Comparison of coronary atherosclerotic plaque progression in East Asians and Caucasians by serial coronary computed tomographic angiography: A PARADIGM substudy.

OBJECTIVES: To investigate potential differences in plaque progression (PP) between in East Asians and Caucasians as well as to determine clinical predictors of PP in East Asians. BACKGROUND: Studies have demonstrated differences in cardiovascular risk factors as well as plaque burden and progression across different ethnic groups. METHODS: The study comprised 955 East Asians (age 60.4 â€‹± â€‹9.3 years, 50.9% males) and 279 Caucasians (age 60.4 â€‹± â€‹8.6 years, 74.5% males) who underwent two serial coronary computed tomography angiography (CCTA) studies over a period of at least 24 months. Patients were enrolled and analyzed from the PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging) registry. After propensity-score matching, plaque composition and progression were compared between East Asian and Caucasian patients. Within East Asians, the plaque progression group (defined as plaque volume at follow-up CCTA minus plaque volume at baseline CCTA> 0) was compared to the no PP group to determine clinical predictors for PP in East Asians. RESULTS: In the matched cohort, baseline volumes of total plaque as well as all plaque subtypes were comparable. There was a trend towards increased annualized plaque progression among East Asians compared to Caucasians (18.3 â€‹± â€‹24.7 â€‹mm3/year vs 16.6 â€‹mm3/year, p â€‹= â€‹0.054). Among East Asians, 736 (77%) had PP. East Asians with PP had more clinical risk factors and higher plaque burden at baseline (normalized total plaque volume of144.9 â€‹± â€‹233.3 â€‹mm3 vs 36.6 â€‹± â€‹84.2 â€‹mm3 for PP and no PP, respectively, p â€‹< â€‹0.001). Multivariate logistic regression analysis showed that baseline normalized plaque volume (OR: 1.10, CI: 1.10-1.30, p â€‹< â€‹0.001), age (OR: 1.02, CI: 1.00-1.04, p â€‹= â€‹0.023) and body mass index (OR: 2.24, CI: 1.01-1.13, p â€‹= â€‹0.024) were all predictors of PP in East Asians. Clinical events, driven mainly by percutaneous coronary intervention, were higher among the PP group with a total of 124 (16.8%) events compared to 22 (10.0%) in the no PP group (p â€‹= â€‹0.014). CONCLUSION: East Asians and Caucasians had comparable plaque composition and progression. Among East Asians, the PP group had a higher baseline plaque burden which was associated with greater PP and increased clinical events.

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy.

AIMS: To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques. CONCLUSION: Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.

Abnormal Fractional Flow Reserve in Nonobstructive Coronary Artery Disease.

Background The basis of discordance between invasive coronary angiographic (ICA) anatomic stenosis and fractional flow reserve (FFR) is not fully understood. We analyzed coronary computed tomography angiography (CTA) characteristics of ICA-verified nonobstructive lesions in the proximal or midleft anterior descending artery with FFR ≤0.8, that is, anatomy-physiology mismatch. Methods and Results CTA and ICA were performed in 108 patients. FFR was measured during intravenous ATP (180 µg/[kg·min]) infusion. CTA-verified plaque characteristics between 53 consecutive ICA-FFR mismatch (ICA-quantitative coronary angiography <50%, FFR≤0.8) and 55 ICA-FFR match (ICA-quantitative coronary angiography<50%, FFR>0.8) vessels were compared. CTA-verified vessel area (20.7±6.7 versus 16.9±4.8 mm2; P=0.0007), positive area remodeling index (ARI; 1.38±0.23 versus 1.06±0.11; P<0.0001), %plaque area (64.7±12.7 versus 57.4±8.5%; P<0.0007), jeopardized myocardial mass (46.2±18.5 versus 37.1±14.3 g; P= 0.006), and the prevalence of low attenuation plaque (45.3% versus 9.1%; P<0.0001) at the minimum lumen area were significantly higher in the ICA-FFR mismatch than the match group. By receiver operation curve analysis, the areas under the curve for positive area remodeling index, %plaque area and jeopardized myocardial mass were 0.921, 0.681, and 0.641, respectively, for the diagnosis of mismatch (cutoff values 1.13, 66% and 58.7 g, respectively). The sensitivity and specificity of area remodeling index >1.13 for predicting ICA-FFR mismatch were 88.7% and 78.2%, respectively. Conclusions In the absence of anatomically significant stenosis, abnormal FFR is more frequently encountered in patients with CTA-derived positive remodeling, larger plaque burden, and low attenuation plaque. These findings contribute to a better understanding of how FFR-based decision-making might translate into demonstrated superior clinical outcomes.

Prognosis of CT-derived Fractional Flow Reserve in the Prediction of Clinical Outcomes.

PURPOSE: To examine the prognostic implication of fractional flow reserve (FFR) derived from coronary CT (FFRCT) in routine clinical practice. MATERIALS AND METHODS: Patients referred for FFRCT analysis at a single center between October 2015 and June 2017 were retrospectively included and followed up for rates of invasive angiography and clinical events. Two hundred seven patients underwent successful FFRCT analysis with seven lost to follow-up, leaving 200 (mean age ± standard deviation, 62.4 years ± 10.0; 49 [24.5%] women) patients for analysis. At coronary CT angiography, patients were categorized as having significant stenosis (SS) in the presence of a diameter stenosis greater than or equal to 50% (hereafter, SS positive) and flow limitation in the presence of a postlesion (that is, FFRCT measured 2 cm to the distal aspect of the lesion) FFRCT less than 0.80 (hereafter, FFRCT positive). Vessel-oriented clinical events (VOCEs) were defined as vessel-related late revascularization (>90 days), myocardial infarction, and cardiac mortality. RESULTS: At CT angiography, 130 (65%) studies were SS positive and 63 (31.5%) were FFRCT positive. At median follow-up of 477 days (range, 252-859 days), there were 26 VOCE end points in 22 patients: 22 revascularizations and four nonfatal myocardial infarctions. VOCE end points occurred in zero of 58 (0%) of SS-negative and FFRCT negative patients, in eight of 79 (10.1%) of SS-positive and FFRCT-negative patients, in zero of 12 (0%) of SS-negative and FFRCT-positive patients, and in 18 of 51 (35.3%) of SS-positive and FFRCT-positive patients (log-rank χ2 = 30.1; P < .001). At multivariable Cox regression, both FFRCT (hazard ratio per 0.1 decrease, 1.54 [95% confidence interval: 1.1, 2.2] P = .013) and stenosis (hazard ratio per unit increase, 2.16 [95% confidence interval: 1.25, 3.72] P = .006) were independently associated with VOCE. CONCLUSION: Stenosis and FFRCT are independent predictors of intermediate-term outcomes. In the absence of a stenosis greater than 50%, a positive FFRCT result is not associated with an increased intermediate risk.© RSNA, 2019Supplemental material is available for this article.See also commentary by Fairbairn and Bull in this issue.

Guiding Therapy by Coronary CT Angiography Improves Outcomes in Patients With Stable Chest Pain.

BACKGROUND: Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint). OBJECTIVES: This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint. METHODS: In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies. RESULTS: Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size. CONCLUSIONS: The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy.

BACKGROUND: The aim of the study is examine the impact of non-obstructive (<50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA). METHODS: CTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque. RESULTS: Of 944 (62 ±â€¯9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8 ±â€¯221mm3 versus 72.9 ±â€¯84.3mm3, p < 0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, p < 0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5 ±â€¯31.4mm3/yr versus 14.9 ±â€¯20.1mm3/yr, p < 0.001) and calcified plaque volume (17 ±â€¯24mm3/yr versus 7 ±â€¯11mm3/yr, p < 0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components. CONCLUSION: The presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.

Post-vaccination myositis and myocarditis in a previously healthy male.

BACKGROUND: The immunological literature has been redefining clinical phenomena as hypotheses emerge regarding causal links between triggers, immunologic manifestations, and their specific inflammatory cascades. Of late, autoimmune manifestations that appear to be caused by an external adjuvant have been grouped into a complex syndrome referred to as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This syndrome may present with diverse clinical problems, which may include neurocognitive impairment, inflammatory musculoskeletal changes, and constitutional symptoms. There is evidence in the literature linking vaccines to different auto-immune manifestations. Vaccines have not traditionally been reported to trigger ASIA, although reports are emerging linking the human papilloma virus and hepatitis B vaccines to it. CASE PRESENTATION: We report the first suspected case of ASIA in a previously healthy patient who received the Fluad seasonal influenza vaccine, which contains the MF59 adjuvant. He presented to hospital with profound weakness and was diagnosed with severe rhabdomyolysis. He also had elevated troponin-I and extensive cardiac investigations enabled the diagnosis of myocarditis. His infectious and rheumatologic work-ups were negative. He responded well to conservative management and did not require immune suppressive therapy. CONCLUSION: Given the benefits of the influenza vaccine, and the low incidence of clinically significant complications, we encourage ongoing seasonal influenza immunization. However, ongoing surveillance is required to evaluate the occurrence of rare adverse events, including ASIA.