Harmonizing multimodality imaging results using Bayesian analysis: the case of CT coronary angiography and CT-derived fractional flow reserve.

Coronary computed tomographic angiography (CCTA) may provide both anatomic and CT fractional flow reserve data (CTFFR). The objective is to use Bayesian analysis to develop a model wherein the probability of significant coronary artery disease (CAD) by CTFFR can be determined given the prior probability (P) of the combined clinical and CCTA result. 172 patients referred for CCTA and subsequently underwent coronary angiography were automatically referred to CTFFR analysis. A clinical P risk score (CRS) was calculated per patient. CCTA exams were scored using CAD-RADS classification. CTFFR results were generated. CAD was defined as ≥ 3 RAD class for CCTA and ≤ .80 by CTFFR. P was calculated using CCTA and CTFFR accuracy from a prior clinical trial: post-test P for the CCTA result used the CRS as the prior risk, and CTFFR P used the post-test CRS + CCTA P as the prior risk (tri-variable). Patients were classified for each model into low (< 5%), intermediate, (5-70%) and high (> 70%) risk groups. There were 100 patients (58%), who had significant CAD at angiography. 58 patients had discordant CCTA/CTFFR results. The inclusion of the CRS and CRS + CCTA in the prior progressively reduced the intermediate risk cohort from 83 to 41% (p < 0.0001). Correct classifications (low-risk, negative angiogram plus high-risk, positive angiogram) increased by model: CRS = 12%, CRS + CCTA = 25%, CRS + CTFFR = 33%, CRS + CCTA + CTFFR = 44% (p < 0.001). Incorrect classifications were reduced to 15%. The tri-variable model performed better than either CCTA or CTFFR alone for all patients and for the sub-group with discordant imaging results. Discrepant CCTA and CTFFR results are present in one third of patients. The use of both the CRS and CCTA as the prior risk synergistically maximized the accuracy of the accuracy of the CTFFR technique.

Long-term all-cause mortality among asymptomatic individuals with 80th percentile of coronary calcium score based on age and gender in the St. Francis Heart Study.

OBJECTIVES: High coronary artery calcium score (CAC) is a significant risk factor for cardiovascular morbidity and mortality. We investigated the long-term outcome of subjects with elevated CAC. METHODS: We studied 1005 participants of The St. Francis Heart Study who were asymptomatic and apparently healthy and had CAC scores at 80th percentile or higher for age and gender. They were randomized to receive atorvastatin 20 mg daily or placebo for up to 5 years. We used an as-treated study design accounting for cross-overs at the end of the original trial. All-cause mortality risk was assessed using adjusted hazard ratios. RESULTS: Mean age was 59 ± 6 years and 26% (N = 263) were female. After 17 ± 3 years follow-up 176 subjects died. High CAC at baseline was associated with increased mortality risk with adjusted hazard ratio for logarithmic transformed CAC at 1.33 and 95% confidence interval 1.06-1.68. The mortality risk associated with CAC was similar between the group with high-sensitivity CRP ≥2 and <2 mg/dL. Those with a family history of premature coronary artery disease exhibited a higher mortality risk in association with high CAC with an adjusted hazard ratio 1.51 (1.09, 2.09). CONCLUSION: Elevated CAC is an independent risk for long-term all-cause mortality. The screening of CAC score in addition to identifying conventional risk factors can differentiate asymptomatic individuals with and without increased long-term mortality risk.

Reduced cardiac function is associated with cardiac injury and mortality risk in hospitalized COVID-19 Patients.

BACKGROUND: Cardiac injury is common in COVID-19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID-19 patients. HYPOTHESIS: The aim of this study was to assess cardiac function among COVID-19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function. METHODS/RESULTS: This retrospective cohort study analyzed 143 consecutive COVID-19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin-I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin-I elevation, 42% with mild troponin increase (0.04-5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in-hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96). CONCLUSIONS: Reduced cardiac function is highly prevalent among hospitalized COVID-19 patients with biomarkers of myocardial injury and is independently associated with mortality.

Soluble ST2 is associated with all-cause and cardiovascular mortality in a population-based cohort: the Dallas Heart Study.

BACKGROUND: ST2, part of the interleukin-1 receptor family, is released from cardiac myocytes under mechanical strain. Soluble ST2 (sST2) concentrations are associated with adverse cardiac events in high-risk cohorts. We evaluated the association of sST2 with all-cause and cardiovascular mortality in a large, low-risk population-based cohort. METHODS: Plasma sST2 was measured in 3294 subjects from the Dallas Heart Study, a probability-based population cohort. We categorized participants into undetectable (reference group) or quartiles of detectable sST2 concentrations. Associations with all-cause and cardiovascular mortality were assessed over a median 8.3 years of follow-up. RESULTS: sST2 concentrations were not significantly associated with most traditional risk factors, prevalent subclinical cardiovascular disease, or nonfatal cardiac events. However, a higher proportion of African Americans had detectable concentrations of sST2 than non-African Americans (44% vs 21%, respectively, P < 0.0001). In addition, sST2 concentrations were significantly associated with markers of inflammation. Increased sST2 was associated with increased all-cause mortality (Ptrend ≤ 0.0001) and cardiovascular mortality (Ptrend = 0.0004). In fully adjusted models, those in the highest quartile of detectable sST2 were at increased risk for all-cause death compared to those with undetectable sST2 concentrations (adjusted hazard ratio 2.1, 95% CI 1.4-3.2, P = 0.0009). CONCLUSIONS: In a low-risk population, sST2 does not associate with traditional cardiovascular risk factors or nonfatal cardiovascular events but is higher in African Americans and is associated with increased all-cause and cardiovascular mortality. Further investigation is needed regarding the role of sST2 in risk prediction, particularly among African Americans.

Race-specific associations of myeloperoxidase with atherosclerosis in a population-based sample: the Dallas Heart Study.

OBJECTIVE: Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population. METHODS AND RESULTS: Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08-1.84), APB (beta coefficient 0.23, p = 0.02), and AWT (beta coefficient 0.04, p = 0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61-1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (p(interaction) = 0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23-2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68-1.44). CONCLUSION: Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease.