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Progression of the Children Using Afflictions Criteria.
Background A large proportion of patients with angina and no obstructive coronary artery disease (ANOCA) has underlying coronary vasomotor dysfunction (CVDys), which can be diagnosed by a coronary function test (CFT). Coronary tortuosity is a common angiographic finding during the CFT. Yet, no data exist on the association between vasomotor dysfunction and coronary tortuosity. Aim To investigate the association between CVDys and coronary tortuosity in patients with ANOCA Methods All consecutive ANOCA patients who underwent clinically indicated CFT between February 2019 and November 2020 were included. CFT included acetylcholine spasm testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose microvascular dysfunction (MVD). MVD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) less then 2.0. Coronary tortuosity, was scored (no, mild, moderate or severe) based on the angles of the curvatures in the left anterior descending (LAD) artery on angiography. Results In total, 228 patients were included (86% female, mean age 56 ± 9 years). We found coronary artery spasm in 81% of patients and MVD in 45% of patients (15% abnormal CFR, 30% abnormal IMR). There were 73 patients with no tortuosity, 114 with mild tortuosity, 41 with moderate tortuosity, and no patients with severe tortuosity. No differences were found in cardiovascular risk factors or medical history, and the prevalence of CVDys did not differ between the no tortuosity, mild tortuosity and moderate tortuosity group (82, 82, and 85%, respectively). Conclusion In this study, CVDys was not associated with coronary tortuosity. Future experimental and clinical studies on the complex interplay between coronary tortuosity, wall shear stress, endothelial dysfunction and coronary flow are warranted.The development of turbulence after transcatheter aortic valve (TAV) implantation may have detrimental effects on the long-term performance and durability of the valves. The characterization of turbulent flow generated after TAV implantation can provide fundamental insights to enhance implantation techniques. A self-expandable TAV was tested in a pulse replicator and the three-dimensional flow field was extracted by means of tomographic particle image velocimetry. The valve was fixed inside a silicone phantom mimicking the aortic root and the flow field was studied for two different supra-annular axial positions at peak systole. Fluctuating velocities and turbulent kinetic energy were compared between the two implantations. Velocity spectra were derived at different spatial positions in the turbulent wakes to characterize the turbulent flow. The valve presented similar overall flow topology but approximately 8% higher turbulent intensity in the lower implantation. In this configuration, axial views of the valve revealed smaller opening area and more corrugated leaflets during systole, as well as more accentuated pinwheeling during diastole. The difference arose from a lower degree of expansion of the TAV's stent inside the aortic lumen. These results suggest that the degree of expansion of the TAV in-situ is related to the onset of turbulence and that a smaller and less regular opening area might introduce flow instabilities that could be detrimental for the long-term performance of the valve. The present study highlights how implantation mismatches may affect the structure and intensity of the turbulent flow in the aortic root.Background Pathogenic variants in phospholamban (PLN, like p. Arg14del), are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in PLN p.Arg14del carriers. During collagen synthesis and breakdown, propeptides are released into the circulation, such as procollagen type I carboxy-terminal propeptide (PICP) and C-terminal telopeptide collagen type I (ICTP). Aim To investigate if PICP/ICTP levels in blood are correlative biomarkers for clinical disease severity and outcome in PLN p.Arg14del variant carriers. Methods Serum and EDTA blood samples were collected from 72 PLN p.Arg14del carriers (age 50.5 years, 63% female) diagnosed with ACM (n = 12), DCM (n = 14), and preclinical variant carriers (n = 46). PICP levels were measured with an enzyme-linked immune sorbent assay and ICTP with a radio immuno-assay. Increased PICP/ICTP ratios suggest a higher collagen deposition. Clinical data including electrocardiographic, and imaging results were adjudicated from medical records. Results No correlation between PICP/ICTP ratios and late gadolinium enhancement (LGE) was found. Moderate correlations were found between the PICP/ICTP ratio and end-diastolic/systolic volume (both r s = 0.40, n = 23, p = 0.06). PICP/ICTP ratio was significantly higher in patients with T wave inversion (TWI), especially in leads V4-V6, II, III, and aVF (p less then 0.022) and in patients with premature ventricular contractions (PVCs) during an exercise tolerance test (p = 0.007). Conclusion High PICP/ICTP ratios correlated with clinical parameters, such as TWI and PVCs. Given the limited size and heterogeneity of the patient group, additional studies are required to substantiate the incremental prognostic value of these fibrosis biomarkers in PLN p.Arg14del patients.Background Cardiovascular involvement is among the main features of MPS disorders and it is also a significant cause of morbidity and mortality. The range of manifestations includes cardiac valve disease, conduction abnormalities, left ventricular hypertrophy, and coronary artery disease. Here, we assessed the cardiovascular manifestations in a cohort of children and adults with MPS I, II, IV, and VI, as well as the impact of enzyme replacement therapy (ERT) on those manifestations. Methods We performed a chart review of 53 children and 23 adults with different types of MPS that had performed echocardiograms from January 2000 until October 2018. Standardized Z scores were obtained for heart chamber sizes according to the body surface area. When available, echocardiographic measurements that were performed before ERT and at least 18 months after that date were used for the assessment of pre- and post-treatment parameters. Results Left side valvular disease was a frequent finding, with mitral and aortic thickenther prevalent cardiovascular manifestations.Background Genetic variants in Scavenger receptor Class B Type 1 (SCARB1) influencing high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) risk were identified by recent genome-wide association studies. Further study of potential functional variants in SCARB1 may provide new ideas of the complicated relationship between HDL-C and CHD. Methods 2000 bp in SCARB1 promoter region was re-sequenced in 168 participants with extremely high plasma HDL-C and 400 control subjects. Putative risk alleles were identified using bioinformatics analysis and reporter-gene assays. Two indel variants, rs144334493 and rs557348251, respectively, were genotyped in 5,002 CHD patients and 5,175 control subjects. The underlying mechanisms were investigated. Results Through resequencing, 27 genetic variants were identified. Results of genotyping in 5,002 CHD patients and 5,175 control subjects revealed that rs144334493 and rs557348251 were significantly associated with increased risk of CHD [odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09 to 1.52, p = 0.003; OR 2.65, 95% CI 1.66-4.24, p = 4.4 × 10-5). Subsequent mechanism experiments demonstrated that rs144334493 deletion allele attenuated forkhead box A1 (FOXA1) binding to the promoter region of SCARB1, while FOXA1 overexpression reversely increased SR-BI expression. MLN8054 Conclusion Genetic variants in SCARB1 promoter region significantly associated with the plasma lipid levels by affecting SR-BI expression and contribute to the susceptibility of CHD.Diabetic cardiomyopathy (DCM) is characterized by microvascular pathology and interstitial fibrosis that leads to progressive heart failure. The mechanisms underlying DCM pathogenesis remain obscure, and no effective treatments for the disease have been available. In the present study, we observed that STK35, a novel kinase, is decreased in the diabetic human heart. High glucose treatment, mimicking hyperglycemia in diabetes, downregulated STK35 expression in mouse cardiac endothelial cells (MCEC). Knockdown of STK35 attenuated MCEC proliferation, migration, and tube formation, whereas STK35 overexpression restored the high glucose-suppressed MCEC migration and tube formation. Angiogenesis gene PCR array analysis revealed that HG downregulated the expression of several angiogenic genes, and this suppression was fully restored by STK35 overexpression. Intravenous injection of AAV9-STK35 viral particles successfully overexpressed STK35 in diabetic mouse hearts, leading to increased vascular density, suppression of fibrosis in the heart, and amelioration of left ventricular function. Altogether, our results suggest that hyperglycemia downregulates endothelial STK35 expression, leading to microvascular dysfunction in diabetic hearts, representing a novel mechanism underlying DCM pathogenesis. Our study also emerges STK35 is a novel gene therapeutic target for preventing and treating DCM.Ventricular tachycardia is the most frequent cause of sudden cardiovascular death in patients with structural heart disease. Radiofrequency ablation is the treatment cornerstone in this population. Main mechanism for structural heart disease-related ventricular tachycardia is re-entry due to presence of slow conduction area within the scar tissue. Electroanatomical mapping with high density catheters can elucidate the presence of both scar (voltage maps) and slow conduction (activation maps). Despite the technological improvements recurrence rate after ventricular tachycardia ablation is high. Cardiac magnetic resonance has demonstrated to be useful to define the location of the scar tissue in endocardium, midmyocardium and/or epicardial region. Furthermore, recent studies have shown that cardiac magnetic resonance can analyse in detail the ventricular tachycardia substrate in terms of core scar and border zone tissue. This detailed tissue analysis has been proved to have good correlation with slow conduction areas and ventricular tachycardia isthmuses in electroanatomical maps. This review will provide a summary of the current role of cardiac magnetic resonance in different scenarios related with ventricular tachycardia in patients with structural heart disease, its limitations and the future perspectives.Background Ischemic mitral regurgitation (IMR) is a common complication of acute ST-elevation myocardial infarction (STEMI). Little is known regarding the impact of IMR over a long period of follow up. Methods Of 3,208 consecutive STEMI patients from a prospective registry, full echocardiographic information was available for 2,985 patients between the years 2000 and 2020. We compared the two decades- 2001 to 2010 and 2011 to 2020, and assessed for the presence of IMR at baseline, 3 (range 2-6) months and 12 (range 10-14) months after the index event. Results One thousand six hundred and sixty six patients were included in the first decade, 1,319 in the second. Mean patient age was 61.3 ± 12.3 years, 21.1% female patients in the first decade vs. 60.9 ± 12.0 years and 22.2% female in the second (p = 0.40 and p = 0.212, respectively). Rates of moderate IMR or above during the index admission were 17.2% in the first period and 9.3% in the second one (p less then 0.001). After 3 months, the rate of IMR was 48.5% for those who suffered from IMR at baseline, vs.
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