Márton Kolossváry

Serum lipids and cardiac function correlate with nitrotyrosine and MMP activity in coronary artery disease patients

Peroxynitrite‐matrix metalloproteinase (MMP) signalling has been shown to contribute to myocardial ischaemia/reperfusion injury and heart failure and to be influenced by hyperlipidaemia in preclinical models. Therefore, here we investigated the correlation between the markers of peroxynitrite–MMP signalling and hyperlipidaemia in patients with significant coronary stenosis.

Cardiac Computed Tomography Radiomics: A Comprehensive Review on Radiomic Techniques

Radiologic images are vast three-dimensional data sets in which each voxel of the underlying volume represents distinct physical measurements of a tissue-dependent characteristic. Advances in technology allow radiologists to image pathologies with unforeseen detail, thereby further increasing the amount of information to be processed. Even though the imaging modalities have advanced greatly, our interpretation of the images has remained essentially unchanged for decades. We have arrived in the era of precision medicine where even slight differences in disease manifestation are seen as potential target points for new intervention strategies. There is a pressing need to improve and expand the interpretation of radiologic images if we wish to keep up with the progress in other diagnostic areas. Radiomics is the process of extracting numerous quantitative features from a given region of interest to create large data sets in which each abnormality is described by hundreds of parameters. From these parameters datamining is used to explore and establish new, meaningful correlations between the variables and the clinical data. Predictive models can be built on the basis of the results, which may broaden our knowledge of diseases and assist clinical decision making. Radiomics is a complex subject that involves the interaction of different disciplines; our objective is to explain commonly used radiomic techniques and review current applications in cardiac computed tomography imaging.

Rationale, Design, and Methodological Aspects of the BUDAPEST-GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions)

The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST‐GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single‐center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same‐sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non–contrast‐enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non–contrast‐enhanced image slice was acquired at the level of L3‐L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3‐dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per‐patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST‐GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders.

Assessing genetic and environmental influences on epicardial and abdominal adipose tissue quantities: A classical twin study

Background/Objectives:Various adipose tissue compartments play an important role in the development of cardiometabolic diseases. The quantity of different fat compartments is influenced by genetic and environmental factors. The aim of our study was to evaluate the magnitude of genetic and environmental effects on epicardial, subcutaneous and visceral adipose tissue (EAT, SAT and VAT) quantities in a cohort of adult twin pairs.Subjects/Methods:In this cross-sectional study we investigated adult twins (57 monozygotic (MZ) and 33 dizygotic (DZ) same-gender twin pairs; 180 twin subjects). We measured EAT volume using electrocardiogram-gated native computed tomography (CT) scan of the heart, and abdominal SAT and VAT areas were quantified between the third and fourth lumbar vertebra on native CT images. We calculated genetic and environmental impact on the size of various adipose tissue compartments by analyzing co-twin correlations in MZ and DZ pairs separately, and furthermore by using genetic structural equation models.Results:In co-twin analysis, MZ twins had stronger correlations than DZ twins for EAT (rMZ=0.81, rDZ=0.32), similar to SAT and VAT quantities (rMZ=0.80, rDZ=0.68 and rMZ=0.79, rDZ=0.48, respectively). In multi-trait model fitting analysis, the overall contribution of genetic factors to EAT, SAT and VAT volumes were 80%, 78% and 70%, whereas environmental factors were 20%, 22% and 30%, respectively. Common pathway model analyses indicated that none of the EAT, SAT and VAT phenotypes was independent of the other two.Conclusions:Genetic factors have substantial influence, while environmental factors have only a modest impact on EAT volume, abdominal SAT and VAT quantities. There is a considerable amount of common genetic background influencing the quantities of all three adipose tissue compartments.

Iterative model reconstruction reduces calcified plaque volume in coronary CT angiography

OBJECTIVE To assess the impact of iterative model reconstruction (IMR) on calcified plaque quantification as compared to filtered back projection reconstruction (FBP) and hybrid iterative reconstruction (HIR) in coronary computed tomography angiography (CTA). METHODS Raw image data of 52 patients who underwent 256-slice CTA were reconstructed with IMR, HIR and FBP. We evaluated qualitative, quantitative image quality parameters and quantified calcified and partially calcified plaque volumes using automated software. RESULTS Overall qualitative image quality significantly improved with HIR as compared to FBP, and further improved with IMR (p<0.01 all). Contrast-to-noise ratios were improved with IMR, compared to HIR and FBP (51.0 [43.5-59.9], 20.3 [16.2-25.9] and 14.0 [11.2-17.7], respectively, all p<0.01) Overall plaque volumes were lowest with IMR and highest with FBP (121.7 [79.3-168.4], 138.7 [90.6-191.7], 147.0 [100.7-183.6]). Similarly, calcified volumes (>130 HU) were decreased with IMR as compared to HIR and FBP (105.9 [62.1-144.6], 110.2 [63.8-166.6], 115.9 [81.7-164.2], respectively, p<0.05 all). High-attenuation non-calcified volumes (90-129 HU) yielded similar values with FBP and HIR (p=0.81), however it was lower with IMR (p < 0.05 both). Intermediate- (30-89 HU) and low-attenuation (<30 HU) non-calcified volumes showed no significant difference (p=0.22 and p=0.67, respectively). CONCLUSIONS IMR improves image quality of coronary CTA and decreases calcified plaque volumes.

Right Ventricular Adaptation Is Associated with the Glu298Asp Variant of the NOS3 Gene in Elite Athletes

Nitric oxide (NO), an important endogenous pulmonary vasodilator is synthetized by the endothelial NO synthase (NOS3). Reduced NO bioavailability and thus the Glu298Asp polymorphism of NOS3 may enhance right ventricular (RV) afterload and hypertrophic remodeling and influence athletic performance. To test this hypothesis world class level athletes (water polo players, kayakers, canoeists, rowers, swimmers, n = 126) with a VO2 maximum greater than 50ml/kg/min were compared with non-athletic volunteers (n = 155). Cardiopulmonary exercise tests and cardiac magnetic resonance imaging (cMRI) were performed to determine structural or functional changes. Genotype distribution of the NOS3 Glu298Asp polymorphism was not affected by gender or physical performance. Cardiac MRI showed increased stroke volume with eccentric hypertrophy in all athletes regardless of their genotype. However, the Asp allelic variant carriers had increased RV mass index (32±6g versus 27±6g, p<0.01) and larger RV stroke volume index (71±10ml versus 64±10ml, p<0.01) than athletes with a Glu/Glu genotype. Genotype was not significantly associated with athletic performance. In the non-athletic group no genotype related differences were detected. The association between the NOS3 Glu298Asp polymorphism and RV structure and dimension in elite athletes emphasizes the importance of NOS3 gene function and NO bioavailability in sport related cardiac adaptation.

Radiomic Features Are Superior to Conventional Quantitative Computed Tomographic Metrics to Identify Coronary Plaques With Napkin-Ring SignCLINICAL PERSPECTIVE

Background— Napkin-ring sign (NRS) is an independent prognostic imaging marker of major adverse cardiac events. However, identification of NRS is challenging because of its qualitative nature. Radiomics is the process of extracting thousands of quantitative parameters from medical images to create big-data data sets that can identify distinct patterns in radiological images. Therefore, we sought to determine whether radiomic analysis improves the identification of NRS plaques. Methods and Results— From 2674 patients referred to coronary computed tomographic angiography caused by stable chest pain, expert readers identified 30 patients with NRS plaques and matched these with 30 non-NRS plaques with similar degree of calcification, luminal obstruction, localization, and imaging parameters. All plaques were segmented manually, and image data information was analyzed using Radiomics Image Analysis package for the presence of 8 conventional and 4440 radiomic parameters. We used the permutation test of symmetry to assess differences between NRS and non-NRS plaques, whereas we calculated receiver-operating characteristics’ area under the curve values to evaluate diagnostic accuracy. Bonferroni-corrected P<0.0012 was considered significant. None of the conventional quantitative parameters but 20.6% (916/4440) of radiomic features were significantly different between NRS and non-NRS plaques. Almost half of these (418/916) reached an area under the curve value >0.80. Short- and long-run low gray-level emphasis and surface ratio of high attenuation voxels to total surface had the highest area under the curve values (0.918; 0.894 and 0.890, respectively). Conclusions— A large number of radiomic features are different between NRS and non-NRS plaques and exhibit excellent discriminatory value.

Plaque imaging with CT—a comprehensive review on coronary CT angiography based risk assessment

CT based technologies have evolved considerably in recent years. Coronary CT angiography (CTA) provides robust assessment of coronary artery disease (CAD). Early coronary CTA imaging-as a gate-keeper of invasive angiography-has focused on the presence of obstructive stenosis. Coronary CTA is currently the only non-invasive imaging modality for the evaluation of non-obstructive CAD, which has been shown to contribute to adverse cardiac events. Importantly, improved spatial resolution of CT scanners and novel image reconstruction algorithms enable the quantification and characterization of atherosclerotic plaques. State-of-the-art CT imaging can therefore reliably assess the extent of CAD and differentiate between various plaque features. Recent studies have demonstrated the incremental prognostic value of adverse plaque features over luminal stenosis. Comprehensive coronary plaque assessment holds potential to significantly improve individual risk assessment incorporating adverse plaque characteristics, the extent and severity of atherosclerotic plaque burden. As a result, several coronary CTA based composite risk scores have been proposed recently to determine patients at high risk for adverse events. Coronary CTA became a promising modality for the evaluation of functional significance of coronary lesions using CT derived fractional flow reserve (FFR-CT) and/or rest/dynamic myocardial CT perfusion. This could lead to substantial reduction in unnecessary invasive catheterization procedures and provide information on ischemic burden of CAD. Discordance between the degree of stenosis and ischemia has been recognized in clinical landmark trials using invasive FFR. Both lesion stenosis and composition are possibly related to myocardial ischemia. The evaluation of lesion-specific ischemia using combined functional and morphological plaque information could ultimately improve the diagnostic performance of CTA and thus patient care. In this review we aimed to summarize current evidence on comprehensive coronary artery plaque assessment using coronary CTA.

Mellkasiaortastentgraft-beültetések Magyarországon 2012 és 2016 között

Thoracic aortic endograft implantation has become a widespread procedure in recent years, yet no report is available about Hungarian outcomes. Examination of our results is crucial to define further treatment strategies. Analysis of perioperative data from Hungarian thoracic endograft implantations based on the experience of 5 years is presented. Our retrospective, multicentric study analysed voluntarily reported data from all Hungarian institutions where thoracic endograft implantations are performed. Information was collected from every procedure performed in 5 years. Between 2012 and 2016, 131 thoracic stent graft implantations were performed in Hungary (67.18% male, mean age 62.80 years). 25.19% of the procedures were acute. 13.74% of the patients were diabetic. Indications for the procedure were aneurysm (64.89%), dissection (17.56%), aortic trauma (6.87%) and other conditions (10.69%). 73.91% of the dissection cases were acute. 16.47% of repaired aneurysms were ruptured. Additional preoperative revascularization (debranching) was performed in 26.72% of the cases. Postoperative stroke occured in 4.58%, temporary hemodialysis was needed in 1.53%, bowel ischaemia was present in 2.29% and reoperation within 30 days was needed in 5.34% of all cases. Thirty-day mortality of the procedure was 9.92%, 5-year long-term mortality reached 16.03%. Endovascular repair of the thoracic aorta is an effective procedure and our national data comfirmed its advantages compared to open thoracic surgery. Further use of the procedure in Hungary depends on the centralised care in vascular surgery and financial matters. Multidisciplinary cooperation and proper logistics are needed to provide patients with optimal treatment. Orv Hetil. 2018; 159(2): 53-57.Absztrakt: Napjainkban a vilagszerte elterjedt mellkasiaortastentgraft-beultetes hazankban is egyre nagyobb teret nyer. Eddig a hazai tapasztalatokrol atfogo beszamolo nem jelent meg. A modszer elterjedese folyamatban van, az eddigi eredmenyek elemzese a tovabbi kezelesi strategia optimalis meghatarozasa celjabol indokolt. A magyar mellkasi stentgraftműtetek perioperativ eredmenyeit elemeztuk 5 ev tapasztalatai alapjan. Retrospektiv, multicentrikus tanulmanyunk kereteben adatokat gyűjtottunk Magyarorszag minden mellkasi stentgraft-implantaciot vegző intezmenyeből. Az adatok jelentese onkentes volt, 5 ev mellkasi aortat erintő stentgraftbeultetesi adatait osszesitettuk. Magyarorszagon 2012 es 2016 kozott 131 mellkasiaortastentgraft-beultetest vegeztek. A ferfiak aranya 67,18%, a betegek atlageletkora 62,80 ev volt. Az elvegzett beavatkozas az esetek 25,19%-aban volt surgető. A betegek korelőzmenyeben 13,74%-ban szerepelt cukorbetegseg. A beavatkozast az esetek 64,89%-aban aneurysma, 17,56%-aban dissectio, ...

Genetically determined pattern of left ventricular function in normal and hypertensive hearts

We sought to assess the inheritance of left ventricular (LV) function using speckle‐tracking echocardiography and the impact of hypertension on modifying the genetically determined pattern of contraction in a population of twins. We recruited 92 Caucasian twin pairs, including 74 hypertensive (HTN) siblings. Beyond standard echocardiographic protocol, a speckle‐tracking analysis was performed, including global longitudinal strain (GLS). Systolic function, as assessed by ejection fraction, showed moderate heritability (61%); however, GLS showed higher and dominant heritability (75%). Heterogeneity models revealed that there were no differences between the HTN and non‐HTN subjects regarding the heritability of GLS. However, the heritability estimates of diastolic function parameters, including early diastolic strain rate, were low. LV systolic biomechanics is highly heritable. GLS shows dominant heritability, despite the presence of early‐stage hypertensive heart disease. Early diastolic parameters are rather determined by environmental factors. These findings suggest the presence of a genetic framework that conserves systolic function despite the expression of diastolic dysfunction and may underlie the phenotypic progression towards heart failure with preserved ejection fraction.