Arterial and Cardiac Remodeling Associated With Extra Weight Gain in an Isolated Abdominal Obesity Cohort

Introduction: This study aims to assess the changes in cardiovascular remodeling attributable to bodyweight gain in a middle-aged abdominal obesity cohort. A remodeling worsening might explain the increase in cardiovascular risk associated with a dynamic of weight gain.Methods: Seventy-five middle-aged subjects (56 ± 5 years, 38 women) with abdominal obesity and no known cardiovascular disease underwent MRI-based examinations at baseline and at a 6.1 ± 1.2-year follow-up to monitor cardiovascular remodeling and hemodynamic variables, most notably the effective arterial elastance (Ea). Ea is a proxy of the arterial load that must be overcome during left ventricular (LV) ejection, with increased EA resulting in concentric LV remodeling.Results: Sixteen obese subjects had significant weight gain (>7%) during follow-up (WG+), whereas the 59 other individuals did not (WG–). WG+ and WG– exhibited significant differences in the baseline to follow-up evolutions of several hemodynamic parameters, notably diastolic and mean blood pressures (for mean blood pressure, WG+: +9.3 ± 10.9 mmHg vs. WG–: +1.7 ± 11.8 mmHg, p = 0.022), heart rate (WG+: +0.6 ± 9.4 min−1 vs. −8.9 ± 11.5 min−1, p = 0.003), LV concentric remodeling index (WG: +0.08 ± 0.16 g.mL−1 vs. WG−: −0.02 ± 0.13 g.mL−1, p = 0.018) and Ea (WG+: +0.20 ± 0.28 mL mmHg−1 vs. WG−: +0.01 ± 0.30 mL mmHg−1, p = 0.021). The evolution of the LV concentric remodeling index and Ea were also strongly correlated in the overall obese population (p < 0.001, R2 = 0.31).Conclusions: A weight gain dynamic is accompanied by increases in arterial load and load-related concentric LV remodeling in an isolated abdominal obesity cohort. This remodeling could have a significant impact on cardiovascular risk.

Optimizing the lithotripsy timing after drainage of the upper urinary tract in patients with urolithiasis and obstructive uropathy

Introduction. Timely unresolved upper urinary tract (UUT) obstruction in patients with infection can cause severe complications, such as sepsis, pyonephrosis and even death. There are no clear recommendations regarding the methods and timing of drainage. At the same time, this issue is still the subject of discussion in publications of recent years.Purpose of the study. To optimize the timing of lithotripsy after drainage of the UUT in patients with urolithiasis and obstructive uropathy (OU).Materials and methods. At the first stage, 90 patients with OU caused by the stone of the ureteropelvic junction underwent drainage of the UUT using a percutaneous nephrostomy. Subsequently, percutaneous nephrolithotripsy (PNLT) was performed at various times after drainage. The level of inflammatory markers (IL-8) and profibrotic factor (MCP-1) in the urine was determined. The calculated concentrations of urinary biomarkers were normalized by the level of urinary creatinine. Urine sampling for the analysis was carried out during and after the PCN placement (nephrostomy urine) 7 days later, and then once weekly before surgery. The coefficient K was calculated using a patented formula to evaluate the process of kidney remodeling. Urine sampling was performed for culture to determine the bacterial spectrum and antibiotic sensitivity.Results. The values of K ≤ 1.85 were observed in 11 patients of the group with OU (12.2%), K > 1.85 in 79 (87.8%) by day 21. The values of K ≤ 1.85 were achieved in 70 patients (88.6%) by day 28 and 4 patients (80.0%) by day 35. PNLT was performed on 21 days in patients with K ≤ 1.85 (11 patients), no complications were noted in the postoperative period., PNLT was performed in patients with K ≤ 1.85 (70 patients) by day 28, exacerbation of pyelonephritis and the development of chronic kidney disease were not noted. Six patients with values of K ˃ 1.85 underwent PNLT by day 28. In the postoperative period, all patients had an exacerbation of calculous pyelonephritis, 50% had a decrease in glomerular filtration rate within 3 months after surgery. The bacteria in urine were detected in 55 (61.0%) patients. Escherichia coli (63.0%), Proteus mirabilis (18.0%), Enterococcus faecalis (14.5%), Streptococcus haemolyticus (2.5%) were identified most often.Conclusion. The use of the developed remodeling index allows optimizing the surgery timing and minimizing the development of complications during the postoperative period. The presence of bacteria is associated with a long process of renal parenchymal remodeling.

Independent predictors of major cardiovascular events as quantitatively assessed by coronary CT-angiography: a long-term follow-up analysis

Introduction Quantitative CT coronary angiography using semi-automated software provides detailed information about plaque volume and high-risk plaque characteristics, beyond traditional measures like diameter stenosis. We assessed the potential value of plaque quantity and morphology to independently predict MACE in a cohort with long-term follow up. Methods In this secondary analysis of 301 symptomatic patients undergoing coronary CTA at baseline, total plaque volume (TPV), non-calcified- (NCPV), calcified- (CPV) and vulnerable coronary plaque volume (in mm3), diameter stenosis (in %) and remodeling index were quantified using semi-automated software (Autoplaque version 2.5, Cedars-Sinai Medical Center, Los Angeles, CA). Patients were followed for major cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction and coronary revascularization. Optimal thresholds for each quantitative CTA measure were computed using CART-algorithm (Classification and Regression Trees). Results Complete follow-up was available for 234 (78%) patients. The mean age was 59±10 years. Over a median follow-up of 10.7 years, the composite outcome occurred in 34 (15%) patients (5 patients with cardiovascular death, 6 with myocardial infarction, 26 with revascularization). Patients experiencing MACE had more frequently hypertension (p=0.03) and a higher Framingham risk score (p=0.002). Survival anaylsis using cox proportional hazard ratios showed significant univariate associations between MACE and TPV (HR 5.16; 95% CI 1.58–16.89; p=0.007), NCPV (HR 4.83; 95% CI 1.45–15.81; p=0.009), CPV (HR 2.86; 95% CI 1.39–5.86; p=0.004), vulnerable plaque volume (HR 3.35; 95% CI 1.52–7.41; p=0.003), diameter stenosis (HR 5.19; 95% CI 2.64–10.22; p<0.001) and remodeling index (HR 4.24; 95% CI 2.03–8.86; p<0.001). In multivariable cox regression analysis diameter stenosis (HR 3.70; 95% CI 1.72–7.93; p=0.001) and remodeling index (HR 2.69; 95% CI 1.19–6.09; p=0.018) remained significant independent predictors of MACE, adjusted for Framingham risk score (HR 2.56; 95% CI 1.26–5.22; p=0.010), however plaque volume and plaque subcomponents did not. Conclusion On long term follow-up, remodeling index and coronary diameter stenosis obtained by quantitative coronary CT angiography independently predicted MACE on multivariable assessment. More comprehensive plaque assessment algorithms including plaque volume as well as plaque subcomponents were significantly associated with MACE in univariate, but not multivariate analysis after adjustment for diameter stenosis and remodeling index. FUNDunding Acknowledgement Type of funding sources: None.

Association of residual stenosis after balloon angioplasty with vessel wall geometries in intracranial atherosclerosis

BackgroundPercutaneous transluminal balloon angioplasty (PTBA) may be an alternative treatment for patients with symptomatic intracranial atherosclerotic disease (ICAD) refractory to medical treatment. This study aimed to investigate the association of vessel wall geometric characteristics on high-resolution magnetic resonance vessel wall imaging (MR-VWI) with low residual stenosis in patients with ICAD after PTBA.MethodsPatients with symptomatic ICAD who underwent PTBA were prospectively and consecutively enrolled. High-resolution MR-VWI was performed before the PTBA. Vessel wall geometries of the target artery, including normalized wall index (NWI: wall area/vessel area × 100%), normalized wall thickness index (NWTI: mean wall thickness/vessel radius × 100%), and remodeling index (RI) were evaluated. Low residual stenosis was defined as postprocedural stenosis degree ≤50%. Perioperative complications including symptomatic ischemic stroke/intracranial hemorrhage, death, and arterial dissection were recorded. The baseline characteristics, vessel wall geometries, and perioperative complications were compared between the patients with low residual stenosis and high residual stenosis.ResultsAmong 60 patients prospectively enrolled, low residual stenosis was achieved in 46 participants (77%). Three patients (5%) suffered from symptomatic ischemic stroke within 30 days. Multivariable logistic regression showed that a lower NWI and lower NWTI were associated with low residual stenosis after PTBA (adjusted OR 0.57, 95% CI 0.35 to 0.94, p=0.027; and adjusted OR 0.88, 95% CI 0.80 to 0.98, p=0.015).ConclusionsLower NWI and NWTI of the target artery on high-resolution MR-VWI were associated with low residual stenosis in patients with ICAD after PTBA.

Adenosine A2a Receptors Improve Hypoxic Pulmonary Arterial Hypertension Via Mitochondrial ATP-sensitive Potassium Channels

IntroductionThis study is aimed to explore the effects of Adenosine A2a receptors (A2aR) on hypoxia-induced pulmonary hypertension (HPH) via mitochondrial ATP-sensitive potassium channels (MitoKATP) in vivo and in vitro.Material and methodsUsing wild-type (WT) and A2aR-deficient (A2aR-/-) mice; hypoxic pulmonary artery smooth muscle cells (PASMCs) were induced by a 24-hours hypoxia exposure. Mice and PASMCs were treated with the A2aR agonist CGS21680, MitoKATP blocker 5-hydroxydecanoic acid sodium salt (5HD), or MitoKATP agonist diazoxide. Mitochondrial morphology was observed by electron microscopy. The mitochondrial membrane potential (Δψm); invasive hemodynamic parameters; right ventricular (RV) hypertrophy index; pulmonary arterial remodeling index; proliferative and apoptotic indexes; protein expression levels of A2aR, Bax, Bcl-2, and Caspase-9; and release of cytochrome C from the mitochondria to the cytoplasm were measured.ResultsIn vitro, hypoxia induced the opening of MitoKATP. The up-regulation of A2aR reduced the opening of MitoKATP, and the blocking of MitoKATP or activating A2aR promoted mitochondria-dependent apoptosis of PASMCs. In vivo, compared with WT mice, A2aR-/- mice displayed increased RV systolic pressure, RV hypertrophy index, and pulmonary arterial remodeling index. The expression levels of Bax, cytochrome C, and Caspase-9 were higher and Bcl-2 expression was lower in A2aR-/- mice than in WT mice. CGS21680 could reverse hypoxia-induced hemodynamic changes, RV hypertrophy, and pulmonary arterial remodeling as well as abnormal proliferation and apoptosis resistance in WT mice with pulmonary hypertension (PH).ConclusionsA2aR induced the mitochondrial-dependent apoptosis pathway and inhibited PASMC proliferation by blocking MitoKATP, thereby inhibiting pulmonary vascular structural remodeling and reducing PH.

Computed Tomography Coronary Angiography Possibilities in “High Risk” Plaque Identification in Patients with non-ST-Elevation Acute Coronary Syndrome: Comparison with Intravascular Ultrasound

Aim To evaluate structural characteristics of atherosclerotic plaques (ASP) by coronary computed tomography arteriography (CCTA) and intravascular ultrasound (IVUS).Material and methods This study included 37 patients with acute coronary syndrome (ACS). 64-detector-row CCTA, coronarography, and grayscale IVUS were performed prior to coronary stenting. The ASP length and burden, remodeling index (RI), and known CT signs of unstable ASP (presence of dot calcification, positive remodeling of the artery in the ASP area, irregular plaque contour, presence of a peripheral high-density ring and a low-density patch in the ASP). The ASP type and signs of rupture or thrombosis were determined by IVUS.Results The IVUS study revealed 45 unstable ASP (UASP), including 25 UASP with rupture and 20 thin-cap fibroatheromas (TCFA), and 13 stable ASP (SASP). No significant differences were found between distribution of TCFA and ASP with rupture among symptom-associated plaques (SAP, n=28) and non-symptom-associated plaques (NSAP, n=30). They were found in 82.1 and 73.3 % of cases, respectively (p>0.05), which indicated generalization of the ASP destabilization process in the coronary circulation. However, the incidence of mural thrombus was higher for SAP (53.5 and 16.6 % of ASP, respectively; p<0.001). There was no difference between UASP and SASP in the incidence of qualitative ASP characteristics or in values of quantitative ASP characteristics, including known signs of instability, except for the irregular contour, which was observed in 92.9 % of UASP and 46.1 % of SASP (p=0.0007), and patches with X-ray density ≤46 HU, which were detected in 83.3 % of UASP and 46.1 % of SASP (р=0.01). The presence of these CT criteria 11- and 7-fold increased the likelihood of unstable ASP (odd ratio (OR), 11.1 at 95 % confidence interval (CI), from 2.24 to 55.33 and OR, 7.0 at 95 % CI, from 5.63 to 8.37 for the former and the latter criterion, respectively).Conclusion According to IVUS data, two X-ray signs are most characteristic for UASP, the irregular contour and a patch with X-ray density ≤46 HU. The presence of these signs 11- and 7-fold, respectively, increases the likelihood of unstable ASP.

Assessment of atherosclerotic plaques morphology and composition by computed tomography coronary angiography: comparison in patients with acute coronary syndrome and stable angina

Цель исследования. Сравнение особенностей строения атеросклеротических бляшек (АСБ) в коронарных артериях (КА) у больных с острым коронарным синдромом (ОКС) и стабильной стенокардией (СС). По данным компьютерной томографии (КТ). Материал и методы. Исследование выполнено у 125 больных: с ОКС (n = 94) и СС (n = 31). КТ КА с использованием томографа с 64 рядами де- текторов проводилась до стентирования КА. Определялись тип, протяженность, бремя АСБ, индекс ремоделирования (ИР), а также признаки нестабильности АСБ: наличие точечных кальцинатов, положительное ремоделирование артерии, неровность контура, наличие кольцевидного усиления плотности по периферии АСБ и участка низкой рентгеновской плотности <46 HU. Результаты. В группе больных с ОКС (n = 250 АСБ) по сравнению со СС (n = 81 АСБ) достоверно чаще определялись мягкие бляшки и до- стоверно реже — кальцинированные: n = 127 (50,8%) и n = 26 (32,1%), p = 0,0046; n = 24 (9,6%) и n = 25 (30,9%), p = 0,0011. При срав- нении совокупности мягких и комбинированных АСБ группы ОКС (n=226) и СС (n=56) в группе с ОКС значение ИР было значимо выше (1,20 [1,14; 1,32] и 1,13 [1,05; 1,25], p = 0,0008), а неровность контура определялась достоверно чаще (n = 170 (75%) и n = 30 (54%), p = 0,003). Наоборот, протяженность поражения была больше в группе больных с СС (18 [15; 21,7] мм и 13 [9; 20] мм, p < 0,0001). При ОКС симптом-связанные бляшки (ССБ, n = 87) отличались от симптом-несвязанных бляшек (СНБ, n = 139) более частым наличием неровности контура (n = 72, 83% и n = 97, 70%, p = 0,040), более высокими значениями бремени (90,0 [80,0; 99,0]% и 70,0 [60,0; 85,0]%, p = 0,0001) и протяженности (15 [10; 22] мм и 12 [8; 18] мм, p = 0,038). Достоверных различий остальных характеристик в сравниваемых подгруппах АСБ выявлено не было. Заключение. При ОКС достоверно чаще определялись мягкие АСБ, а при СС — кальцинированные, при этом в мягких и комбинированных коронарных АСБ в группе больных с ОКС отмечались достоверно более высокий индекс ремоделирования, меньшая протяженность и более частое выявление неровности контура. У пациентов с ОКС отсутствовали достоверные различия значений большинства КТ характеристик АСБ между ССБ и СНБ, что может быть следствием генерализации процесса дестабилизации бляшек в КА. Aim. To compare the structural features of coronary artery (CA) atherosclerotic plaques (ASP) in patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) by computed tomography (CT). Material and methods. The study consists of 125 patients: with ACS (n = 94) and SAP (n = 31). CT angiography (Multislice CT 64; 100-120 ml contrast agent) was performed before coronary angiography. We have estimated type, length, burden of ASP, remodeling index (IR), as well as signs of plaque’s vulnerability — the presence of spotty calcifications, positive remodeling of the artery, rough contour, «ring-like” enhancement and area of low X-ray density < 46 HU. Results. In the group of patients with ACS (n = 250 ASP) compared with SAP (n = 81 ASP) frequency of soft plaques was significantly higher and calcified plaques were significantlylower: n = 127 (50,8%) and n = 26 (32,1%), p = 0,0046; n = 24 (9,6%) and n = 25 (30,9%), p = 0,0011. Comparing only soft and combined ASP inthe ACS group (n = 226) and SAP (n =5 6), in the ACS group, the RI was significantly higher (1,20 [1,14; 1,32] and 1,13 [1,05; 1,25], p = 0,0008), and rough contour was determined significantly more often (n = 170 (75%) and n = 30 (54%), p = 0,003). The length of the lesion was greater in the group of patients with SAP (18 [15; 21,7] mm and 13 [9-20] mm, p < 0,0001). In ACS culprit lessions (n = 87) differed from non-culprit lessions (n = 139) in more frequent presence of rough contour (n = 72, 83%, and n = 97, 70%, p = 0,040), higher values of the burden (90,0 [80,0; 99,0]% and 70,0 [60,0; 85,0]%, p = 0,0001) and length (15 [10; 22] mm and 12 [8; 18] mm, p = 0,038). Conclusion. In ACS soft ASP were significantly more often determined, and in SAP – calcified ones. In ACS, compared with SAP, soft and combined coronary ASP had a significantly higher remodeling index, a shorter length and more frequent detection of contour irregularities. In patients with ACS, there were no significant differences in most of CT plaque’s characteristics between culprit and non-culprit lessions, which may be a consequence of the “generalization of the process plaque’s destabilizing”

Association between near-infrared spectroscopy defined lipid rich plaque and pericoronary adipose tissue inflammation on computed tomography angiography

Background A recent study has shown that lipid-rich plaque (LRP) detected by near-infrared spectroscopy (NIRS) is a significant predictor of future adverse events. Pericoronary adipose tissue inflammation (FAI; fat attenuation index) evaluated by computed tomography angiography (CTA) has also been reported to be linked with cardiac events. The relationship between NIRS-defined LRP and FAI remains to be determined. Methods A total of 82 de novo culprit lesions in 82 patients with chronic coronary syndromes (CCS) who underwent perprocedural CTA and NIRS was retrospectively studied. FAI was assessed by the crude analysis of the mean CT attenuation value (−190 to −30 Hounsfield units; higher values indicating inflammation) of pericoronary adipose tissue. Plaque morphology was assessed by coronary CTA and grey-scale intravascular ultrasound (IVUS). NIRS-defined LRP was defined as a maximum lipid core burden index (LCBI) in 4 mm ≥400. Relationship between NIRS-defined LRP, CTA/grey-scale IVUS findings, and FAI was assessed. Univariate and multivariate logistic regression analyses were performed to determine the predictors for NIRS-derived LRP. Results NIRS-defined LRP was observed in 35 (42.6%) patients. Maximum LCBI showed modest correlations both with FAI (r=0.29, p-value=0.007) and CT-derived remodeling index (r=0.51, p&lt;0.001). Receiver operating characteristic (ROC) curve analysis revealed that the best cut-off values of FAI and CT-derived remodeling index for predicting NIRS-defined LRP were −70.7 (AUC: 0.65, 95% CI: 0.53–0.71, P&lt;0.05) and 1.11 (AUC: 0.74, 95% CI: 0.63–0.86, P&lt;0.01), respectively. Multivariate logistic regression analysis showed FAI ≥−70.7 (odds ratio [OR]: 4.27; 95% CI: 1.28–14.3; p-value = 0.02) and CT-derived remodeling index (OR: 10.7; 95% CI: 2.99–32.2; p-value &lt;0.001) were independent predictors of the presence of NIRS-defined LRP, whereas there was no statistically significant and independent predictor of IVUS-derived factors for NIRS-defined LRP. When stratified according to the presence or absence of FAI ≥−70.7 and CT-derived remodeling index ≥1.11, 93% of the lesions showed NIRS-derived LRP when both factors were present, and NIRS-derived LRP was safely ruled out (88%) when both factors were absent. Conclusions FAI of the culprit lesion in CCS was an independent predictor of NIRS-defined LRP, supporting the notion that local pericoronary adipose tissue inflammation may correlate to the presence of LRP. Comprehensive assessment of coronary CTA including FAI evaluation may provide a highly accurate information with high sensitivity and specificity for identifying high risk lesions potentially leading to future cardiac events. Funding Acknowledgement Type of funding source: None