Potential Clinical Usefulness of Post-Valvular Contrast Densities to Determine the Severity of Aortic Valve Stenosis Using Computed Tomography.

BACKGROUND: Different methods are established for the changes in aortic valve stenosis with cardiac computed tomography angiography (CCTA), but the effect of the grade of stenosis on contrast densities around the valve has not been investigated. AIMS/METHODS: Using the information from flow dynamics in cases of increased velocity through narrowed lumen, the hypothesis was formed that flow changes can alter the contrast densities in stenotic post-valvular regions, and the density changes might correlate with the grade of stenosis. Forty patients with severe aortic stenosis and fifteen with a normal aortic valve were enrolled. With echocardiography, the peak/mean transvalvular gradients, peak transvalvular velocity, and aortic valve opening area were obtained. With CCTA, densities 4-5 mm above the aortic valve; at the junction of the left, right, and noncoronary cusp to the annulus; at the middle level of the left, right, and noncoronary sinuses of Valsalva in the center and the lateral points; at the sinotubular junction; and 4 cm from the sinotubular junction at the midline were measured. First, a comparison of the densities between the normal and stenotic valve was performed, and then possible correlations between echocardiography and CCTA values were investigated in the stenotic group. RESULTS: In all CCTA regions, significantly lower-density values were detected among stenotic valve patients compared to the normal aortic valve population. Additionally, in both groups, higher densities were measured in the peri-jet regions than in the lateral ones. Furthermore, a good correlation was found between the aortic valve opening area and the densities in almost all perivalvular areas. With regard to the densities at the junction of the non-coronary leaflet to the fibrotic annulus and at the most lateral point of the right sinus of Valsalva, a high level of correlation was found between all echocardiography and CCTA parameters. Lastly, with receiver operating characteristic curve measurements, area under the curve values were between 0.857 and 0.930. CONCLUSION: Certain CCTA density values, especially 4-5mm above the valve opening, can serve as auxiliary information to echocardiography when the severity of aortic valve stenosis is unclear.

Differential diagnostic and treatment difficulties in a patient with acquired von Willebrand syndrome.

BACKGROUND: Acquired von Willebrand syndrome (AVWS) is a rare, frequently underdiagnosed and underestimated bleeding disorder. Careful personal and family history and late-onset mucocutaneous bleeding could help clarify the etiology of bleeding deficiency. CASE PRESENTATION: An 82-year-old male patient was admitted to our clinic with a severe nosebleed on 30.05.2018. Laboratory results revealed thrombocytosis, elevated white blood cell count and high LDH. Basic coagulation parameters were normal. He was referred to our clinic, where a bone marrow biopsy was taken. His personal and family history had no mention of bleeding disorders, nor was he on anticoagulant therapy. We detected elevated VWF antigen and decreased VWF ristocetin cofactor activity. Loss of high molecular weight multimers was detected by using agarose gel electrophoresis. These laboratory results were indicative of AVWS. Hydroxyurea treatment was initiated, leading to a gradual decrease in platelet count. The histological examination revealed essential thrombocytosist while mutation analysis was JAK2/CALR/MPL negative. However, due to severe nosebleeds, the patient was hospitalized and needed blood transfusion. A cardiological check-up revealed the progression of aortic valve stenosis. After, balloon-dilation a transcatheter aortic valve implantation was performed. As a result, VWF activity and activity to antigen ratio returned to normal as did multimeric structure. In July 2019, the follow-up examination showed that the patient was in a satisfactory condition, with normal hematological parameters, and no new nosebleed episode occurred. CONCLUSIONS: The patient complained of recurring nosebleeds, which stopped completely after the resolution of both underlying conditions successful cytoreductive treatment of triple-negative ET and transcatheteric aortic valve replacement.

Level of the SARS-CoV-2 receptor ACE2 activity is highly elevated in old-aged patients with aortic stenosis: implications for ACE2 as a biomarker for the severity of COVID-19.

Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin-converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals. About 4 times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (88.3 ± 61.6., n = 111, 20.6 ± 13.4, n = 540, and 16.1 ± 7.4 mU/L, n = 46, respectively). Patients with severe AS were older than patients with hypertension (80 ± 6 years vs. 60 ± 15 years, P < 0.05). Serum ACE2 activity correlated negatively with the left ventricular ejection fraction, aortic root area, TAPSE, and positively with the right ventricular systolic pressure, cardiac diameters in patients with AS. In contrast, circulating ACE2 activity was independent of the blood pressure, peak flow velocity at the aortic root, kidney function (GFR), and inflammatory state (CRP). We found no effect of RAAS inhibitory drugs on the serum ACE2 activity in this group of patients. Our results illustrate circulating ACE2 as a potential interface between chronic inflammation, cardiovascular disease, and COVID-19 susceptibility. Elderly patients with AS have markedly elevated ACE2 levels together with altered left and right ventricular functions, which may pose higher risks during COVID-19. Our clinical data do not support a role for RAAS inhibitors in regulating circulating ACE2 levels.

Effect of patient positioning on the evaluation of myocardial perfusion SPECT.

BACKGROUND: ECG-gated SPECT myocardial perfusion imaging is usually acquired in supine position. However, some patients are not comfortable in this position for a variety of personal or medical reasons. Our aim was to investigate the effect of patient positioning on quantitative SPECT imaging results using normal supine database. METHODS: 55 patients (mean age 58.5 ± 8.3 years) were enrolled in this prospective study. Each patient had a pair of ECG-gated stress SPECT myocardial perfusion images acquired on two gamma cameras: one in supine position and the other in upright sitting position. Left ventricular (LV) ejection fraction (EF), end-diastolic (ED), and end-systolic (ES) left ventricular volumes (V), LV mass, summed stress perfusion defect score (SSS), and total severity score (TSS) were calculated automatically relative to a supine normal reference database. RESULTS: There were no significant differences in LVEF using the two cameras (0.65 ± 0.08 vs. 0.66 ± 0.10; P > 0.1). However, EDV, ESV, and LV mass were significantly smaller in sitting position than in supine position (89 vs. 80 ml; 33 vs. 29 ml and 115 vs. 109 ml, respectively, all P < 0.0001). On the other hand, SSS and TSS were significantly higher in sitting position than in supine position (5.16 vs. 8.73 and 166.82 vs. 288.27, both P < 0.0001). Overall, more studies in sitting position were interpreted as abnormal than in supine position (P < 0.05). CONCLUSION: Patient positioning has a significant impact on quantitative gated SPECT imaging results. Using a supine normal reference database, SSS and TSS were larger in sitting position than in supine position. Thus, for imaging in sitting position, separate normal limits are required.

Relationship between reversibility score on corresponding left ventricular segments and fractional flow reserve in coronary artery disease.

OBJECTIVE: The objective of this study was to find the correlation between the severity of perfusion abnormality detected by scintigraphy and the FFR value, as well as the localization of a particular coronary lesion. On the basis of FFR values and the corresponding left ventricular segments, we proposed a combined index to aim for better correlation with myocardial ischemia than the FFR parameter alone. METHODS: Twenty-eight patients (male: 22, female: 6, age 62±7.62) having FFR measurements and myocardial perfusion SPECT studies were enrolled in our retrospective analysis. FFR measurements on 36 vessels (20 LAD, 6 LCx, 10 RCA) with intermediate stenosis (40%-60%) were compared to the Tc-99m SestaMIBI myocardial perfusion SPECT studies. SPECT studies were performed before the invasive procedure in all cases. We introduced a new ischemic index, the left ventricular ischemic index (LVIi), by combining FFR values with the number of corresponding myocardial segments (N) [LVIi=N x (1-FFR)]. This index correlated with the regional myocardial perfusion defects identified on the scintigrams. A perfusion reversibility score of 2 or above was considered indicative of active ischemia (regional difference score: rDSc). For the statistical analysis, we used linear regression analysis and receiver operating characteristic (ROC) curve analysis to compare the different parameters. RESULTS: A close linear relationship was found between the LVIi and rDSc values (p<0.001) with linear regression analysis. When analyzing all FFR values independently of the localization of the lesions, they also correlated significantly to the rDSc, but this relation was not as close. LVIi predicted active ischemia (≥2 rDSc) on myocardial scintigraphy with 78% sensitivity and 94% specificity when the cutoff value was set to 0.96. FFR alone predicted ischemia on scintigraphy with 72% sensitivity and 94% specificity at the best 0.8 cut-off value. The area under the ROC curve was significantly higher for LVIi than FFR (0.94 vs. 0.87; p<0.05). CONCLUSION: The scintigraphic data indicate that an LVIi >0.96 implies a clinically relevant stenotic lesion. In our opinion, FFR values, weighted with the corresponding left ventricular segments, should be taken into consideration for the best clinical decision-making.