Acetylsalicylic acid use and development of cardiac allograft vasculopathy: A national prospective study using highly automated 3-D optical coherence tomography analysis.

BACKGROUND: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). METHODS: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. RESULTS: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.

Metals and Trace Elements in Calcified Valves in Patients with Acquired Severe Aortic Valve Stenosis: Is There a Connection with the Degeneration Process?

BACKGROUND: Acquired calcified aortic valve stenosis is the most common valve disease in adulthood. In the etiopathogenesis of this complex pathology, the importance of inflammation is mentioned, in which non-infectious influences represented by the biological effects of metal pollutants may participate. The main goal of the study was to determine the concentration of 21 metals and trace elements-aluminium (Al), barium (Ba), cadmium (Cd), calcium (Ca), chrome (Cr), cobalt (Co), copper (Cu), gold (Au), lead (Pb), magnesium (Mg), mercury (Hg), molybdenum (Mo), nickel (Ni), phosphorus (P), selenium (Se), strontium (Sr), sulfur (S), tin (Sn), titanium (Ti), vanadium (V) and zinc (Zn)-in the tissue of calcified aortic valves and to compare them with the concentrations of the same elements in the tissue of healthy aortic valves in the control group. MATERIAL AND METHODS: The study group consisted of 49 patients (25 men, mean age: 74) with acquired, severe, calcified aortic valve stenosis with indicated heart surgery. The control group included 34 deceased (20 men, median age: 53) with no evidence of heart disease. Calcified valves were explanted during cardiac surgery and deep frozen. Similarly, the valves of the control group were removed. All valves were lyophilized and analyzed by inductively coupled plasma mass spectrometry. The concentrations of selected elements were compared by means of standard statistical methods. RESULTS: Calcified aortic valves contained significantly higher (p < 0.05) concentrations of Ba, Ca, Co, Cr, Mg, P, Pb, Se, Sn, Sr and Zn and-in contrast-lower concentrations of Cd, Cu, Mo, S and V than valves of the control group. Significant positive correlations of concentrations between the pairs Ca-P, Cu-S and Se-S and strong negative correlations between the elements Mg-Se, P-S and Ca-S were found in the affected valves. CONCLUSION: Aortic valve calcification is associated with increased tissue accumulation of the majority of the analyzed elements, including metal pollutants. Some exposure factors may increase their accumulation in the valve tissue. A relationship between exposure to environmental burden and the aortic valve calcification process cannot be ruled out. Advances in histochemical and imaging techniques allowing imaging of metal pollutants directly in valve tissue may represent an important future perspective.

Role of genetics in the development of cardiac allograft vasculopathy.

BACKGROUND: The association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options. METHODS: This prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Type assays and Fluidigm 48.48 Dynamic Array IFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx). RESULTS: During the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p < 0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p < 0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added. CONCLUSION: Results of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

Donor specific anti-HLA antibodies and cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis.

INTRODUCTION: Recent studies suggested potential positive correlations between HLA-specific antibodies and development of cardiac allograft vasculopathy (CAV). METHODS: This prospective two-center study investigated early progression of CAV by coronary optical coherence tomography in 1 month and 12 months after heart transplantation (HTx) in 104 patients. Detection and characterization of donor specific (DSA) and MHC class-I polypeptide-related sequence A (MICA) antibodies were performed before, 1, 6 and 12 months after transplantation. RESULTS: During the first post-HTx year, we observed a significant reduction in the mean coronary luminal area (P < .001), and progression in mean intimal thickness (IT) (P < .001). DSA and anti-MICA occurred in 17% of all patients, but no significant relationship was observed between presence of DSA/anti-MICA and IT progression within 12 months after HTx. In contrast, we observed significant association between presence of DSA (p=0.031), de-novo DSA (p=0.031), HLA Class II DSA (p=0.017) and media thickness (MT) progression. CONCLUSION: Results of our study did not identify a direct association between presence of DSA/anti-MICA and intimal thickness progression in an early period after HTx. However, we found significant relationships between DSA and media thickness progression that may identify a newly recognized immune-pathological aspect of CAV.

Heart rate and early progression of cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis.

INTRODUCTION: Heart rate slowing agents are frequently prescribed to manage heart transplant (HTx) patients with the assumption that higher heart rate is a risk factor in cardiovascular disease. PATIENTS AND METHODS: This prospective two-center study investigated early progression of cardiac allograft vasculopathy (CAV) in 116 HTx patients. Examinations by coronary optical coherence tomography and 24-hour ambulatory ECG monitoring were performed both at baseline (1 month after HTx) and during follow-up (12 months after HTx). RESULTS: During the first post-HTx year, we observed a significant reduction in the mean coronary luminal area from 9.0 ± 2.5 to 8.0 ± 2.4 mm2 (P < .001), and progression in mean intimal thickness (IT) from 106.5 ± 40.4 to 130.1 ± 53.0 µm (P < .001). No significant relationship was observed between baseline and follow-up mean heart rates and IT progression (R = .02, P = .83; R = -.13, P = .18). We found a mild inverse association between beta-blocker dosage at 12 months and IT progression (R = -.20, P = .035). CONCLUSION: Our study did not confirm a direct association between mean heart rate and progression of CAV. The role of beta blockers warrants further investigation, with our results indicating that they may play a protective role in early CAV development.

Early detection of cardiac allograft vasculopathy using highly automated 3-dimensional optical coherence tomography analysis.

BACKGROUND: Optical coherence tomography (OCT)-based studies of cardiac allograft vasculopathy (CAV) published thus far have focused mainly on frame-based qualitative analysis of the vascular wall. Full capabilities of this inherently 3-dimensional (3D) imaging modality to quantify CAV have not been fully exploited. METHODS: Coronary OCT imaging was performed at 1 month and 12 months after heart transplant (HTx) during routine surveillance cardiac catheterization. Both baseline and follow-up OCT examinations were analyzed using proprietary, highly automated 3D graph-based optimal segmentation software. Automatically identified borders were efficiently adjudicated using our "just-enough-interaction" graph-based segmentation approach that allows to efficiently correct local and regional segmentation errors without slice-by-slice retracing of borders. RESULTS: A total of 50 patients with paired baseline and follow-up OCT studies were included. After registration of baseline and follow-up pullbacks, a total of 356 ± 89 frames were analyzed per patient. During the first post-transplant year, significant reduction in the mean luminal area (p = 0.028) and progression in mean intimal thickness (p = 0.001) were observed. Proximal parts of imaged coronary arteries were affected more than distal parts (p < 0.001). High levels of LDL cholesterol (p = 0.02) and total cholesterol (p = 0.031) in the first month after HTx were the main factors associated with early CAV development. CONCLUSIONS: Our novel, highly automated 3D OCT image analysis method for analyzing intimal and medial thickness in HTx recipients provides fast, accurate, and highly detailed quantitative data on early CAV changes, which are characterized by significant luminal reduction and intimal thickness progression as early as within the first 12 months after HTx.