Publications by authors named "Valentin Sinitsyn"

31 Publications

Scintigraphy false-positive results for cardiac amyloidosis in a patient with Danon disease.

Clin Case Rep 2021 Aug 16;9(8):e04652. Epub 2021 Aug 16.

Sechenov University Moscow Russia.

Common diagnostic approach in patients with suspected cardiac amyloidosis includes cardiac magnetic resonance imaging and scintigraphy. We report the first clinical case of false-positive results of scintigraphy in a patient with Danon disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.4652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365861PMC
August 2021

Impact of COVID-19 on the imaging diagnosis of cardiac disease in Europe.

Open Heart 2021 08;8(2)

International Atomic Energy Agency, Vienna, Austria.

Objectives: We aimed to explore the impact of the COVID-19 pandemic on cardiac diagnostic testing and practice and to assess its impact in different regions in Europe.

Methods: The online survey organised by the International Atomic Energy Agency Division of Human Health collected information on changes in cardiac imaging procedural volumes between March 2019 and March/April 2020. Data were collected from 909 centres in 108 countries.

Results: Centres in Northern and Southern Europe were more likely to cancel all outpatient activities compared with Western and Eastern Europe. There was a greater reduction in total procedure volumes in Europe compared with the rest of the world in March 2020 (45% vs 41%, p=0.003), with a more marked reduction in Southern Europe (58%), but by April 2020 this was similar in Europe and the rest of the world (69% vs 63%, p=0.261). Regional variations were apparent between imaging modalities, but the largest reductions were in Southern Europe for nearly all modalities. In March 2020, location in Southern Europe was the only independent predictor of the reduction in procedure volume. However, in April 2020, lower gross domestic product and higher COVID-19 deaths were the only independent predictors.

Conclusion: The first wave of the COVID-19 pandemic had a significant impact on care of patients with cardiac disease, with substantial regional variations in Europe. This has potential long-term implications for patients and plans are required to enable the diagnosis of non-COVID-19 conditions during the ongoing pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2021-001681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349647PMC
August 2021

The Double Mutation -p.S363X and -p.D278X Is Associated with Left Ventricular Non-Compaction Cardiomyopathy: Case Report.

Int J Mol Sci 2021 Jun 24;22(13). Epub 2021 Jun 24.

National Research Center for Therapy and Preventive Medicine, Petroverigskiy Lane 10, 101990 Moscow, Russia.

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disease, with or without left ventricular dysfunction, which is characterized by a two-layer structure of the myocardium and an increased number of trabeculae. The study of familial forms of LVNC is helpful for risk prediction and genetic counseling of relatives. Here, we present a family consisting of three members with LVNC. Using a next-generation sequencing approach a combination of two (likely) pathogenic nonsense mutations -p.S363X and -p.D278X was identified in all three patients. encodes the cardiac T-box transcription factor 20. encodes desmoglein-2, which is part of the cardiac desmosomes and belongs to the cadherin family. Since the identified nonsense variant (-p.S363X) is localized in the extracellular domain of , we performed in vitro cell transfection experiments. These experiments revealed the absence of truncated at the plasma membrane, supporting the pathogenic relevance of -p.S363X. In conclusion, we suggest that in the future, these findings might be helpful for genetic screening and counseling of patients with LVNC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22136775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268202PMC
June 2021

Maximal Wall Thickness Measurement in Hypertrophic Cardiomyopathy: Biomarker Variability and its Impact on Clinical Care.

JACC Cardiovasc Imaging 2021 Nov 16;14(11):2123-2134. Epub 2021 Jun 16.

Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objectives: The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).

Background: Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).

Methods: A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.

Results: MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).

Conclusions: Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2021.03.032DOI Listing
November 2021

Impact of COVID-19 on Cardiovascular Testing in the United States Versus the Rest of the World.

JACC Cardiovasc Imaging 2021 09 16;14(9):1787-1799. Epub 2021 Jun 16.

Technion Israel Institute of Technology, Haifa, Israel.

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.

Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.

Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.

Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.

Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2021.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374310PMC
September 2021

Progression of Aortic Valve Calcification and Coronary Atherosclerosis: Similar but Not the Same.

Radiology 2021 07 11;300(1):87-88. Epub 2021 May 11.

From the Department of Radiology, University Hospital of Lomonosov, Moscow State University, Lomonosovsky prospect 27/10, Moscow, Russia 119991.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021210317DOI Listing
July 2021

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset.

Int J Mol Sci 2021 Apr 6;22(7). Epub 2021 Apr 6.

Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany.

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2-c.378+1G>T) in the first patient and a nonsense mutation (DSG2-p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22073786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038858PMC
April 2021

Noninvasive Assessment of the Fractional Flow Reserve with the CT FFRc 1D Method: Final Results of a Pilot Study.

Glob Heart 2021 01 4;16(1). Epub 2021 Jan 4.

Department of Cardiology, Functional and Ultrasound Diagnostics of N.V. Sklifosovsky Institute for Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, RU.

Background: Until recently, Russia did not utilize noninvasive fractional flow reserve (FFR) assessment. We developed an automated algorithm for noninvasive assessment of FFR based on a one-dimensional (1D) mathematical modeling.

Objective: The research aims to evaluate the diagnostic accuracy of this algorithm.

Methods: The study enrolled 80 patients: 16 of them underwent 64-slice computed tomography - included retrospectively, 64 - prospectively, with a 640-slice CT scan. Specialists processed CT images and evaluated noninvasive FFR. Ischemia was confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. The prospective group of patients was hospitalized for invasive FFR assessment as a reference standard. If ischemic, patients underwent stent implantation. In the retrospective group, patients already had invasive FFR values.Statistical analysis was performed using GraphPad Prism 8. We compared two methods using a Bland-Altman plot and per-vessel ROC curve analysis. Considering the abnormality of distribution by the Kolmogorov-Smirnov test, we have used Spearman's rank correlation coefficient.

Results: During data processing, three patients of the retrospective and 46 patients of the prospective group were excluded. The sensitivity of our method was 66.67% (95% CI: 46.71-82.03); the specificity was 78.95% (95% CI: 56.67-91.49), p = 0.0052, in the per-vessel analysis. In per-patient analysis, the sensitivity was 69.57% (95% CI: 49.13-84.40); the specificity was 87.50% (95% CI: 52.91-99.36), p = 0.0109. The area under the ROC curve in the per-vessel analysis was 77.52% (95% CI: 66.97-88.08), p < 0.0001.

Conclusion: The obtained indices of sensitivity, specificity, PPV, and NPV are, in general, comparable to those in other studies. Moreover, the noninvasive values of FFR yielded a high correlation coefficient with the invasive values. However, the AUC was not high enough, 77.52 (95% CI: 66.97-88.08), p < 0.0001. The discrepancy is probably attributed to the initial data heterogeneity and low statistical power.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5334/gh.837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792469PMC
January 2021

The Desmin () Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy.

Genes (Basel) 2021 01 19;12(1). Epub 2021 Jan 19.

National Medical Research Center for Therapy and Preventive Medicine, Petroverigsky per., 10, bld. 3, 101000 Moscow, Russia.

Here, we present a small Russian family, where the index patient received a diagnosis of left-ventricular non-compaction cardiomyopathy (LVNC) in combination with a skeletal myopathy. Clinical follow-up analysis revealed a LVNC phenotype also in her son. Therefore, we applied a broad next-generation sequencing gene panel approach for the identification of the underlying mutation. Interestingly, -p.A337P was identified in the genomes of both patients, whereas only the index patient carried -p.L1348X. encodes the muscle-specific intermediate filament protein desmin and encodes desmoplakin, which is a cytolinker protein connecting desmosomes with the intermediate filaments. Because the majority of mutations cause severe filament assembly defects and because this mutation was found in both affected patients, we analyzed this mutation in vitro by cell transfection experiments in combination with confocal microscopy. Of note, desmin-p.A337P forms cytoplasmic aggregates in transfected SW-13 cells and in cardiomyocytes derived from induced pluripotent stem cells underlining its pathogenicity. In conclusion, we suggest including the gene in the genetic analysis for LVNC patients in the future, especially if clinical involvement of the skeletal muscle is present.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12010121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835827PMC
January 2021

Preoperative CT-based detection of extrapancreatic perineural invasion in pancreatic cancer.

Sci Rep 2021 01 19;11(1):1800. Epub 2021 Jan 19.

Department of Oncology N4, City Clinical Cancer Hospital N1, Moscow, Russia.

Accuracy for computed tomography (CT) diagnosis of extrapancreatic perineural invasion (EPNI) in pancreatic ductal adenocarcinoma (PDAC), which is a significant cause of recurrence, has not been established. The aim of the study was to evaluate the diagnostic accuracy of CT in detecting EPNI preoperatively in resectable PDAC of the pancreatic head. Retrospective study design was approved by institutional review board. Preoperative CT-series of 46 patients with resectable PDAC were evaluated by two independent observers. Plexus Pancreaticus Capitalis-II (PPC-II) was assessed as this area is more susceptible for EPNI. All patients underwent surgery with dedicated histopathology, which served as the reference standard. Histologically EPNI was confirmed in 63.1%. Sensitivity of MDCT was 93.1% (95% confidence interval (CI) 77.23% to 99.15%), specificity 64.7% (95% CI 38.33% to 85.79%) with area under the curve (AUC) 0.789 for the first observer. Positive predictive value (PPV) was 81.82% (95% CI 70.12% to 89.62%), negative predictive value (NPV-84.62% (95% CI 57.98% to 95.64%) with diagnostic accuracy of 82.61% (95% CI 68.58% to 92.18%). Interobserver agreement showed k-value of 0.893 ([Formula: see text]), which represents very good agreement between observers. Median actual survival in patients without EPNI was 30 months (95% CI 18.284-41.716), in patients with EPNI-13 months (95% CI 12.115-13.885). CT provides sufficient diagnostic information to detect PPC-II invasion in patients with resectable PDAC of the pancreatic head. Preoperative detection of EPNI might be an additional argument to perform neoadjuvant chemotherapy in patients with resectable PDAC. It should be included in preoperative evaluation form of CT-findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-81322-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815796PMC
January 2021

International Impact of COVID-19 on the Diagnosis of Heart Disease.

J Am Coll Cardiol 2021 01;77(2):173-185

International Atomic Energy Agency, Vienna, Austria.

Background: The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.

Objectives: The study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices.

Methods: The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.

Results: Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth.

Conclusions: COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.10.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836433PMC
January 2021

Variations in CT Utilization, Protocols, and Radiation Doses in COVID-19 Pneumonia: Results from 28 Countries in the IAEA Study.

Radiology 2021 03 10;298(3):E141-E151. Epub 2020 Nov 10.

From the Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 75 Blossom Ct, Room 248, Boston, MA 02114 (F.H., M.K.K.); Radiation Protection of Patients Unit, International Atomic Energy Agency, Vienna, Austria (O.H., J.V.); The Royal Hospital, Muscat, Oman (R.A.U.); Alfa Scan Radiology Center, Cairo, Egypt (S.A.); Department of Radiology, Lithuanian University of Health Sciences, Kaunas, Lithuania (A.B.); Institute of Physics, University of São Paulo, São Paulo, Brazil (P.R.C.); Hamad Medical Corporation, Doha, Qatar (A.D.); Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, Skopje, North Macedonia (V.G.); Tartu University Hospital, University of Tartu, Institute of Clinical Medicine, Department of Radiology, Tartu, Estonia (P.I.); Aleksandrovska University Hospital, Sofia, Bulgaria (D.K.L.); Institute of Radioprotection and Dosimetry, National Nuclear Energy Commission, Rio de Janeiro, Brazil (S.K.R.); Radiology Department, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran (I.M.); Medical Physics Unit, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy (O.R.); Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova (N.R.); Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, Accra, Ghana (I.S.); University Hospital, Lomonosov Moscow State University, Moscow, Russian Federation (V.S.); University Hospital Osijek, Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia (T.T.); and Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France (C.V.N.T.).

Background There is lack of guidance on specific CT protocols for imaging patients with coronavirus disease 2019 (COVID-19) pneumonia. Purpose To assess international variations in CT utilization, protocols, and radiation doses in patients with COVID-19 pneumonia. Materials and Methods In this retrospective data collection study, the International Atomic Energy Agency coordinated a survey between May and July 2020 regarding CT utilization, protocols, and radiation doses from 62 health care sites in 34 countries across five continents for CT examinations performed in patients with COVID-19 pneumonia. The questionnaire obtained information on local prevalence, method of diagnosis, most frequent imaging, indications for CT, and specific policies on use of CT in COVID-19 pneumonia. Collected data included general information (patient age, weight, clinical indication), CT equipment (CT make and model, year of installation, number of detector rows), scan protocols (body region, scan phases, tube current and potential), and radiation dose descriptors (CT dose index and dose length product). Descriptive statistics and generalized estimating equations were performed. Results Data from 782 patients (median age, 59 years [interquartile range, 15 years]) from 54 health care sites in 28 countries were evaluated. Less than one-half of the health care sites used CT for initial diagnosis of COVID-19 pneumonia and three-fourths used CT for assessing disease severity. CT dose index varied based on CT vendors (7-11 mGy; < .001), number of detector rows (8-9 mGy; < .001), year of CT installation (7-10 mGy; = .006), and reconstruction techniques (7-10 mGy; = .03). Multiphase chest CT examinations performed at 20% of sites (11 of 54) were associated with higher dose length product compared with single-phase chest CT examinations performed in 80% of sites (43 of 54) ( = .008). Conclusion CT use, scan protocols, and radiation doses in patients with coronavirus disease 2019 pneumonia showed wide variation across health care sites within the same and between different countries. Many patients were imaged multiple times and/or with multiphase CT scan protocols. © RSNA, 2021 See also the editorial by Lee in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2020203453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673104PMC
March 2021

Neural Correlates of Group Versus Individual Problem Solving Revealed by fMRI.

Front Hum Neurosci 2020 28;14:290. Epub 2020 Aug 28.

Research Institute of Neuropsychology of Speech and Writing, Moscow, Russia.

Group problem solving is a prototypical complex collective intellectual activity. Psychological research provides compelling evidence that problem solving in groups is both qualitatively and quantitatively different from doing so alone. However, the question of whether individual and collective problem solving involve the same neural substrate has not yet been addressed, mainly due to methodological limitations. In the current study, functional magnetic resonance imaging was performed to compare brain activation when participants solved Raven-like matrix problems in a small group and individually. In the group condition, the participant in the scanner was able to discuss the problem with other team members using a special communication device. In the individual condition, the participant was required to think aloud while solving the problem in the silent presence of the other team members. Greater activation was found in several brain regions during group problem solving, including the medial prefrontal cortex; lateral parietal, cingulate, precuneus and retrosplenial cortices; frontal and temporal poles. These areas have been identified as potential components of the so-called "social brain" on the basis of research using offline judgments of material related to socializing. Therefore, this study demonstrated the actual involvement of these regions in real-time social interactions, such as group problem solving. However, further connectivity analysis revealed that the social brain components are co-activated, but do not increase their coupling during cooperation as would be suggested for a holistic network. We suggest that the social mode of the brain may be described instead as a re-configuration of connectivity between basic networks, and we found decreased connectivity between the language and salience networks in the group compared to the individual condition. A control experiment showed that the findings from the main experiment cannot be entirely accounted for by discourse comprehension. Thus, the study demonstrates affordances provided by the presented new technique for neuroimaging the "group mind," implementing the single-brain version of the second-person neuroscience approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2020.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483667PMC
August 2020

Macro- and microstructural changes in cosmonauts' brains after long-duration spaceflight.

Sci Adv 2020 Sep 4;6(36). Epub 2020 Sep 4.

imec-Vision Lab, Department of Physics, University of Antwerp, Antwerp, Belgium.

Long-duration spaceflight causes widespread physiological changes, although its effect on brain structure remains poorly understood. In this work, we acquired diffusion magnetic resonance imaging to investigate alterations of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) compositions in each voxel, before, shortly after, and 7 months after long-duration spaceflight. We found increased WM in the cerebellum after spaceflight, providing the first clear evidence of sensorimotor neuroplasticity. At the region of interest level, this increase persisted 7 months after return to Earth. We also observe a widespread redistribution of CSF, with concomitant changes in the voxel fractions of adjacent GM. We show that these GM changes are the result of morphological changes rather than net tissue loss, which remained unclear from previous studies. Our study provides evidence of spaceflight-induced neuroplasticity to adapt motor strategies in space and evidence of fluid shift-induced mechanical changes in the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aaz9488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473746PMC
September 2020

Modulation of Intrinsic Brain Connectivity by Implicit Electroencephalographic Neurofeedback.

Front Hum Neurosci 2020 23;14:192. Epub 2020 Jun 23.

Laboratory for Cognitive Research, National Research University Higher School of Economics, Moscow, Russia.

Despite the increasing popularity of neurofeedback, its mechanisms of action are still poorly understood. This study aims to describe the processes underlying implicit electroencephalographic neurofeedback. Fifty-two healthy volunteers were randomly assigned to a single session of infra-low frequency neurofeedback or sham neurofeedback, with electrodes over the right middle temporal gyrus and the right inferior parietal lobule. They observed a moving rocket, the speed of which was modulated by the waveform derived from a band-limited infra-low frequency filter. Immediately before and after the session, the participants underwent a resting-state fMRI. Network-based statistical analysis was applied, comparing post- vs. pre-session and real vs. sham neurofeedback conditions. As a result, two phenomena were observed. First, we described a brain circuit related to the implicit neurofeedback process itself, consisting of the lateral occipital cortex, right dorsolateral prefrontal cortex, left orbitofrontal cortex, right ventral striatum, and bilateral dorsal striatum. Second, we found increased connectivity between key regions of the salience, language, and visual networks, which is indicative of integration in sensory processing. Thus, it appears that a single session of implicit infra-low frequency electroencephalographic neurofeedback leads to significant changes in intrinsic brain connectivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2020.00192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324903PMC
June 2020

T mapping performance and measurement repeatability: results from the multi-national T mapping standardization phantom program (T1MES).

J Cardiovasc Magn Reson 2020 05 7;22(1):31. Epub 2020 May 7.

The Prince Charles Hospital, Griffith University and University of Queensland, Brisbane, Australia.

Background: The T Mapping and Extracellular volume (ECV) Standardization (T1MES) program explored T mapping quality assurance using a purpose-developed phantom with Food and Drug Administration (FDA) and Conformité Européenne (CE) regulatory clearance. We report T measurement repeatability across centers describing sequence, magnet, and vendor performance.

Methods: Phantoms batch-manufactured in August 2015 underwent 2 years of structural imaging, B and B, and "reference" slow T testing. Temperature dependency was evaluated by the United States National Institute of Standards and Technology and by the German Physikalisch-Technische Bundesanstalt. Center-specific T mapping repeatability (maximum one scan per week to minimum one per quarter year) was assessed over mean 358 (maximum 1161) days on 34 1.5 T and 22 3 T magnets using multiple T mapping sequences. Image and temperature data were analyzed semi-automatically. Repeatability of serial T was evaluated in terms of coefficient of variation (CoV), and linear mixed models were constructed to study the interplay of some of the known sources of T variation.

Results: Over 2 years, phantom gel integrity remained intact (no rips/tears), B and B homogenous, and "reference" T stable compared to baseline (% change at 1.5 T, 1.95 ± 1.39%; 3 T, 2.22 ± 1.44%). Per degrees Celsius, 1.5 T, T (MOLLI 5s(3s)3s) increased by 11.4 ms in long native blood tubes and decreased by 1.2 ms in short post-contrast myocardium tubes. Agreement of estimated T times with "reference" T was similar across Siemens and Philips CMR systems at both field strengths (adjusted R ranges for both field strengths, 0.99-1.00). Over 1 year, many 1.5 T and 3 T sequences/magnets were repeatable with mean CoVs < 1 and 2% respectively. Repeatability was narrower for 1.5 T over 3 T. Within T1MES repeatability for native T was narrow for several sequences, for example, at 1.5 T, Siemens MOLLI 5s(3s)3s prototype number 448B (mean CoV = 0.27%) and Philips modified Look-Locker inversion recovery (MOLLI) 3s(3s)5s (CoV 0.54%), and at 3 T, Philips MOLLI 3b(3s)5b (CoV 0.33%) and Siemens shortened MOLLI (ShMOLLI) prototype 780C (CoV 0.69%). After adjusting for temperature and field strength, it was found that the T mapping sequence and scanner software version (both P < 0.001 at 1.5 T and 3 T), and to a lesser extent the scanner model (P = 0.011, 1.5 T only), had the greatest influence on T across multiple centers.

Conclusion: The T1MES CE/FDA approved phantom is a robust quality assurance device. In a multi-center setting, T mapping had performance differences between field strengths, sequences, scanner software versions, and manufacturers. However, several specific combinations of field strength, sequence, and scanner are highly repeatable, and thus, have potential to provide standardized assessment of T times for clinical use, although temperature correction is required for native T tubes at least.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-020-00613-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204222PMC
May 2020

Context-dependency in the Cognitive Bias Task and Resting-state Functional Connectivity of the Dorsolateral Prefrontal Cortex.

J Int Neuropsychol Soc 2020 09 28;26(8):749-762. Epub 2020 Apr 28.

Department of Psychiatry, University of North Carolina, Chapel Hill, the USA.

Objective: Goldberg, the author of the "novelty-routinization" framework, suggested a new pair of cognitive styles for agent-centered decision-making (DM), context-dependency/independency (CD/CI), quantified by the Cognitive Bias Task (CBT) and supposedly reflecting functional brain hemispheric specialization. To date, there are only three lesion and activation neuroimaging studies on the CBT with the largest sample of 12 participants. The present study is the first to analyze whole-brain functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC), involved in contextual agent-centered DM.

Method: We compared whole-brain resting-state FC of the DLPFC between CD (n = 24) and CI (n = 22) healthy participants. Additionally, we investigated associations between CD/CI and different aspects of executive functions.

Results: CD participants had stronger positive FC of the DLPFC with motor and visual regions; FC of the left DLPFC was more extensive. CI participants had stronger positive FC of the left DLPFC with right prefrontal and parietal-occipital areas and of the left and right DLPFC with ipsilateral cerebellar hemispheres. No sex differences were found. CD/CI had nonlinear associations with working memory.

Conclusions: The findings suggest that CD and CI are associated with different patterns of DLPFC FC. While CD is associated with FC between DLPFC and areas presumably involved in storing representations of current situation, CI is more likely to be associated with FC between DLPFC and right-lateralized associative regions, probably involved in the inhibition of the CD response and switching from processing of incoming perceptual information to creation of original response strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1355617720000302DOI Listing
September 2020

Functional connectivity of the dorsolateral prefrontal cortex contributes to different components of executive functions.

Int J Psychophysiol 2020 05 25;151:70-79. Epub 2020 Feb 25.

National Research University Higher School of Economics, Moscow, Russia.

Objective: The dorsolateral prefrontal cortex (DLPFC) orchestrates other brain regions and plays a vital role for "the most uniquely human" executive functions (EFs), which are divided into distinct components. Components of EFs have been localized to different brain regions and at the same time the DLPFC was found to be involved in a majority of EF components. The possible mechanism of the DLPFC's contribution to EF components might be found in DLPFC functional connectivity (FC): this FC of the DLPFC with other brain regions contributes to different EF components.

Method: To explore the DLPFC FC contribution to different EFs, we used an integrative approach involving analysis of fMRI and neuropsychological assessment of EFs. Fifty healthy adults (27 females and 23 males, mean age 34.5 ± 16.6 years) underwent neuropsychological assessment of EFs as well as task-based and resting-state fMRI. Task-based fMRI was applied as a functional localizer for individually defined DLPFC ROIs that were further used for the FC seed-based correlation analysis of the resting-state data. Then we looked for associations between individual scores of different EF components and the whole-brain resting-state FC of the DLPFC.

Results: Resting-state correlates of DLPFC FC were revealed for three out of the seven EF components derived from an extensive neuropsychological assessment: inhibition, switching, and the verbal EF component.

Conclusions: Our study is the first to reveal the contribution of the DLPFC FC to several distinct EF components. The obtained results give insight into the brain mechanisms of EFs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpsycho.2020.02.013DOI Listing
May 2020

Alterations of Functional Brain Connectivity After Long-Duration Spaceflight as Revealed by fMRI.

Front Physiol 2019 4;10:761. Epub 2019 Jul 4.

Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.

The present study reports alterations of task-based functional brain connectivity in a group of 11 cosmonauts after a long-duration spaceflight, compared to a healthy control group not involved in the space program. To elicit the postural and locomotor sensorimotor mechanisms that are usually most significantly impaired when space travelers return to Earth, a plantar stimulation paradigm was used in a block design fMRI study. The motor control system activated by the plantar stimulation involved the pre-central and post-central gyri, SMA, SII/operculum, and, to a lesser degree, the insular cortex and cerebellum. While no post-flight alterations were observed in terms of activation, the network-based statistics approach revealed task-specific functional connectivity modifications within a broader set of regions involving the activation sites along with other parts of the sensorimotor neural network and the visual, proprioceptive, and vestibular systems. The most notable findings included a post-flight increase in the stimulation-specific connectivity of the right posterior supramarginal gyrus with the rest of the brain; a strengthening of connections between the left and right insulae; decreased connectivity of the vestibular nuclei, right inferior parietal cortex (BA40) and cerebellum with areas associated with motor, visual, vestibular, and proprioception functions; and decreased coupling of the cerebellum with the visual cortex and the right inferior parietal cortex. The severity of space motion sickness symptoms was found to correlate with a post- to pre-flight difference in connectivity between the right supramarginal gyrus and the left anterior insula. Due to the complex nature and rapid dynamics of adaptation to gravity alterations, the post-flight findings might be attributed to both the long-term microgravity exposure and to the readaptation to Earth's gravity that took place between the landing and post-flight MRI session. Nevertheless, the results have implications for the multisensory reweighting and gravitational motor system theories, generating hypotheses to be tested in future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.00761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621543PMC
July 2019

Analysis and Interpretation of Perfusion CT in Oncology: Type of Cancer Matters.

Radiology 2019 Sep 9;292(3):636-637. Epub 2019 Jul 9.

From the Department of Radiology, Medical Faculty of Lomonosov, Moscow State University, Lomonosovsky prospect 27/1, Moscow 119991, Russia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2019191265DOI Listing
September 2019

Brain ventricular volume changes induced by long-duration spaceflight.

Proc Natl Acad Sci U S A 2019 05 6;116(21):10531-10536. Epub 2019 May 6.

Lab for Equilibrium Investigations and Aerospace, University of Antwerp, 2610 Antwerp, Belgium.

Long-duration spaceflight induces detrimental changes in human physiology. Its residual effects and mechanisms remain unclear. We prospectively investigated the changes in cerebrospinal fluid (CSF) volume of the brain ventricular regions in space crew by means of a region of interest analysis on structural brain scans. Cosmonaut MRI data were investigated preflight ( = 11), postflight ( = 11), and at long-term follow-up 7 mo after landing ( = 7). Post hoc analyses revealed a significant difference between preflight and postflight values for all supratentorial ventricular structures, i.e., lateral ventricle (mean % change ± SE = 13.3 ± 1.9), third ventricle (mean % change ± SE = 10.4 ± 1.1), and the total ventricular volume (mean % change ± SE = 11.6 ± 1.5) (all < 0.0001), with higher volumes at postflight. At follow-up, these structures did not quite reach baseline levels, with still residual increases in volume for the lateral ventricle (mean % change ± SE = 7.7 ± 1.6; = 0.0009), the third ventricle (mean % change ± SE = 4.7 ± 1.3; = 0.0063), and the total ventricular volume (mean % change ± SE = 6.4 ± 1.3; = 0.0008). This spatiotemporal pattern of CSF compartment enlargement and recovery points to a reduced CSF resorption in microgravity as the underlying cause. Our results warrant more detailed and longer longitudinal follow-up. The clinical impact of our findings on the long-term cosmonauts' health and their relation to ocular changes reported in space travelers requires further prospective studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1820354116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535034PMC
May 2019

Noncompaction cardiomyopathy is caused by a novel in-frame desmin (DES) deletion mutation within the 1A coiled-coil rod segment leading to a severe filament assembly defect.

Hum Mutat 2019 06 3;40(6):734-741. Epub 2019 Apr 3.

Laboratory of Functional Genomics, Research Centre for Medical Genetics (RCMG), Moscow, Russia, Russia.

Mutations in DES, encoding desmin protein, are associated with different kinds of skeletal and/or cardiac myopathies. However, it is unknown, whether DES mutations are associated with left ventricular hypertrabeculation (LVHT). Here, we performed a clinical examination and subsequent genetic analysis in a family, with two individuals presenting LVHT with conduction disease and skeletal myopathy. The genetic analysis revealed a novel small in-frame deletion within the DES gene, p.Q113_L115del, affecting the α-helical rod domain. Immunohistochemistry analysis of explanted myocardial tissue from the index patient revealed an abnormal cytoplasmic accumulation of desmin and a degraded sarcomeric structure. Cell transfection experiments with wild-type and mutant desmin verified the cytoplasmic aggregation and accumulation of mutant desmin. Cotransfection experiments were performed to model the heterozygous state of the patients and revealed a dominant negative effect of the mutant desmin on filament assembly. DES:p.Q113_L115del is classified as a pathogenic mutation associated with dilated cardiomyopathy with prominent LVHT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23747DOI Listing
June 2019

Cardiac Dual-Energy CT with Late Iodine Enhancement as an Alternative to Late Gadolinium Enhancement MRI.

Radiology 2018 09 10;288(3):692-693. Epub 2018 Jul 10.

From the Department of Radiology, Medical Faculty of Lomonosov Moscow State University, Lomonosovsky Prospect 27/1, Moscow 119991, Russia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2018181059DOI Listing
September 2018

Calcification of coronary arteries in early rheumatoid arthritis prior to anti-rheumatic therapy.

Rheumatol Int 2018 Feb 27;38(2):211-217. Epub 2017 Oct 27.

Department of Systemic Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation.

Accelerated coronary atherosclerosis is common in patients with rheumatoid arthritis (RA). To examine coronary artery calcification (CAC) frequency and severity, its correlation with traditional risk factors (TRF) of cardiovascular diseases (CVD) and inflammatory markers in patients with early RA prior to anti-rheumatic therapy. RA adult patients (ACR/EULAR criteria, 2010, duration ≤ 12 months, without prior administration of disease-modifying anti-rheumatic drugs, glucocorticoids) underwent 32-row scanning for CAC scoring. Agatston, volume and mass calcium scores were calculated. Additionally, we used calculators on the website of the Multi-Ethnic Study of Atherosclerosis. 74 RA patients (women n = 54 (73%), median age 56 years, median RA duration 6 months) with moderate/high RA activity (median DAS28 [ESR] 5.4) were enrolled within the framework of the observational study. Most of the patients had multiple TRFs of CVD and subclinical organ damage. CAC has been detected in 34 (46%) early RA patients. Calcification severity was significantly higher in men and in patients with ischemic heart disease (IHD). In patients younger than 45 years (n = 16) CAC was not detected. Among patients older than 45 years (n = 58), the frequency of CAC was 59%: asymptomatic patients-n = 46 (48%), IHD patients-n = 12 (100%). Among asymptomatic patients the presence of CAC associated with a significantly higher frequency of arterial hypertension (1.6 fold) compared with cases without CAC. Coronary age in asymptomatic patients with CAC and IHD patients was significantly greater than their actual age. More than half of early RA patients older 45 years had CAC. The presence and severity of CAC correlated positively with TRFs, but not with lipid levels and RA activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00296-017-3860-9DOI Listing
February 2018

Cortical reorganization in an astronaut's brain after long-duration spaceflight.

Brain Struct Funct 2016 06 12;221(5):2873-6. Epub 2015 May 12.

Antwerp University Research Centre for Equilibrium and Aerospace (AUREA), Antwerp University Hospital and University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.

To date, hampered physiological function after exposure to microgravity has been primarily attributed to deprived peripheral neuro-sensory systems. For the first time, this study elucidates alterations in human brain function after long-duration spaceflight. More specifically, we found significant differences in resting-state functional connectivity between motor cortex and cerebellum, as well as changes within the default mode network. In addition, the cosmonaut showed changes in the supplementary motor areas during a motor imagery task. These results highlight the underlying neural basis for the observed physiological deconditioning due to spaceflight and are relevant for future interplanetary missions and vestibular patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00429-015-1054-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884200PMC
June 2016

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts.

BMJ 2012 Jun 12;344:e3485. Epub 2012 Jun 12.

Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, Netherlands.

Objectives: To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations.

Design: Retrospective pooled analysis of individual patient data.

Setting: 18 hospitals in Europe and the United States.

Participants: Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively).

Main Outcome Measures: Obstructive coronary artery disease (≥ 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined.

Results: We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory.

Conclusions: Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.e3485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374026PMC
June 2012

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension.

Eur Heart J 2011 Jun 2;32(11):1316-30. Epub 2011 Mar 2.

Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

Aims: The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort.

Methods And Results: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence.

Conclusion: Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehr014DOI Listing
June 2011

Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: a multicenter, randomized, double-blind trial.

Circulation 2006 Jan 16;113(3):427-37. Epub 2006 Jan 16.

Department of Cardiology, University Clinic Essen, Essen, Germany.

Background: Recent clinical trials have suggested that intensive versus standard lipid-lowering therapy provides for additional benefit. Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification (CAC) in serial measurements.

Methods And Results: In a multicenter, randomized, double-blind trial, 471 patients (age 61+/-8 years) who had no history of coronary artery disease and no evidence of high-grade coronary stenoses (>50% diameter reduction) were randomized if they had > or =2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidenced by a CAC score > or =30. Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months. Progression of CAC volume scores could be analyzed in 366 patients. After pretreatment with 10 mg of atorvastatin for 4 weeks, 12 months of study medication reduced LDL cholesterol from 106+/-22 to 87+/-33 mg/dL in the group randomized to receive 80 mg of atorvastatin (P<0.001), whereas levels remained stable in the group randomized to receive 10 mg (108+/-23 at baseline, 109+/-28 mg/dL at the end of the study, P=NS). The mean progression of CAC volume scores, corrected for the baseline CAC volume score, was 27% (95% CI 20.8% to 33.1%) in the 80-mg atorvastatin group and 25% (95% CI 19.1% to 30.8%) in the 10-mg atorvastatin group (P=0.65). CAC progression showed no relationship with on-treatment LDL cholesterol levels.

Conclusions: We did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis. Over a period of 12 months, intensive atorvastatin therapy was unable to attenuate CAC progression compared with standard atorvastatin therapy. The possibility remains that the time window was too short to demonstrate an effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.105.568147DOI Listing
January 2006
-->