Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.

BACKGROUND: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.

Pathophysiology of Preeclampsia-Induced Vascular Dysfunction and Implications for Subclinical Myocardial Damage and Heart Failure.

Tragically, preeclampsia is a leading cause of pregnancy-related complications and is linked to a heightened risk for morbid and fatal cardiovascular disease (CVD) outcomes. Although the mechanism connecting preeclampsia to CVD risk has yet to be fully elucidated, evidence suggests distinct pathways of early and late preeclampsia with shared CV risk factors but with profound differences in perinatal and postpartum risk to the mother and infant. In early preeclampsia, <34 weeks of gestation, systemic vascular dysfunction contributes to near-term subclinical myocardial damage. Hypertrophy and diastolic abnormalities persist postpartum and contribute to early onset heart failure (HF). This HF risk remains elevated decades later and contributes to premature death. Black women are at the highest risk of preeclampsia and HF. These findings support closer monitoring of women postpartum, especially for those with early and severe preeclampsia to control chronic hypertension and reduce the potentially preventable sequelae of heightened CVD and HF risk.

Evaluating the American Heart Association/American College of Cardiology Guideline-Recommended and Contemporary Pretest Probability Models in a Mixed Asian Cohort: The Contribution of Coronary Artery Calcium.

BACKGROUND: Most pretest probability (PTP) tools for obstructive coronary artery disease (CAD) were Western -developed. The most appropriate PTP models and the contribution of coronary artery calcium score (CACS) in Asian populations remain unknown. In a mixed Asian cohort, we compare 5 PTP models: local assessment of the heart (LAH), CAD Consortium (CAD2), risk factor-weighted clinical likelihood, the American Heart Association/American College of Cardiology and the European Society of Cardiology PTP and 3 extended versions of these models that incorporated CACS: LAH(CACS), CAD2(CACS), and the CACS-clinical likelihood. METHODS AND RESULTS: The study cohort included 771 patients referred for stable chest pain. Obstructive CAD prevalence was 27.5%. Calibration, area under the receiver-operating characteristic curves (AUC) and net reclassification index were evaluated. LAH clinical had the best calibration (χ2 5.8; P=0.12). For CACS models, LAH(CACS) showed least deviation between observed and expected cases (χ2 37.5; P<0.001). There was no difference in AUCs between the LAH clinical (AUC, 0.73 [95% CI, 0.69-0.77]), CAD2 clinical (AUC, 0.72 [95% CI, 0.68-0.76]), risk factor-weighted clinical likelihood (AUC, 0.73 [95% CI: 0.69-0.76) and European Society of Cardiology PTP (AUC, 0.71 [95% CI, 0.67-0.75]). CACS improved discrimination and reclassification of the LAH(CACS) (AUC, 0.88; net reclassification index, 0.46), CAD2(CACS) (AUC, 0.87; net reclassification index, 0.29) and CACS-CL (AUC, 0.87; net reclassification index, 0.25). CONCLUSIONS: In a mixed Asian cohort, Asian-derived LAH models had similar discriminatory performance but better calibration and risk categorization for clinically relevant PTP cutoffs. Incorporating CACS improved discrimination and reclassification. These results support the use of population-matched, CACS-inclusive PTP tools for the prediction of obstructive CAD.

Cardiovascular testing recovery in Latin America one year into the COVID-19 pandemic: An analysis of data from an international longitudinal survey.

Background: The COVID-19 pandemic disproportionately impacted Latin America (LATAM), significantly disrupting cardiovascular testing. This study evaluated cardiac procedure recovery in LATAM one year after the outbreak. Methods: The International Atomic Energy Agency (IAEA) surveyed 669 centers in 107 countries worldwide, including 135 facilities in 19 LATAM countries, to assess cardiovascular procedure volumes in March 2019, April 2020, and April 2021, and changes in center practices and staffing conditions one year into the COVID-19 pandemic. Findings: LATAM centers reported a 21 % decrease in procedure volumes in April 2021 from pre-pandemic-baseline, vs. a 0 % change in the rest of the world (RoW), and greater volume reductions for almost all procedure types. Centers in Central America and Mexico reported the largest procedure reductions (47 % reduction) compared to the Caribbean (15 %), and South America (14 %, p = 0.01), and this LATAM region was a significant predictor of lower procedure recovery in multivariable regression. More LATAM centers reported reduced salaries and increased layoffs of clinical staff compared to RoW, and LATAM respondents estimated that half of physician and non-physician staff experienced excess psychological stress related to the pandemic, compared to 25 % and 30 % in RoW (p < 0.001). Conclusions: Cardiovascular testing recovery in LATAM trailed behind RoW for most procedure types, with centers in Central America and Mexico reporting the greatest volume reductions. This study found lasting impacts of COVID-19 on cardiovascular care in LATAM and the need for mental health support for LATAM healthcare workers in current and future pandemics.

Comparison of risk profiles of participants in the Women's IschemiA TRial to Reduce events In non-ObstRuctive CAD (WARRIOR) trial, using Coronary Computed Tomography Angiography vs Invasive Coronary Angiography.

OBJECTIVE: To compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). METHODS: The WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. RESULTS: An initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. CONCLUSIONS: Among this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000.

BACKGROUND: Although a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. OBJECTIVES: Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. METHODS: The authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years). RESULTS: The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]). CONCLUSIONS: Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.

Prediction of the development of new coronary atherosclerotic plaques with radiomics.

BACKGROUND: Radiomics is expected to identify imaging features beyond the human eye. We investigated whether radiomics can identify coronary segments that will develop new atherosclerotic plaques on coronary computed tomography angiography (CCTA). METHODS: From a prospective multinational registry of patients with serial CCTA studies at ≥ 2-year intervals, segments without identifiable coronary plaque at baseline were selected and radiomic features were extracted. Cox models using clinical risk factors (Model 1), radiomic features (Model 2) and both clinical risk factors and radiomic features (Model 3) were constructed to predict the development of a coronary plaque, defined as total PV â€‹≥ â€‹1 â€‹mm3, at follow-up CCTA in each segment. RESULTS: In total, 9583 normal coronary segments were identified from 1162 patients (60.3 â€‹± â€‹9.2 years, 55.7% male) and divided 8:2 into training and test sets. At follow-up CCTA, 9.8% of the segments developed new coronary plaque. The predictive power of Models 1 and 2 was not different in both the training and test sets (C-index [95% confidence interval (CI)] of Model 1 vs. Model 2: 0.701 [0.690-0.712] vs. 0.699 [0.0.688-0.710] and 0.696 [0.671-0.725] vs. 0.0.691 [0.667-0.715], respectively, all p â€‹> â€‹0.05). The addition of radiomic features to clinical risk factors improved the predictive power of the Cox model in both the training and test sets (C-index [95% CI] of Model 3: 0.772 [0.762-0.781] and 0.767 [0.751-0.787], respectively, all p â€‹< â€‹00.0001 compared to Models 1 and 2). CONCLUSION: Radiomic features can improve the identification of segments that would develop new coronary atherosclerotic plaque. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT0280341.

Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial.

BACKGROUND: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. METHODS AND RESULTS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive-assigned women revascularized versus 81.2% of invasive-assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive-assigned women and 74.8% of invasive-assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4-year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline-directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77-1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76-1.14]; P=0.49), with no significant sex-by-treatment-group interactions. CONCLUSIONS: Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial. REGISTRATION: URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

Fetal Arrhythmia Leading to a Diagnosis of Congenital Long QT Syndrome Type II.

We describe the case of an asymptomatic young pregnant woman with a diagnosis of congenital long QT syndrome type II in the context of in utero fetal 2:1 heart block and ventricular tachycardia. The presentation, clinical considerations, and management of the mother and baby in the antepartum and postpartum periods are discussed.

Recovery Rates of Diagnostic Cardiac Procedural Volume in Oceania 1 Year Into COVID-19: The IAEA Non-Invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID 2).

AIM: The aim of this study was to assess the recovery rates of diagnostic cardiac procedure volumes in the Oceania Region, midway through the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A survey was performed comparing procedure volumes between March 2019 (pre-pandemic), April 2020 (during first wave of COVID-19 pandemic), and April 2021 (1 year into the COVID-19 pandemic). A total of 31 health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, as well as teaching and non-teaching hospitals. A comparison was made with 549 centres in 96 countries in the rest of the world (RoW) outside of Oceania. The total number and median percentage change in procedure volume were measured between the three timepoints, compared by test type and by facility. RESULTS: A total of 11,902 cardiac diagnostic procedures were performed in Oceania in April 2021 as compared with 11,835 pre-pandemic in March 2019 and 5,986 in April 2020; whereas, in the RoW, 499,079 procedures were performed in April 2021 compared with 497,615 pre-pandemic in March 2019 and 179,014 in April 2020. There was no significant difference in the median recovery rates for total procedure volumes between Oceania (-6%) and the RoW (-3%) (p=0.81). While there was no statistically significant difference in percentage recovery been functional ischaemia testing and anatomical coronary testing in Oceania as compared with the RoW, there was, however, a suggestion of poorer recovery in anatomical coronary testing in Oceania as compared with the RoW (CT coronary angiography -16% in Oceania vs -1% in RoW, and invasive coronary angiography -20% in Oceania vs -9% in RoW). There was no statistically significant difference in recovery rates in procedure volume between metropolitan vs regional (p=0.44), public vs private (p=0.92), hospital vs outpatient (p=0.79), or teaching vs non-teaching centres (p=0.73). CONCLUSIONS: Total cardiology procedure volumes in Oceania normalised 1 year post-pandemic compared to pre-pandemic levels, with no significant difference compared with the RoW and between the different types of health care facilities.

Disparities in Noninvasive Traditional and Advanced Testing for Coronary Artery Disease: Findings from the INCAPS-COVID 2 Study.

The COVID-19 pandemic disrupted the delivery of cardiovascular care, including noninvasive testing protocols and test selection for the evaluation of coronary artery disease (CAD). Trends in test selection in traditional versus advanced noninvasive tests for CAD during the pandemic and in countries of varying income status have not been well studied. The International Atomic Energy Agency conducted a global survey to assess the pandemic-related changes in the practice of cardiovascular diagnostic testing. Site procedural volumes for noninvasive tests to evaluate CAD from March 2019 (prepandemic), April 2020 (onset), and April 2021 (initial recovery) were collected. We considered traditional testing modalities, such as exercise electrocardiography, stress echocardiography, and stress single-photon emission computed tomography, and advanced testing modalities, such as stress cardiac magnetic resonance, coronary computed tomography angiography, and stress positron emission tomography. Survey data were obtained from 669 centers in 107 countries, reporting the performance of 367,933 studies for CAD during the study period. Compared with 2019, traditional tests were performed 14% less frequently (recovery rate 82%) in 2021 versus advanced tests, which were performed 15% more frequently (128% recovery rate). Coronary computed tomography angiography, stress cardiac magnetic resonance, and stress positron emission tomography showed 14%, 25%, and 25% increases in volumes from 2019 to 2021, respectively. The increase in advanced testing was isolated to high- and upper middle-income countries, with 132% recovery in advanced tests by 2021 compared with 55% in lower income nations. The COVID-19 pandemic exacerbated economic disparities in CAD testing practice between wealthy and poorer countries. Greater recovery rates and even new growth were observed for advanced imaging modalities; however, this growth was restricted to wealthy countries. Efforts to reduce practice variations in CAD testing because of economic status are warranted.

Cardiovascular multimodality imaging in women: a scientific statement of the European Association of Cardiovascular Imaging of the European Society of Cardiology.

Cardiovascular diseases (CVD) represent an important cause of mortality and morbidity in women. It is now recognized that there are sex differences regarding the prevalence and the clinical significance of the traditional cardiovascular (CV) risk factors as well as the pathology underlying a range of CVDs. Unfortunately, women have been under-represented in most CVD imaging studies and trials regarding diagnosis, prognosis, and therapeutics. There is therefore a clear need for further investigation of how CVD affects women along their life span. Multimodality CV imaging plays a key role in the diagnosis of CVD in women as well as in prognosis, decision-making, and monitoring of therapeutics and interventions. However, multimodality imaging in women requires specific consideration given the differences in CVD between the sexes. These differences relate to physiological changes that only women experience (e.g. pregnancy and menopause) as well as variation in the underlying pathophysiology of CVD and also differences in the prevalence of certain conditions such as connective tissue disorders, Takotsubo, and spontaneous coronary artery dissection, which are all more common in women. This scientific statement on CV multimodality in women, an initiative of the European Association of Cardiovascular Imaging of the European Society of Cardiology, reviews the role of multimodality CV imaging in the diagnosis, management, and risk stratification of CVD, as well as highlights important gaps in our knowledge that require further investigation.

Changes in use of preventive medications after assessment of chest pain by coronary computed tomography angiography: A meta-analysis.

BACKGROUND: Coronary computed tomography angiogram (CCTA) is a crucial tool for diagnosing CAD, but its impact on altering preventive medications is not well-documented. This systematic review aimed to compare changes in aspirin and statin therapy following CCTA and functional stress testing in patients with suspected CAD, and in those underwent CCTA when stratified by the presence/absence of plaque. RESULTS: Eight studies involving 42,812 CCTA patients and 64,118 cardiac stress testing patients were analyzed. Compared to functional testing, CCTA led to 66 â€‹% more changes in statin therapy (pooled RR, 95 â€‹% CI [1.28-2.15]) and a 74 â€‹% increase in aspirin prescriptions (pooled RR, 95 â€‹% CI [1.34-2.26]). For medication modifications based on CCTA results, 13 studies (47,112 patients with statin data) and 11 studies (12,089 patients with aspirin data) were included. Patients with any plaque on CCTA were five times more likely to use or intensify statins compared to those without CAD (pooled RR, 5.40, 95 â€‹% CI [4.16-7.00]). Significant heterogeneity remained, which decreased when stratified by diabetes rates. Aspirin use increased eightfold after plaque detection (pooled RR, 8.94 [95 â€‹% CI, 4.21-19.01]), especially with obstructive plaque findings (pooled RR, 9.41, 95 â€‹% CI [2.80-39.02]). CONCLUSION: In conclusion, CCTA resulted in higher changes in statin and aspirin therapy compared to cardiac stress testing. Detection of plaque by CCTA significantly increased statin and aspirin therapy.

Prevalence and Prognostic Importance of Abnormal Positron Emission Tomography Among Asymptomatic Patients With Diabetes Mellitus.

BACKGROUND: Ischemia and reduced global myocardial blood flow reserve (MBFR) are associated with high cardiovascular risk among symptomatic patients with diabetes mellitus (DM). OBJECTIVES: This study aimed to assess the prevalence and prognostic importance of silent ischemia and reduced MBFR among asymptomatic patients with DM. METHODS: This study included 2,730 consecutive patients with DM, without known coronary artery disease (CAD) or cardiomyopathy, who underwent rubidium-82 rest/stress positron emission tomography (PET) myocardial perfusion imaging (MPI) from 2010 to 2016. These patients were followed up for all-cause mortality (n = 461) for a median follow-up of 3 years. Patients were considered asymptomatic if neither chest pain nor dyspnea was elicited. Rates of ischemia, reduced MBFR, and coronary microvascular dysfunction on PET were assessed in both groups. Cox regression was used to define the independent association of abnormal MPI markers with mortality. RESULTS: One-quarter of patients with DM (23.7%; n = 647) were asymptomatic; ischemia was present in 30.5% (n = 197), reduced MBFR in 62.3% (n = 361), and coronary microvascular dysfunction in 32.7% (n = 200). In adjusted analyses, reduced MBFR (HR per 0.1 unit decrease in MBFR: 1.08 [95% CI: 1.03-1.12]; P = 0.001) and reduced ejection fraction (HR per 5% decrease: 1.10 [95% CI: 1.01-1.18]; P = 0.02) were independently prognostic of mortality among asymptomatic patients, but ischemia was not. This was comparable to DM patients with symptoms. Insulin use and older age were significant predictors of reduced MBFR among asymptomatic patients with DM. CONCLUSIONS: In both symptomatic and asymptomatic patients with DM, impairment in MBFR is common and associated with greater mortality risk.