Publications

Objectives This study sought to analyze the natural history of coronary atherosclerosis by multislice computed tomography (MSCT) and assess the serial changes in coronary plaque burden, lumen dimensions, and arterial remodeling. Background MSCT can comprehensively assess coronary atherosclerosis by combining lumen and plaque size parameters. Methods Thirty-two patients with acute coronary syndromes underwent 64-slice computed tomography angiography after percutaneous coronary intervention at baseline and after a median of 39 months. All patients received contemporary medical treatment. All available coronary segments in every subject were analyzed. The progression of atherosclerosis per segment and per patient was assessed by means of change in percent atheroma volume (PAV), change in normalized total atheroma volume (TAVnorm), and percent change in TAV (% change in TAV). Serial coronary remodeling was also assessed. Measures of lumen stenosis included percent diameter stenosis (%DS), minimum lumen diameter (MLD), percent area stenosis (%AS), and minimum lumen area (MLA). For each patient, the mean of all matched segments was calculated at the 2 time points. Clinical events at follow-up were documented. Results The PAV did not change significantly (−0.15 ± 3.64%, p = 0.72). The mean change in TAVnorm was 47.36 ± 143.24 mm3 (p = 0.071), and the % change in TAV was 6.7% (p = 0.029). The MLD and MLA increased by 0.15 mm (−0.09 to 0.24, p = 0.039) and 0.52 mm2 (−0.38 to 1.04, p = 0.034) respectively, which was accompanied by vessel enlargement, with 53% of the patients showing expansive positive remodeling. Patients with clinical events had a larger TAVnorm at baseline (969.72 mm3 vs. 810.77 mm3, p = 0.010). Conclusions MSCT can assess the progression of coronary atherosclerosis and may be used for noninvasive monitoring of pharmacological interventions in coronary artery disease. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466)

Objectives This study sought to investigate whether the anatomical location of the disease carries prognostic implications in patients undergoing drug-eluting stent (DES) implantation for the left main coronary artery (LMCA) stenosis. Background Liberal use of DES, compared with a bare metal stent (BMS), has resulted in an improved outcome in patients undergoing LMCA intervention. However, the overall event rate in this subset of patients remains high, and alternative tools to risk-stratify this population beyond conventional surgical risk status would be desirable. Methods From April 2002 to June 2004, 130 patients received DES as part of the percutaneous intervention for LMCA stenoses in our institution. Distal LMCA disease (DLMD) was present in 94 patients. They were at higher surgical risk and presented with a greater coronary disease extent compared with patients without DLMD. Results After a median of 587 days (range 368 to 1,179 days), the cumulative incidence of major adverse cardiac events (MACE) was significantly higher in patients with DLMD at 30% versus 11% in those without DLMD (hazard ratio [HR] 3.42, 95% confidence interval [CI] 1.34 to 9.7; p = 0.007), mainly driven by the different rate of target vessel revascularization (13% and 3%; HR 6, 95% CI 1.2 to 29; p = 0.02). After adjustment for confounders, DLMD (HR 2.79,95% CI 1.17 to 8.9; p = 0.032) and surgical risk status (HR 2.18,95% CI 1.06 to 4.5; p = 0.038) remained independent and complementary predictors of MACE. Conclusions Distal LMCA disease carries independent prognostic implications, and it may help in selecting the most appropriate patient subset for LMCA intervention beyond the conventional surgical risk status in the DES era.

The predilection sites of atherosclerotic plaques implicate rheologic factors like shear stress underlying the genesis of atherosclerosis. Presently no technique is available that enables one to provide 3D shear stress data in human coronary arteries in vivo. In this study, we describe a novel technique that uses a recently developed 3D reconstruction technique to calculate shear stress on the endothelium with computational fluid dynamics. In addition, we calculated local wall thickness, the principal plane of curvature, and the location of plaque with reference to this plane, relating these results to shear stress in a human right coronary artery in vivo. Wall thickness and shear stress values for the entire vessel for three inflow-velocity values (10 cm/second, 20 cm/second, and 30 cm/second equivalents with the Reynolds numbers 114, 229, and 457) were as follows: 0.65±0.37 mm (n=1600) and 19.6±1.7 dyne/cm 2 ; 46.1±8.1 dyne/cm 2 and 80.1±16.8 dyne/cm 2 (n=1600). Curvature was 25±9 (m −1 ), resulting in Dean numbers 20±8; 46±16, and 93±33. Selection of data at the inner curvature of the right coronary artery provided wall thickness values of 0.90±0.41 mm (n=100), and shear stress was 17±17, 38±44, and 77±54 dyne/cm 2 (n=100), whereas wall thickness values at the outer curve were 0.37±0.17 mm (n=100) and shear stress values were 22±17, 60±44, and 107±79 dyne/cm 2 (n=100). These findings could be reconciled by an inverse relationship between wall thickness and shear stress for each velocity level under study. For the first time for human vessels in vivo, evidence is presented that low shear stress promotes atherosclerosis. As the method is nondestructive, it allows repeated measurements in the same patient and will provide new insights in the progress of atherosclerosis.

No abstract is provided for this article.

<b>Background:</b> COVID-19 disease primarily affects the respiratory system but can evolve to a multisystem inflammatory syndrome. Increased mortality is observed in elderly and in patients with age-related comorbidities. Cellular senescence is characterised by cell-cycle arrest and a proinflammatory 'Senescence-Associated-Secretory-Phenotype' (SASP). Viral infection has been associated with senescence. We have studied whether SARS-CoV-2 may be associated with senescence and the SASP phenotype. <b>Methods:</b> Lung tissues from ten COVID-19 and ten age-matched control patients were analysed by immunohistochemistry for: SARS-CoV-2, ACE-2, TTF-1, CD68, p16^INK4, IL-1β, IL-6 and the novel cellular senescence marker SenTraGor. <b>Results:</b> SARS-CoV-2 was detected in alveolar type-II (AT2) pneumocytes of all COVID-19 patients using a monoclonal antibody we developed against the spike protein. Electron microscopy confirmed the presence of the virus within AT2 cells. We observed that a proportion of SARS-CoV-2 AT2 infected cells exerted features of senescence, displaying strong reactivity to SenTraGor. Senescent phenotype was further confirmed with p16^INK4&nbsp;co-staining. Subsequently, we found that SenTraGor-positive cells in COVID-19 samples co-expressed IL-1β and IL-6, which were absent in non-COVID-19 cases. <b>Conclusion:</b> This is the first evidence of senescence and expression of SASP components in SARS-CoV-2 infected human lung cells. Further studies need to determine whether senescence pre-exists at the time of infection, making cells susceptible to the virus, or is triggered as an antiviral response. Our findings justify the application of senotherapeutics for treatment or prevention of COVID-19 patients.

Journal Article Contrast echocardiographic shunts may persist after atrial septal defect repair Get access T. SANTOSO, T. SANTOSO Thoraxcenter, Erasmus University and University HospitalRotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar R. S. MELTZER, R. S. MELTZER Thoraxcenter, Erasmus University and University HospitalRotterdam, The Netherlands Requests for reprints to: Dr R. Meltzer, Cardiology Division, Mount Sinai Medical Center, 1 Gustave Levy Place, New York, N.Y. 10029, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar S. CASTELLANOS, S. CASTELLANOS Thoraxcenter, Erasmus University and University HospitalRotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar P. W. SERRUYS, P. W. SERRUYS Thoraxcenter, Erasmus University and University HospitalRotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar J. ROELANDT J. ROELANDT Thoraxcenter, Erasmus University and University HospitalRotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 4, Issue 2, February 1983, Pages 129–136, https://doi.org/10.1093/oxfordjournals.eurheartj.a061427 Published: 01 February 1983 Article history Received: 10 December 1981 Revision received: 26 April 1982 Published: 01 February 1983

OBJECTIVE--To investigate whether balloon dilatation of the aortic valve induces long-term macroscopic or histological changes or both to explain the restenosis process. DESIGN--Prospective study of 39 consecutive patients. Sixteen later (mean (SD) 12 (10) months) required operation. This non-randomised subgroup was compared with 10 patients who had aortic valve replacement without prior dilatation. SETTING--University cardiology and cardiac surgery centre and pathology department. PATIENTS--16 patients who had aortic valve replacement because of failure of or restenosis after balloon dilatation of the aortic valve. Twelve resected valves were examined. INTERVENTIONS--Percutaneous balloon dilatation of the aortic valve (maximal balloon size: trefoil 3 x 12 mm balloon or bifoil 2 x 19 mm balloon) and surgical inspection before excision of the aortic valve leaflets during open-chest aortic valve replacement. Fixation, decalcification, and staining for histology. MAIN OUTCOME MEASURES--Presence of long-term pathological changes in the resected valve and their relation to restenosis after balloon dilatation. RESULTS--Macroscopically the previously dilated valves were indistinguishable from valves from the patients who had valve replacement only. Microscopically, the dilated aortic valves showed areas of young scar tissue that were not seen in a control group of surgically excised stenotic aortic valves. This persistent scarring reaction was seen around small tears or lacerations of the collagenous valve stroma, fractures in calcified areas, and splits in commissures. Young scar tissue without collagenisation was still present 24 months after dilatation. CONCLUSION--Organisation and collagenisation of scar tissue develops slowly after balloon dilatation of the aortic valve. This prolonged scarring reaction may explain the late development of restenosis in some patients.

No abstract is provided for this article.