CT or Invasive Coronary Angiography in Stable Chest Pain.

BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Coronary Artery Calcium Score Predicts Major Adverse Cardiovascular Events in Stable Chest Pain.

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

Assessing the Impact of Long-Term High-Dose Statin Treatment on Pericoronary Inflammation and Plaque Distribution-A Comprehensive Coronary CTA Follow-Up Study.

Computed tomography angiography (CTA) has validated the use of pericoronary adipose tissue (PCAT) attenuation as a credible indicator of coronary inflammation, playing a crucial role in coronary artery disease (CAD). This study aimed to evaluate the long-term effects of high-dose statins on PCAT attenuation at coronary lesion sites and changes in plaque distribution. Our prospective observational study included 52 patients (mean age 60.43) with chest pain, a low-to-intermediate likelihood of CAD, who had documented atheromatous plaque through CTA, performed approximately 1 year and 3 years after inclusion. We utilized the advanced features of the CaRi-Heart® and syngo.via Frontier® systems to assess coronary plaques and changes in PCAT attenuation. The investigation of changes in plaque morphology revealed significant alterations. Notably, in mixed plaques, calcified portions increased (p < 0.0001), while non-calcified plaque volume (NCPV) decreased (p = 0.0209). PCAT attenuation generally decreased after one year and remained low, indicating reduced inflammation in the following arteries: left anterior descending artery (LAD) (p = 0.0142), left circumflex artery (LCX) (p = 0.0513), and right coronary artery (RCA) (p = 0.1249). The CaRi-Heart® risk also decreased significantly (p = 0.0041). Linear regression analysis demonstrated a correlation between increased PCAT attenuation and higher volumes of NCPV (p < 0.0001, r = 0.3032) and lipid-rich plaque volume (p < 0.0001, r = 0.3281). Our study provides evidence that high-dose statin therapy significantly reduces CAD risk factors, inflammation, and plaque vulnerability, as evidenced by the notable decrease in PCAT attenuation, a critical indicator of plaque progression.

Coronary Computed Tomography Angiography-Derived Modified Duke Index Is Associated with Peri-Coronary Fat Attenuation Index and Predicts Severity of Coronary Inflammation.

Background and Objectives: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary stenosis. However, it does not take into consideration the presence or severity of peri-coronary inflammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors, and peri-coronary inflammation in the coronary arteries of patients with coronary artery disease. Materials and Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1-patients with low index, ≤3 (n = 107), and group 2-patients with high index, >3 (n = 65). Demographic, clinical, and CCTA data were collected for all patients, and FAI analysis of coronary inflammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia, or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score, 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, 13.26 ± 10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84% ± 25.86% vs. 16.87% ± 15.80%; p < 0.0001). ROC analysis identified a cut-off value of 12.1% of the CaRi-Heart® risk score for predicting a high severity of coronary lesions, with an AUC of 0.69. Conclusions: The CT-derived modified Duke index correlates well with local perilesional inflammation as assessed using the FAI score at different levels of the coronary circulation.

Impact of smoking in patients with suspected coronary artery disease in the randomised DISCHARGE trial.

OBJECTIVES: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. MATERIALS AND METHODS: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). RESULTS: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. CONCLUSION: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. CLINICAL RELEVANCE STATEMENT: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400229. KEY POINTS: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers.

The Association between Apolipoprotein B, Cardiovascular Risk Factors and Subclinical Atherosclerosis-Findings from the SEPHAR National Registry on Hypertension in Romania.

The present study aimed to investigate the association between apolipoprotein B (Apo B) and classical features associated with clinical or subclinical atherosclerosis. A total of 811 adult patients from the general Romanian population, included in the national SEPHAR registry on hypertension, were divided into two groups based on Apo B value (low versus high Apo B with a cut-off established at 130 mg/dL) and subsequently into four subgroups according to the cut-offs recommended by the 2021 ESC Guidelines on Cardiovascular Disease Prevention. In all patients, lipid profile, uric acid, full blood count and presence of significant carotid plaques were assessed. Apo B levels were positively correlated with proatherogenic lipids (total cholesterol, triglycerides and LDL-cholesterol, p < 0.0001) and negatively correlated with HDL cholesterol (all p < 0.05). In comparison with patients with low Apo B levels, those with elevated Apo B levels more frequently presented significant carotid plaques (17% vs. 19% vs. 28% vs. 46%, p < 0.0001). Univariate regression analysis identified a strong association between the level of uric acid and increased value of Apo B in the four subgroups (uric acid 4.8 +/- 1.3 vs. 5 +/- 1.6 vs. 5.1 +/- 1.5 vs. 5.8 +/- 1.6, r = 0.2, p < 0.0001). The results of this nationwide registry on hypertension in Romania indicate that high Apo B may be considered as a risk factor for CVD, promoting atherosclerosis and associated with increased expression of classical markers of clinical or subclinical CVD.

Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.

What Patients Find on the Internet When Looking for Information About Percutaneous Coronary Intervention: Multilanguage Cross-sectional Assessment.

BACKGROUND: The internet provides general users with wide access to medical information. However, regulating and controlling the quality and reliability of the considerable volume of available data is challenging, thus generating concerns about the consequences of inaccurate health care-related documentation. Several tools have been proposed to increase the transparency and overall trustworthiness of medical information present on the web. OBJECTIVE: We aimed to analyze and compare the quality and reliability of information about percutaneous coronary intervention on English, German, Hungarian, Romanian, and Russian language websites. METHODS: Following a rigorous protocol, 125 websites were selected, 25 for each language sub-sample. The websites were assessed concerning their general characteristics, compliance with a set of eEurope 2002 credibility criteria, and quality of the informational content (namely completeness and accuracy), based on a topic-specific benchmark. Completeness and accuracy were graded independently by 2 evaluators. Scores were reported on a scale from 0 to 10. The 5 language subsamples were compared regarding credibility, completeness, and accuracy. Correlations between credibility scores on the one hand, and completeness and accuracy scores, on the other hand, were tested within each language subsample. RESULTS: The websites' compliance with credibility criteria was average at best with scores between 3.0 and 6.0. In terms of completeness and accuracy, the website subsets qualified as poor or average, with scores ranging from 2.4 to 4.6 and 3.6 to 5.3, respectively. English language websites scored significantly higher in all 3 aspects, followed by German and Hungarian language websites. Only German language websites showed a significant correlation between credibility and information quality. CONCLUSIONS: The quality of websites in English, German, Hungarian, Romanian, and Russian languages about percutaneous coronary intervention was rather inadequate and may raise concerns regarding their impact on informed decision-making. Using credibility criteria as indicators of information quality may not be warranted, as credibility scores were only exceptionally correlated with content quality. The study brings valuable descriptive data on the quality of web-based information regarding percutaneous coronary intervention in multiple languages and raises awareness about the need for responsible use of health-related web resources.

Correction to: Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

An amendment to this paper has been published and can be accessed via the original article.

Health-related qualify of life, angina type and coronary artery disease in patients with stable chest pain.

BACKGROUND: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. METHODS: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. RESULTS: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type. CONCLUSIONS: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02400229.

Modern Concepts in Regenerative Therapy for Ischemic Stroke: From Stem Cells for Promoting Angiogenesis to 3D-Bioprinted Scaffolds Customized via Carotid Shear Stress Analysis.

Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, neuroprotection and neurorecovery. Therapeutic angiogenesis also seems to represent a promising tool to improve the prognosis of cerebral ischemia. This review aims to present the modern concepts and the current status of regenerative therapy for ischemic stroke and discuss the main results of major clinical trials addressing the effectiveness of stem cell therapy for achieving neuroregeneration in ischemic stroke. At the same time, as a glimpse into the future, this article describes modern concepts for stroke prevention, such as the implantation of bioprinted scaffolds seeded with stem cells, whose 3D geometry is customized according to carotid shear stress.

Genetic Approaches to the Study of Gene Variants and Their Impact on the Pathophysiology of Type 2 Diabetes.

Diabetes mellitus is an incurable progressive disease, characterized by elevated blood glucose levels, which lead to the development of micro- and macrovascular complications. Although the etiopathology of the disease remains unclear, it seems to be multifactorial, with an important interaction between genetics and environmental causes. Currently, the genetics of type 2 diabetes (T2D) is poorly understood. The recent advance of the genetic technologies and with a better understanding of genetics, more than 120 distinct genetic loci, with more than 150 variants, have been identified that may be involved in the pathogenesis of T2D. However, as these variants can account for only approximately 20% of the heritability of T2D, there is an obvious need for additional approaches to identify susceptibility genes or genetic mechanisms involved in the development of this disease. There is a growing number of genes found to be related to T2D; however, their individual impact on the pathogenesis of the disease appears to be low, while silencing of protective genes may also contribute to the development of this disease. The present review attempts to summarize our current knowledge in the field of genetics of T2D, highlighting the possible practical applications for each approach.

Epigenetic Modifications Linked to T2D, the Heritability Gap, and Potential Therapeutic Targets.

With the pandemic of type 2 diabetes (T2D), there is an ever-increasing need to fully understand the underlying mechanisms of the disease. Type 2 diabetes shows a high heritability risk (25-80%); however, genes account only for 10% of this risk. From all the risk factors for diabetes, epigenetic mechanisms have the highest statistical scoring in explaining the disease. A multitude of organ-specific epigenomic changes have been linked to type 2 diabetes. Nutritional influences, mainly in the early life, physical activity level, environmental toxins act as epigenetic factors and the recognized epigenetic changes can represent a therapeutical target, new drugs being currently in development for this application. Our current review focuses on the most common epigenetic modifications linked to type 2 diabetes or insulin resistance, the potentially emerging epigenetic-related interventions and pharmacoepigenetic knowledge.

High iliac calcium score is associated with increased severity and complexity of peripheral arterial disease and predicts global atherosclerotic burden.

BACKGROUND: The role of vascular calcifications in iliac arteries for predicting global atherosclerotic burden in still unknown. The aim of this study was to investigate whether iliac calcium score (ICS), a new computed tomographic angiography (CTA) derived biomarker of vascular calcification, can predict the severity and complexity of peripheral arterial disease (PAD) as well as the global atherosclerotic burden. PATIENTS AND METHODS: This was a single centre, non-randomized, observational prospective study on 84 consecutive patients with symptomatic peripheral arterial disease, undergoing peripheral CTA examination of the lower limbs, divided into high (n = 42) and low ICS (n = 42) groups with a median value for ICS of 3934 HU. RESULTS: Patients with high ICS were significantly older (66.2 ± 8.0 vs. 62.8 ± 11.2, p < 0.0001) and were more frequently diabetic (61.9 vs. 38.1 %, p = 0.04). ICS was significantly higher in patients with Rutherford stage 5-6 vs. 1-2 (p = 0.03) and in TASC D or TASC C vs. TASC B class (p = 0.01). Mean iliac intima-media thickness (i-IMT) was significantly higher in the high ICS group compared to the low ICS group (1.3 ± 0.2 vs. 0.9 ± 0.2, p < 0.0001). Linear regression analysis demonstrated a very good correlation between ICS and i-IMT (r = 0.59, p < 0.0001 for right, r = 0.57, p < 0.0001 for left and r = 0.67, p < 0.0001 for both iliac arteries averaged). Patients with high ICS presented a significantly lower left ventricular ejection fraction compared to those with low ICS (45.3 ± 4.3 vs. 53.8 ± 4.8, p < 0.0001). Linear regression analysis demonstrated significant inverse correlation between ICS and left ventricular EF (r = -0.54, p < 0.0001). CONCLUSIONS: Increased values of ICS, a new CTA marker of vascular calcification, are associated with a higher severity and complexity of PAD and a more depressed left ventricular function. High ICS values are also associated with increased i-IMT. Both can represent new surrogate markers of an increased atherosclerotic burden.

Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

RATIONALE: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. OBJECTIVE: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). METHODS AND RESULTS: The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. CONCLUSIONS: This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591.

Genetics of Congenital Heart Disease: Past and Present.

Congenital heart disease is the most common congenital anomaly, representing an important cause of infant morbidity and mortality. Congenital heart disease represents a group of heart anomalies that include septal defects, valve defects, and outflow tract anomalies. The exact genetic, epigenetic, or environmental basis of congenital heart disease remains poorly understood, although the exact mechanism is likely multifactorial. However, the development of new technologies including copy number variants, single-nucleotide polymorphism, next-generation sequencing are accelerating the detection of genetic causes of heart anomalies. Recent studies suggest a role of small non-coding RNAs, micro RNA, in congenital heart disease. The recently described epigenetic factors have also been found to contribute to cardiac morphogenesis. In this review, we present past and recent genetic discoveries in congenital heart disease.

Deformation pattern and predictive value of right ventricular longitudinal strain in children with pulmonary arterial hypertension.

BACKGROUND: Right ventricular function has been identified as an important prognostic factor in children with pulmonary arterial hypertension. The aim of the study was to assess the deformation pattern and prognostic value of right ventricular longitudinal strain in children with pulmonary arterial hypertension. METHODS: We prospectively evaluated 46 children (25 with pulmonary arterial hyperetension and 21 age and sex matched controls) using conventional and speckle-tracking echocardiography, brain natriuretic peptide levels and clinical status expressed by WHO functional class and 6-min walking test. According to the clinical status after 12 months of follow-up, the pulmonary arterial hypertension patients were divided in two groups: non-worsening (13) and worsening (12). RESULTS: Right ventricular free wall longitudinal strain and strain rate were significantly lower in children with PAH compared with controls (-24.72 ± 3.48 vs -15.60 ± 3.40, p = 0.0001 and -1.44 ± 0.09 vs -1.09 ± 0.15, p = 0.0001, respectively). There was a more expressed decrease of basal than apical region of right ventricular free wall longitudinal strain/strain rate in pulmonary arterial hypertension patients compared with controls (strain: p = 0.0001 vs p = 0.07 and strain rate: p = 0.0001 vs p = 0.002). Comparing worsening and non-worsening pulmonary arterial hypertension patients there was a significant difference in Mid right ventricular free wall longitudinal strain (-14.00 ± 3.13 vs. -20.76 ± 4.62, p = 0.0001). In multivariable logistic regression analysis Mid right ventricular free wall longitudinal strain was an independent predictor of worsening in pulmonary arterial hypertension children (OR 0.45; 95 % CI: 0.21-0.96, p = 0.041). In ROC curve analysis a cut-off value of Mid right ventricular free wall longitudinal strain of -18.50 % predicted clinical worsening in pulmonary arterial hypertension children, with a sensitivity and specificity of 91.7 and 30.8 %, respectively (area under curve = 0.88 ± 0.06, 95 % CI: 0.75-1.00, p = 0.001). CONCLUSIONS: Two-dimensional speckle-tracking echocardiography is a complementary non-invasive tool for assessment of right ventricular function in children with severe pulmonary arterial hypertension, allowing also clinical prediction and segmental analysis of right ventricular myocardial performance in these patients.

Three Rare Anomalies of the Large Vessels in an Infant with Tetralogy of Fallot.

Isolated left subclavian artery (LSA) from the pulmonary artery (PA) is a very rare vascular anomaly. We report a case of abnormal origin of the LSA from the PA via a very large ductus arteriosus (DA) in association with a rare communication between the left common carotid artery (LCCA) and the LSA in a patient with tetralogy of Fallot. doi: 10.1111/jocs.12770 (J Card Surg 2016;31:461-463).

Aneurysmal aorto-left ventricular tunnel causing right ventricular outflow tract obstruction, associated with bicuspid aortic valve.

We report the case of a newborn with an aneurysmal aorto-left ventricular tunnel causing significant paravalvular aortic regurgitation and obstruction of the right ventricular outflow tract (RVOT), coexisting with a bicuspid aortic valve. The coexistence of the two malformations together with the obstruction of the RVOT is very rare. In this case, the prompt diagnosis and surgery led to significant improvement of the clinical status and to recovery of the left ventricular function (increase of the ejection fraction from 21 to 41 %), underlining the importance of early diagnosis in this rare malformation.

Plaque quantification by coronary CT and intravascular ultrasound identifies a low CT density core as a marker of plaque instability in acute coronary syndromes.

The purpose of this study was to demonstrate the relationship between the presence and amount of a low-density core (LDC) with a CT density < 30 Hounsfield units (HU) by coronary computed tomography angiography (CCTA) and IVUS-derived markers of vulnerability in the culprit lesions (CL) of patients with acute coronary syndromes (ACS).In 43 patients with ACS, 105 coronary plaques were scanned using CCTA and IVUS for the quantitative and qualitative assessment of vulnerability markers.The presence of a low attenuation plaque (LAP) was identified in 67.4% of the CL and 29.03% of the non-CL (P = 0.0001). The presence of a LDC > 6.0 mm(3) was significantly correlated with the percentage of the necrotic core (NC) (22.08% versus 7.97%, P = 0.001) and the fibro-fatty tissue by IVUS (18.68% versus 15.87%, P = 0.02). LDC volumes showed a good correlation with the percentage of the NC (r = 0.7303, P < 0.0001) and the fibro-fatty tissue in the CL (r = 0.4928, P < 0.0008). Quantitative plaque analysis revealed a significant difference in plaque composition between CL and non-CL in regards to the LDC (18.45 versus 6.5, P < 0.001), the percentage of NC (20.74 versus 18.74, P = 0.02), fibro-fatty tissue (17.77 versus 15.48, P = 0.002), and fibrotic tissue (51.68 versus 54.8, P = 0.01).VH-IVUS and CCTA plaque quantification showed that the presence of a low-density (< 30 HU) core within the CL of patients with ACS represents a marker of vulnerability and correlates well with other CCTA and IVUS-derived features of vulnerability, particularly the NC of the plaque.