS: Among 452 consecutive patients, 103 (median age: 50 years; 66 men) had evaluable CMR and cardiopathologic reference diagnosis: 53 (51%) with chronic lymphocytic myocarditis and 50 (49%) with healed myocarditis. T2 mapping as a single parameter showed the best accuracy in detecting chronic myocarditis, if abnormal in ≥3 segments (92%; 95% CI: 85-97), and provided the best discrimination from healed myocarditis, as defined by the area under the receiver-operating characteristic curve (0.87 [95% CI: 0.79-0.93]; P < 0.001), followed by radial peak systolic strain rate of the left ventricle (0.86) and the right ventricle (0.84); T1 mapping (0.64), extracellular volume fraction (0.62), and LGE (0.57). Specificity increased when T2 mapping was combined with elevation of either troponin or C-reactive protein. CONCLUSIONS: A multiparametric CMR protocol allows detection of ongoing myocardial inflammation and discrimination of chronic myocarditis from healed myocarditis, with segmental T2 mapping and biventricular strain analysis showing higher diagnostic accuracy compared with T1 mapping, extracellular volume fraction, and LGE. The use of biomarkers (troponin or C-reactive protein) may improve specificity.

Relationship between epicardial adipose tissue and coronary atherosclerosis by CCTA in young adults (18-45).

Objective: Epicardial adipose tissue (EAT) is implicated in the pathogenesis and progression of coronary artery disease (CAD). Limited data exists on the interplay between EAT and atherosclerosis in young individuals. Our study aims to explore the relationship between EAT and CAD in a young cohort. Methods: All young (18-45 years) patients without prior CAD, referred for coronary computed tomography angiography (CCTA) from 2016 to 2022 were included. EAT volume and coronary artery calcium (CAC) were calculated from dedicated non-contrast scans. Coronary plaque presence, extent, and volume were quantified from CCTA. Multivariable logistic regression models for the presence of CAD, defined as any coronary atherosclerosis, were performed. Results: Overall, 712 patients (39±4.8 years, 54 % female) with 45 % Hispanic, and 21 % non-Hispanic Black were included. Patients with CAD had higher EAT volume than those without (80.80 mL ± 36.00 vs 55.16 mL ± 27.92; P < 0.001). In those with CAC=0, higher EAT was associated with the presence of CAD compared to lower EAT volume (P < 0.001). An EAT volume >76 mL was associated with higher CAC (P < 0.001), segment involvement score (P < 0.001), and quantitative total, non-calcified, and low-attenuation plaque volumes (P < 0.002). At multivariable analysis, EAT volume (per 10 mL, OR: 1.21; 95 %CI: 1.12-1.30; P < 0.0001) was independently associated with the presence of CAD. Conclusion: In a diverse cohort of young adults without history of CAD and undergoing a clinically indicated CCTA, EAT volume was independently associated with the presence of CAD. Our findings highlight EAT potential as a novel marker for CAD risk-assessment and a potential therapeutic target in young patients.

Relationship of Subendocardial Perfusion to Myocardial Injury, Cardiac Structure, and Clinical Outcomes Among Patients With Hypertension.

BACKGROUND: Coronary microvascular dysfunction has been implicated in the development of hypertensive heart disease and heart failure, with subendocardial ischemia identified as a driver of sustained myocardial injury and fibrosis. We aimed to evaluate the relationships of subendocardial perfusion with cardiac injury, structure, and a composite of major adverse cardiovascular and cerebral events consisting of death, heart failure hospitalization, myocardial infarction, and stroke. METHODS: Layer-specific blood flow and myocardial flow reserve (MFR; stress/rest myocardial blood flow) were assessed by 13N-ammonia perfusion positron emission tomography in consecutive patients with hypertension without flow-limiting coronary artery disease (summed stress score <3) imaged at Brigham and Women's Hospital (Boston, MA) from 2015 to 2021. In this post hoc observational study, biomarkers, echocardiographic parameters, and longitudinal clinical outcomes were compared by tertiles of subendocardial MFR (MFRsubendo). RESULTS: Among 358 patients, the mean age was 70.6±12.0 years, and 53.4% were male. The median MFRsubendo was 2.57 (interquartile range, 2.08-3.10), and lower MFRsubendo was associated with older age, diabetes, lower renal function, greater coronary calcium burden, and higher systolic blood pressure (P<0.05 for all). In cross-sectional multivariable regression analyses, the lowest tertile of MFRsubendo was associated with myocardial injury and with greater left ventricular wall thickness and volumes compared with the highest tertile. Relative to the highest tertile, low MFRsubendo was independently associated with an increased rate of major adverse cardiovascular and cerebral events (adjusted hazard ratio, 2.99 [95% CI, 1.39-6.44]; P=0.005) and heart failure hospitalization (adjusted hazard ratio, 2.76 [95% CI, 1.04-7.32; P=0.042) over 1.1 (interquartile range, 0.6-2.8) years median follow-up. CONCLUSIONS: Among patients with hypertension without flow-limiting coronary artery disease, impaired MFRsubendo was associated with cardiovascular risk factors, elevated cardiac biomarkers, cardiac structure, and clinical events.

Lipoprotein(a) and Coronary Plaque in Asymptomatic Individuals: The Miami Heart Study at Baptist Health South Florida.

BACKGROUND: Elevated levels of lipoprotein(a) (Lp(a)) are independently associated with an increased risk of atherosclerotic cardiovascular disease events. However, the mechanisms driving this association are poorly understood. We aimed to evaluate the association between Lp(a) and coronary plaque characteristics in a contemporary US cohort without clinical atherosclerotic cardiovascular disease, undergoing coronary computed tomography angiography, the noninvasive gold standard for the assessment of coronary atherosclerosis. METHODS: We used baseline data from the Miami Heart Study-a community-based, prospective cohort study-which included asymptomatic adults aged 40 to 65 years evaluated using coronary computed tomography angiography. Those taking any lipid-lowering therapies were excluded. Elevated Lp(a) was defined as ≥125 nmol/L. Outcomes included any plaque, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. RESULTS: Among 1795 participants (median age, 52 years; 54.3% women; 49.6% Hispanic), 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, individuals with Lp(a) ≥125 nmol/L had a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, although differences were only statistically significant for the presence of any coronary plaque and ≥2 high-risk features. In multivariable models, elevated Lp(a) was independently associated with the presence of any coronary plaque (odds ratio, 1.40, [95% CI, 1.05-1.86]) and with ≥2 high-risk features (odds ratio, 3.94, [95% CI, 1.82-8.52]), although only 35 participants had this finding. Among participants with a coronary artery calcium score of 0 (n=1200), those with Lp(a) ≥125 nmol/L had a significantly higher percentage of any plaque compared with those with Lp(a) <125 nmol/L (24.2% versus 14.2%; P<0.001). CONCLUSIONS: In this contemporary analysis, elevated Lp(a) was independently associated with the presence of coronary plaque. Larger studies are needed to confirm the strong association observed with the presence of multiple high-risk coronary plaque features.

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry.

BACKGROUND: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. OBJECTIVE: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. METHODS: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). RESULTS: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001). CONCLUSIONS: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Septal late enhancement by cardiac CT is associated with repeat ablation in nonischemic cardiomyopathy patients.

INTRODUCTION: Scar substrate in nonischemic cardiomyopathy (NICM) patients is often difficult to identify. Advances in cardiac imaging, especially using late iodine-enhanced computed tomography (LIE-CT), allow better characterization of scars giving rise to ventricular tachycardia (VT). Currently, there are limited data on clinical correlates of CT-derived scar substrates in NICM. We sought assess the relationship between scar location on LIE-CT and outcomes after radiofrequency catheter ablation (RFCA) in NICM patients with VT. METHODS: From 2020 to 2022, consecutive patients with NICM undergoing VT RFCA with integration of cardiac CT scar modeling (inHeart, Pessac, France) were included at two US tertiary care centers. The CT protocol included both arterial-enhanced imaging for anatomical modeling and LIE-CT for scar assessment. The distribution of substrate on CT was analyzed in relation to patient outcomes, with primary endpoints being VT recurrence and the need for repeat ablation procedure. RESULTS: Sixty patients were included (age 64 ± 12 years, 90% men). Over a median follow-up of 120 days (interquartile range [IQR]: 41-365), repeat ablation procedures were required in 32 (53%). VT recurrence occurred in 46 (77%), with a median time to recurrence of 40 days (IQR: 8-65). CT-derived total scar volume positively correlated with intrinsic QRS duration (r = .34, p = 0.008). Septal scar was found on CT in 34 (57%), and lateral scar in 40 (7%). On univariate logistic regression, septal scar was associated with increased odds of repeat ablation (odds ratio [OR]: 2.9 [1.0-8.4]; p = 0.046), while lateral scar was not (OR: 0.9 [0.3-2.7]; p = 0.855). Septal scar better predicted VT recurrence when compared to lateral scar, but neither were statistically significant (septal scar OR: 3.0 [0.9-10.7]; p = 0.078; lateral scar OR: 1.7 [0.5-5.9]; p = 0.391). CONCLUSION: In this tertiary care referral population, patients with NICM undergoing VT catheter ablation with septal LIE-CT have nearly threefold increased risk of need for repeat ablation.

Comparative effectiveness of positron emission tomography and single-photon emission computed tomography myocardial perfusion imaging for predicting risk in patients with cardiometabolic disease.

BACKGROUND: The epidemiology of coronary artery disease (CAD) has shifted, with increasing prevalence of cardiometabolic disease and decreasing findings of obstructive CAD on myocardial perfusion imaging (MPI). Coronary microvascular dysfunction (CMD), defined as impaired myocardial flow reserve (MFR) by positron emission tomography (PET), has emerged as a key mediator of risk. We aimed to assess whether PET MFR provides additive value for risk stratification of cardiometabolic disease patients compared with single-photon emission computed tomography (SPECT) MPI. METHODS: We retrospectively followed patients referred for PET, exercise SPECT, or pharmacologic SPECT MPI with cardiometabolic disease (obesity, diabetes, or chronic kidney disease) and without known CAD. We compared rates and hazards of composite major adverse cardiovascular events (MACEs) (annualized cardiac mortality or acute myocardial infarction) among propensity-matched PET and SPECT patients using Poisson and Cox regression. Normal SPECT was defined as a total perfusion deficit (TPD) of <5%, reflecting the absence of obstructive CAD. Normal PET was defined as a TPD of <5% plus an MFR of ≥2.0. RESULTS: Among 21,544 patients referred from 2006 to 2020, cardiometabolic disease was highly prevalent (PET: 2308 [67%], SPECT: 9984 [55%]) and higher among patients referred to PET (P < 0.001). Obstructive CAD findings (TPD > 5%) were uncommon (PET: 21% and SPECT: 11%). Conversely, impaired MFR on PET (<2.0) was common (62%). In a propensity-matched analysis over a median 6.4-year follow-up, normal PET identified low-risk (0.9%/year MACE) patients, and abnormal PET identified high-risk (4.2%/year MACE) patients with cardiometabolic disease; conversely, those with normal pharmacologic SPECT remained moderate-risk (1.6%/year, P < 0.001 compared to normal PET). CONCLUSIONS: Cardiometabolic disease is common among patients referred for MPI and is associated with a heterogenous level of risk. Compared with pharmacologic SPECT, PET with MFR can detect nonobstructive CAD including CMD and can more accurately discriminate low-risk from higher-risk individuals.

Lipoprotein(a), Oxidized Phospholipids, and Progression to Symptomatic Heart Failure: The CASABLANCA Study.

BACKGROUND: Higher lipoprotein(a) and oxidized phospholipid concentrations are associated with increased risk for coronary artery disease and valvular heart disease. The role of lipoprotein(a) or oxidized phospholipid as a risk factor for incident heart failure (HF) or its complications remains uncertain. METHODS AND RESULTS: A total of 1251 individuals referred for coronary angiography in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study were stratified on the basis of universal definition of HF stage; those in stage A/B (N=714) were followed up for an average 3.7 years for incident stage C/D HF or the composite of HF/cardiovascular death. During follow-up, 105 (14.7%) study participants in stage A/B progressed to symptomatic HF and 57 (8.0%) had cardiovascular death. In models adjusted for multiple HF risk factors, including severe coronary artery disease and aortic stenosis, individuals with lipoprotein(a) ≥150 nmol/L were at higher risk for progression to symptomatic HF (hazard ratio [HR], 1.90 [95% CI, 1.15-3.13]; P=0.01) or the composite of HF/cardiovascular death (HR, 1.71 [95% CI, 1.10-2.67]; P=0.02). These results remained significant after further adjustment of the model to include prior myocardial infarction (HF: HR, 1.89, P=0.01; HF/cardiovascular death: HR, 1.68, P=0.02). Elevated oxidized phospholipid concentrations were similarly associated with risk, particularly when added to higher lipoprotein(a). In Kaplan-Meier analyses, individuals with stage A/B HF and elevated lipoprotein(a) had shorter time to progression to stage C/D HF or HF/cardiovascular death (both log-rank P<0.001). CONCLUSIONS: Among individuals with stage A or B HF, higher lipoprotein(a) and oxidized phospholipid concentrations are independent risk factors for progression to symptomatic HF or cardiovascular death. REGISTRATION: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT00842868.

Sex Differences in Coronary Artery Disease Characteristics Among Patients With Type 2 Myocardial Infarction.

Background: Type 2 myocardial infarction (MI) results from coronary supply and demand imbalance and has a poor prognosis. It is crucial to identify potential sex-based differences in the prevalence and nature of coronary artery disease (CAD) within this population. Objectives: The purpose of this study was to evaluate sex-based disease differences in type 2 MI among patients evaluated with coronary computed tomography angiography and fractional flow reserve. Methods: In a single-center, prospective study, patients with strictly adjudicated type 2 MI underwent coronary computed tomography angiography with fractional flow reserve. Results: Among 50 study participants enrolled, 50% were women. A similar mix of MI precipitants was present in both sexes. ST-segment depression was more common in women (64% vs 32%), while men were more likely to have T wave inversion (68% vs 36%). Women and men had comparable coronary artery calcium scores (median: 152 [Q1, Q3: 45, 762] vs 234 [Q1, Q3: 56, 422]). Prevalence of any CAD (84% vs 100%), obstructive CAD (24% vs 28%), and hemodynamically significant focal stenosis (20% vs 32%) were similar between sexes. Total plaque volume was similar between sexes, but women had significantly lower levels of low-attenuation plaque (median: 3 [Q1, Q3: 1, 7] vs 9 [Q1, Q3: 3, 14]). Conclusions: Among patients with type 2 MI, prevalence of any CAD and obstructive CAD did not differ according to sex. Total plaque volume was similar between sexes, but women had a lower volume of low-attenuation plaque (DEFINing the PrEvalence and Characteristics of Coronary Artery Disease Among Patients With TYPE 2 Myocardial Infarction Using CT-FFR [DEFINE TYPE2MI]; NCT04864119).

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.

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.

Effects of Age and Sex on Systemic Inflammation and Cardiometabolic Function in Individuals with Type 2 Diabetes.

Objective: Systemic inflammation, aging, and type 2 diabetes (T2DM) all contribute to the development of cardiovascular dysfunction and impaired aerobic exercise capacity but their interplay remains unclear. This study evaluates the impact of age, sex, and inflammation on coronary and peripheral vascular function and exercise capacity in elderly individuals with and without type 2 diabetes (T2DM). Research Design and Methods: Elderly individuals (age ≥65 years) underwent biochemical and tissue inflammatory phenotyping, cardiopulmonary exercise testing (CPET), cardiovascular magnetic resonance (CMR) imaging, and vascular reactivity testing. Correlation and regression analyses determined the effects of systemic inflammation, older age, and sex on cardiovascular health, stratified by T2DM status. Results: For the 133 recruited individuals (44% female; median age 71, IQR=7 years, 41% with T2DM) the presence of T2DM did not have an effect on most blood serum inflammatory markers and skin biopsies. Hyperemic myocardial blood flow (hMBF), flow-mediated, and flow-independent nitroglycerin induced brachial artery dilation were significantly impaired in males, but not females with T2DM. Peak VO2 was lower with T2DM (p=0.022), mostly because of the effect of T2DM in females. Females showed more adverse myocardial remodeling assessed by extracellular volume (p=0.008), independent of T2DM status. Conclusions: Our findings suggest that the pathophysiological manifestations of T2DM on vascular function and aerobic exercise capacity are distinct in elderly males and females and this may reflect underlying differences in vascular and myocardial aging in the presence of T2DM.

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.

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.

Interaction between risk factors, coronary calcium, and CCTA plaque characteristics in patients aged 18-45 years.

AIMS: The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. METHODS AND RESULTS: We included 907 symptomatic young patients (18-45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors {RFs, odds ratio [OR] 7.13 (2.14-23.7) and OR 10.26 (3.36-31.2), respectively}. Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years [OR 3.62 (2.05-6.41)] and family history of premature coronary artery disease (FHx) [OR 2.76 (1.67-4.58)]. Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified plaque (NCP, 37.2%) and low-attenuation plaque (LAP, 4.24%) burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively NCP was FHx [OR 2.29 (1.08-4.86)]. CONCLUSION: In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC >0, but there was a significant burden of NCP and LAP even within the non-obstructive group.

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.

Assessment of atherosclerotic plaque burden: comparison of AI-QCT versus SIS, CAC, visual and CAD-RADS stenosis categories.

This study assesses the agreement of Artificial Intelligence-Quantitative Computed Tomography (AI-QCT) with qualitative approaches to atherosclerotic disease burden codified in the multisociety 2022 CAD-RADS 2.0 Expert Consensus. 105 patients who underwent cardiac computed tomography angiography (CCTA) for chest pain were evaluated by a blinded core laboratory through FDA-cleared software (Cleerly, Denver, CO) that performs AI-QCT through artificial intelligence, analyzing factors such as % stenosis, plaque volume, and plaque composition. AI-QCT plaque volume was then staged by recently validated prognostic thresholds, and compared with CAD-RADS 2.0 clinical methods of plaque evaluation (segment involvement score (SIS), coronary artery calcium score (CACS), visual assessment, and CAD-RADS percent (%) stenosis) by expert consensus blinded to the AI-QCT core lab reads. Average age of subjects were 59 ± 11 years; 44% women, with 50% of patients at CAD-RADS 1-2 and 21% at CAD-RADS 3 and above by expert consensus. AI-QCT quantitative plaque burden staging had excellent agreement of 93% (k = 0.87 95% CI: 0.79-0.96) with SIS. There was moderate agreement between AI-QCT quantitative plaque volume and categories of visual assessment (64.4%; k = 0.488 [0.38-0.60]), and CACS (66.3%; k = 0.488 [0.36-0.61]). Agreement between AI-QCT plaque volume stage and CAD-RADS % stenosis category was also moderate. There was discordance at small plaque volumes. With ongoing validation, these results demonstrate a potential for AI-QCT as a rapid, reproducible approach to quantify total plaque burden.