Insights into ascending aortic aneurysm: Interactions between biomechanical properties of the aortic wall and tissue biomarkers.

Background: It remains difficult to understand the association between the local mechanical properties of ascending thoracic aorta aneurysm (asTAA), its tissue, and its cellular and molecular changes. The purpose of our study was to investigate the relationship between biomechanical properties, histopathological findings, and tissue biomarkers of asTAA. Methods: Intraoperative asTAA samples from 30 patients were studied. All samples were examined histologically and underwent a tensile test. We determined the tensile strength (σв, MPa), the strain (ε, mm/mm˟%), and the area under the strength-strain curve (S) along with the concentrations of tissue matrix metalloproteinases (MMP-1 et al.) and their inhibitors, their interleukins (IL) -6 -10, and their tumor necrosis factor (TNF) -α. Results: It was found that 43.3 % of asTAA patients had atherosclerosis, 3.3 % had aortitis, and 53.3 % of patients had connective tissue dysplasia. Differences in the studied parameters between these subgroups were not found. Age correlated with ε (r = -0.49) and S (r = -0.54). ε was also associated with media fibrosis degree (r = -0.5), collagen/elastin ratio (r = -0.61), and IL-10 (r = 0.52). IL-10 correlated with collagen/elastin ratio (r = -0.58), TNF-α (r = 0.77), and MMP-1 (r = 0.71). Conclusion: Tissue IL-10 has a protective effect on the elastic structures of the aortic wall and is positively associated with the activity of MMP-1 and pro-inflammatory cytokines. IL-6 is associated with media fibrosis degree, and negatively affects strength-strain parameters of asTAA samples.

Existing and Emerging Approaches to Risk Assessment in Patients with Ascending Thoracic Aortic Dilatation.

Ascending thoracic aortic aneurysm is a life-threatening disease, which is difficult to detect prior to the occurrence of a catastrophe. Epidemiology patterns of ascending thoracic aortic dilations/aneurysms remain understudied, whereas the risk assessment of it may be improved. The electronic databases PubMed/Medline 1966-2022, Web of Science 1975-2022, Scopus 1975-2022, and RSCI 1994-2022 were searched. The current guidelines recommend a purely aortic diameter-based assessment of the thoracic aortic aneurysm risk, but over 80% of the ascending aorta dissections occur at a size that is lower than the recommended threshold of 55 mm. Moreover, a 55 mm diameter criterion could exclude a vast majority (up to 99%) of the patients from preventive surgery. The authors review several visualization-based and alternative approaches which are proposed to better predict the risk of dissection in patients with borderline dilated thoracic aorta. The imaging-based assessments of the biomechanical aortic properties, the Young's elastic modulus, the Windkessel function, compliance, distensibility, wall shear stress, pulse wave velocity, and some other parameters have been proposed to improve the risk assessment in patients with ascending thoracic aortic aneurysm. While the authors do not argue for shifting the diameter threshold to the left, they emphasize the need for more personalized solutions that integrate the imaging data with the patient's genotypes and phenotypes in this heterogeneous pathology.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Absolute myocardial blood flows derived by dynamic CZT scan vs invasive fractional flow reserve: Correlation and accuracy.

PURPOSE: To define the diagnostic power of absolute myocardial blood flow (MBF) evaluation on dynamic CZT imaging in intermediate risk patients in comparison with invasive coronary angiography (ICA) and fractional flow reserve (FFR). METHODS: Twenty-three stable CAD patients underwent one-day dynamic rest-stress 99mTc-Sestamibi myocardial perfusion imaging by CZT camera. Stress and rest MBF values were calculated semi-automatically using a net retention model by Leppo. Coronary flow reserve (CFR) and flow difference (FD) [MBF stress - MBF rest] were also estimated. A total of 28 vessels were functionally quantified with FFR: 19 (68%) vessels with a stenosis ≥ 70% and 9 (32%) with < 70% stenotic lesions. RESULTS: The mean global MBFs at rest and during stress were 0.36 (IQR 0.33-0.54) mL/min/g and 0.67 (IQR 0.55-0.81) mL/min/g, respectively, with an average CFR of 1.80 (IQR 1.35-2.24). Moderate correlations between stenosis severity and FFR (r = 0.45; P = .01), stress MBF (r = -0.46; P = .01) and FD (r = -0.37; P = .04) were detected. FFR abnormalities were best predicted by absolute stress MBF, CFR and FD with values of ≤ 0.54 mL/min/g (sensitivity 61.5%; specificity 93.3%), ≤ 1.48 (sensitivity 69.2%; specificity 93.3%) and ≤ 0.18 mL/min/g (sensitivity 69.2%; specificity 100%), respectively. CONCLUSIONS: The values of stress MBF, CFR and FD obtained through dynamic CZT acquisitions compare well with invasive FFR. The clinical use of dynamic acquisition of myocardial perfusion imaging by CZT may help cardiologist in the detection of hemodynamically significant CAD.

Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis.

The purpose of the review is the analysis of clinical and experimental data on the etiology and pathogenesis of takotsubo syndrome (TS). TS is characterized by contractile dysfunction, which usually affects the apical region of the heart without obstruction of coronary artery, moderate increase in myocardial necrosis markers, prolonged QTc interval (in 50% of patients), sometimes elevation of ST segment (in 19% of patients), increase N-Terminal Pro-B-Type Natriuretic Peptide level, microvascular dysfunction, sometimes spasm of the epicardial coronary arteries (in 10% of patients), myocardial edema, and life-threatening ventricular arrhythmias (in 11% of patients). Stress cardiomyopathy is a rare disease, it is observed in 0.6 - 2.5% of patients with acute coronary syndrome. The occurrence of takotsubo syndrome is 9 times higher in women, who are aged 60-70 years old, than in men. The hospital mortality among patients with TS corresponds to 3.5% - 12%. Physical or emotional stress do not precede disease in all patients with TS. Most of patients with TS have neurological or mental illnesses. The level of catecholamines is increased in patients with TS, therefore, the occurrence of TS is associated with excessive activation of the adrenergic system. The negative inotropic effect of catecholamines is associated with the activation of ß2 adrenergic receptors. An important role of the adrenergic system in the pathogenesis of TS is confirmed by studies which were performed using 125I-metaiodobenzylguanidine (125I -MIBG). TS causes edema and inflammation of the myocardium. The inflammatory response in TS is systemic. TS causes impaired coronary microcirculation and reduces coronary reserve. There is a reason to believe that an increase in blood viscosity may play an important role in the pathogenesis of microcirculatory dysfunction in patients with TS. Epicardial coronary artery spasm is not obligatory for the occurrence of TS. Cortisol, endothelin-1 and microRNAs are challengers for the role of TS triggers. A decrease in estrogen levels is a factor contributing to the onset of TS. The central nervous system appears to play an important role in the pathogenesis of TS.

Right Atrial Thrombosis and Pulmonary Embolism: A Narrative Review.

Prompt diagnosis of pulmonary embolism (PE) remains challenging, which often results in a delayed or inappropriate treatment of this life-threatening condition. Mobile thrombus in the right cardiac chambers is a neglected cause of PE. It poses an immediate risk to life and is associated with an unfavorable outcome and high mortality. Thrombus residing in the right atrial appendage (RAA) is an underestimated cause of PE, especially in patients with atrial fibrillation. This article reviews achievements and challenges of detection and management of the right atrial thrombus with emphasis on RAA thrombus. The capabilities of transthoracic and transesophageal echocardiography and advantages of three-dimensional and two-dimensional echocardiography are reviewed. Strengths of cardiac magnetic resonance imaging (CMR), computed tomography, and cardiac ventriculography are summarized. We suggest that a targeted search for RAA thrombus is necessary in high-risk patients with PE and atrial fibrillation using transesophageal echocardiography and/or CMR when available independently on the duration of the disease. High-risk patients may also benefit from transthoracic echocardiography with right parasternal approach. The examination of high-risk patients should involve compression ultrasonography of lower extremity veins along with the above-mentioned technologies. Algorithms for RAA thrombus risk assessment and protocols aimed at identification of patients with RAA thrombosis, who will potentially benefit from treatment, are warranted. The development of treatment protocols specific for the diverse populations of patients with right cardiac thrombosis is important.

Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography.

OBJECTIVES: The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE). BACKGROUND: B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE. METHODS: The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up. RESULTS: According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction. CONCLUSIONS: Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020-The International Stress Echo Study [SE2020]; NCT03049995).

Functional, Anatomical, and Prognostic Correlates of Coronary Flow Velocity Reserve During Stress Echocardiography.

BACKGROUND: The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA). OBJECTIVES: The purpose of this study was to assess the feasibility and functional correlates of CFVR. METHODS: This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. A subset of 1,867 patients was followed up. RESULTS: The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome. CONCLUSIONS: CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome.

Transthoracic echocardiography in the detection of chronic total coronary artery occlusion.

AIMS: The aim of our study was to detect chronic total occlusion of the left anterior descending coronary artery (LAD), circumflex coronary artery (Cx), and right coronary artery (RCA) using transthoracic echocardiography (TTE) in 110 consecutive patients who underwent coronary angiography for investigation of angina. METHODS AND RESULTS: Coronary blood flow direction was assessed in the epicardial collaterals [distal LAD (dLAD), obtuse marginal branches and right posterior descending artery (PDA)] and intramyocardial collaterals [LAD septal branch (SB LAD) and RCA septal branch (SB RCA)]. The sensitivity and specificity of retrograde flow for identification of the occluded LAD by TTE in the dLAD only were 78 and 96%, respectively, and those in both dLAD and SB LAD were 89 and 96%, respectively. The retrograde SB LAD flow detects proximal LAD occlusion with 88% sensitivity and 75% specificity. The sensitivity and specificity of retrograde flow for identification of the occluded RCA by TTE in the PDA only were 79 and 97%, respectively, and those in both PDA and SB RCA were 89 and 97%, respectively. The retrograde SB RCA flow does not allow us to differentiate between proximal and non-proximal RCA occlusion. Transthoracic echocardiography is not a method for diagnosing Cx occlusions as the success in visualizing the Cx epicardial collaterals was achieved in 31% of cases only. CONCLUSION: TTE is a sensitive and highly specific non-invasive method for diagnosis of LAD and RCA occlusions, based on the detection of the coronary blood flow direction in the epicardial and intramyocardial collaterals.

Reduced coronary flow reserve in the coronary sinus is a predictor of hemodynamically significant stenoses of the left coronary artery territory.

AIM AND METHODS: The role of transesophageal Doppler assessment of coronary flow reserve (CFR) in the coronary sinus (CS) in the diagnostics of significant left coronary artery (LCA) stenoses was studied in 65 CAD patients with angiographically proven >50% stenotic atherosclerosis of the LCA territory (38--with isolated left anterior descending artery (LAD) or left circumflex artery (Cx) stenosis; 27--with both LAD and Cx stenoses) and 31 healthy volunteers (all men). Dipyridamole was used as a stress agent. The antegrade phase of coronary flow in the CS moving into the right atrium was analysed. CFR in the CS was calculated in two ways: (1) as ratio of hyperemic to baseline peak antegrade flow velocity (CFRp); (2) as ratio of hyperemic to baseline volumetric blood flow velocity (CFRv). The level of CFR <2.0 in both ways of calculation was diagnosed as reduced. RESULTS: CAD patients compared with healthy volunteers had significantly lower CFRp (1.51+/-0.44 and 2.57+/-0.79; p<0.001) and CFRv (2.21+/-1.18 and 5.43+/-2.83; p < 0.001) in the CS. CFRp <2.0 in the CS was a predictor of significant stenoses of the LCA with sensitivity of 89% and specificity of 76%, while CFRv <2.0 was a predictor of significant stenoses of the LCA with sensitivity of 49% and specificity of 97%. CFRp <2.0 in the CS was registered in 96% of CAD patients with two-vessel lesion and in 84% of CAD patients with one-vessel lesion, while CFRv <2.0 in the CS was revealed in 85% of CAD patients with two-vessel lesion and only in 26% of CAD patients with one-vessel lesion. Sensitivity and specificity of CFRv <2.0 in the CS in the diagnostics of significant two-vessel lesion of the LCA were 85% and 84%, respectively. CONCLUSIONS: Thus, the reduced CFR in the CS is a sensitive and specific predictor of LCA stenoses. A decrease of both CFRp <2 and CFRv <2.0 in the CS is a predictor of significant two-vessel lesion of the LCA, while a decrease of only CFRp <2.0 in the CS is a predictor of significant one-vessel lesion of the LCA.