Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

OBJECTIVES: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. METHODS: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. RESULTS: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. CONCLUSIONS: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. CLINICAL RELEVANCE STATEMENT: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. KEY POINTS: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Association Between the Magnitude of Glycemic Control and Body Weight Loss With GLP-1 Receptor Agonists and Risk of Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-analyses of Randomized Diabetes Cardiovascular Outcomes Trials.

PURPOSE: Reduction of major atherosclerotic cardiovascular events (MACE) has not been consistent among different glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess the association between the magnitude of glycemic control, body weight loss, and reductions in systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) achieved through GLP-1 RA therapy and MACE. METHODS: Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through March 2023. Studies were eligible if they were cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs versus placebo in T2DM patients. The outcome of interest was 3-point MACE - cardiovascular death, myocardial infarction, or stroke. Random-effects meta-regression analyses evaluated the associations between reductions of HbA1c, body weight, SBP and LDL-C and reduction of MACE. RESULTS: Overall, 8 CVOTs were included (60079 patients, 30693 with GLP-1 RAs). Reductions of HbA1C were associated with the reduction of 3P-MACE (Log RR -0.290 [95% CI -0.515;-0.064], p = 0.012), with an estimated RR reduction of 25% for each 1% absolute reduction in HbA1C levels. Body weight loss was associated with the reduction of 3P-MACE (Log RR -0.068 [95% CI -0.135;-0.001], p = 0.047), with an estimated RR reduction of 7% for each 1 kg reduction in body weight. Reductions of SBP (Log RR -0.058 [95% CI -0.192;0.076], p = 0.396) and LDL-C (Log RR -0.602 [95% CI -4.157;2.953], p = 0.740) were not associated with the reduction of 3P-MACE. CONCLUSIONS: In T2DM patients, more potent GLP-1 RAs in reducing HbA1c and body weight were associated with greater reductions of MACE.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Patients With and Without Diabetes: Long-Term Outcomes From the CONFIRM Registry.

BACKGROUND: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known. METHODS: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis). RESULTS: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879). CONCLUSION: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.

BACKGROUND: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. METHODS: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV). RESULTS: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (ß: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017). CONCLUSION: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Severe hypoxemia in a patient with right ventricular myocardial infarction and SARS-CoV-2 infection.

BACKGROUND: Refractory hypoxemia after right ventricular myocardial infarction and concomitant SARS-CoV-2 infection represents an uncommon, yet particularly challenging clinical scenario. We report a challenging diagnostic case of refractory hypoxemia due to right-to-left shunt highlighting contemporary challenges and pitfalls in acute cardiovascular care associated with the current COVID-19 pandemic. CASE PRESENTATION: A 52-year-old patient admitted for inferior acute myocardial infarction developed rapidly worsening hypoxemia shortly after primary percutaneous coronary intervention. RT-PCR screening for SARS-CoV-2 was positive, even though the patient had no prior symptoms. A computed tomography pulmonary angiogram excluded pulmonary embolism and showed only mild interstitial pulmonary involvement of the virus. Transthoracic echocardiogram showed severe right ventricular dysfunction and significant right-to-left shunt at the atrial level after agitated saline injection. Progressive improvement of right ventricular function allowed weaning from supplementary oxygen support. Patient was latter discharged with marked symptomatic improvement. CONCLUSION: Refractory hypoxemia after RV myocardial infarction should be carefully addressed, even in the setting of other more common and tempting diagnoses. After exclusion of usual etiologies, right-to-left shunting at the atrial level should always be suspected, as this may avoid unnecessary and sometimes harmful interventions.

Association between Aortic Valve Calcification Progression and Coronary Atherosclerotic Plaque Volume Progression in the PARADIGM Registry.

Background Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary -artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies. Purpose To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations. Materials and Methods A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed. Results Overall, 594 participants (mean age ± standard deviation, 62 years ± 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years ± 1.5). At baseline, the AVC score was 31 Agatston units ± 117, and the normalized total plaque volume at baseline was 122 mm3 ± 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized ß = 0.24; 95% CI: 0.16, 0.32; P < .001) and both calcified (ß = 0.26; 95% CI: 0.18, 0.34; P < .001) and noncalcified (ß = 0.17; 95% CI: 0.08, 0.25; P < .001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (ß = 0.13; 95% CI: 0.03, 0.22; P = .01), driven solely by calcified plaque volume (ß = 0.24; 95% CI: 0.14, 0.34; P < .001) but not noncalcified plaque volumes (ß = -0.06; 95% CI: -0.14, 0.03; P = .17). Conclusion The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. Clinical trial registration no. NCT02803411 © RSNA, 2021 See also the editorial by Sinitsyn in this issue.

Surgical versus transcatheter aortic valve replacement in low-risk patients: A long-term propensity score-matched analysis.

BACKGROUND: Recent studies suggest the use of transcatheter aortic valve implantation (TAVI) as an alternative to surgical aortic valve replacement (SAVR) in lower risk populations, but real-world data are scarce. METHODS: Single-center retrospective study of patients undergoing SAVR (between June 2009 and July 2016, n = 682 patients) or TAVI (between June 2009 and July 2017, n = 400 patients). Low surgical risk was defined as EuroSCORE II (ES II) < 4% for single noncoronary artery bypass graft procedure. TAVI patients were propensity score-matched in a 1:1 ratio with SAVR patients, paired by age, New York Heart Association class, diabetes mellitus, chronic obstructive pulmonary disease, atrial fibrillation, creatinine clearance, and left ventricular ejection fraction < 50%. RESULTS: A total of 158 patients (79 SAVR and 79 TAVI) were matched (mean age 79 ± 6 years, 79 men). TAVI patients had a higher incidence of permanent pacemaker implantation (0% vs. 19%, p < 0.001) and more than mild paravalvular leak (4% vs. 18%, p = 0.009), but comparable rates of stroke, major or life-threatening bleeding, emergent cardiac surgery, new-onset atrial fibrillation, and need for renal replacement therapy. Hospital length-of-stay and 30-day mortality were similar. At a median follow-up of 4.5 years (IQR 3.0-6.9), treatment strategy did not influence all-cause mortality (HR 1.19, 95% CI 0.77-1.83, log rank p = 0.43) nor rehospitalization (crude subdistribution HR 1.56, 95% CI 0.71-3.41, p = 0.26). ES II remained the only independent predictor of long-term all-cause mortality (adjusted HR 1.40, 95% CI 1.04-1.90, p = 0.029). CONCLUSION: In this low surgical risk severe aortic stenosis population, we observed similar rates of 30-day and long-term all-cause mortality, despite higher rates of permanent pacemaker implantation and more than mild paravalvular leak in TAVI patients. The results of this small study suggest that both procedures are safe and effective in the short-term, while the Heart Team remains essential to assess both options on the long-term.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry.

BACKGROUND: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA). METHODS: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year. RESULTS: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors. CONCLUSION: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.

Subclinical coronary artery disease in veteran athletes: is a new preparticipation methodology required?

OBJECTIVE: Preparticipation evaluation of veteran athletes should focus on accurate cardiovascular (CV) risk stratification and subclinical detection of coronary artery disease (CAD), which is the main cause of sudden cardiac death in this population. We aimed to investigate the effectiveness of current preparticipation methodology used to identify veteran athletes with high coronary atherosclerotic burden. METHODS: A total of 105 asymptomatic male athletes aged ≥40 years old, with low to moderate CV risk (Systematic Coronary Risk Estimation <5%) who trained ≥4 hours/week for at least 5 years, were studied. The screening protocol included clinical evaluation, ECG, transthoracic echocardiogram and exercise testing. Cardiac CT was performed to detect CAD, defined as a high atherosclerotic burden according to coronary artery calcium score and coronary CT angiography. RESULTS: The majority of the athletes (n=88) engaged in endurance sports, with a median volume of exercise of 66 (44; 103) metabolic equivalent task score/hour/week. Exercise testing was abnormal in 13 (12.4%) athletes, 6 (5.7%) with electrocardiographic criteria for myocardial ischaemia and 7 (6.7%) with exercise-induced ventricular arrhythmias. A high coronary atherosclerotic burden was present in 27 (25.7%) athletes, of whom 11 (40.7%) had CV risk factors and 6 had abnormal exercise tests, including 3 who were positive for myocardial ischaemia. CONCLUSIONS: Conventional methodology used in preparticipation evaluation of veteran athletes, based on clinical CV risk factors and exercise testing, was poor at identifying significant subclinical CAD. The inclusion of more objective markers, particularly data derived from cardiac CT, is promising for more accurate CV risk stratification of these athletes.

Coronary atherosclerotic burden in veteran athletes: The relationship between cardiovascular risk and volume of exercise.

INTRODUCTION AND OBJECTIVES: The association between exercise and coronary atherosclerosis still remains unclarified. We aimed to analyze the prevalence of high coronary atherosclerotic burden in veteran athletes, considering cardiovascular (CV) risk and volume of exercise. METHODS: A total of 105 asymptomatic male veteran athletes (48±5.6 years old) were studied. A high coronary atherosclerotic burden was defined as one of the following characteristics in coronary computed tomography angiography: calcium score >100, >75th percentile, obstructive plaques, involving left main, three-vessels or two-vessels including proximal anterior descending artery, segment involvement score >5 or CT-adapted Leaman score ≥5. CV risk was stratified by SCORE2 and volume of exercise by metabolic equivalent task score. RESULTS: Most athletes (n=88) were engaged in endurance sports for 17.1±9.8 years, with a median exercise volume of 66 [IQR 44-103] metabolic equivalent of tasks/hour/week. The mean Systematic Coronary Risk Evaluation 2 was 2.8±1.5%; 76.9% of athletes had a low-moderate risk and none a very high risk. High coronary atherosclerotic burden was present in 25.7% athletes. Athletes with high cardiovascular risk and high exercise volume (above the median) showed significantly high coronary atherosclerotic burden compared to those with low-moderate risk and high volume (50.0% vs. 15.6%; p=0.017). Among athletes with low to moderate risk, a high volume of exercise tended to be protective, while in those with low volume, there was similar rate of high coronary atherosclerotic burden, regardless of CV risk. CONCLUSIONS: A combination of higher volume of exercise and high cardiovascular risk revealed the worst association with coronary atherosclerosis in veteran athletes. The relationship between these variables is controversial, but integrating exercise characteristics and risk assessment into preparticipation evaluation is essential.