Coronary Flow Velocity Research Articles

Association between Resting Global Longitudinal Strain and Clinical Outcome of Patients Undergoing Stress Echocardiography

Reduced global longitudinal strain (GLS) of the left ventricle is associated with adverse prognosis in healthy subjects and in different cardiovascular conditions. Resting GLS may enable risk assessment independently from stress echocardiography (SE). We assessed whether there is an association of GLS measured at rest before SE with long-term outcome, independent of clinical parameters or reversible wallmotion abnormalities and Doppler coronary flow velocity reserve. Five hundred thirty patients who underwent SE for ischemia evaluation between 2010 and 2012 and who had rest images available were selected. Resting GLS was measured off-line (absolute value <15% was considered abnormal). Cox models were used to examine the association between clinical variables, ejection fraction, SE variables, and resting GLS with mortality and cardiac events (cardiac death and nonfatal myocardial infarction). The independent prognostic value of GLS over known rest and stress variables was assessed. Over a median follow-up of 7.5years, 137 patients died from any cause and 50 had a nonfatal myocardial infarction. Patients with resting GLS <15% had significantly lower event-free survival (log-rank P<.0001). Resting GLS was significantly associated with risk of all-cause death and hard cardiac events, after adjustment for clinical risk factors, reversible wall motion abnormalities, and coronary flow velocity reserve. Adding resting GLS into a model with clinical, rest, and stress imaging variables significantly increased the model C index (P=.031). In a large cohort of patients with suspected coronary artery disease referred for SE, resting GLS <15% was independently associated with mortality and hard cardiac events, incremental to SE data. Model discrimination including resting GLS measurement was comparable to discrimination including SE results.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

Background and AimsMicrovascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID‐19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID‐19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID‐19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID‐19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD.Methods39 patients that were hospitalized with COVID‐19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized.ResultsPatients with COVID‐19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID‐19 had a lower CFVR compared to those with moderate COVID‐19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: −.470), B‐type natriuretic peptide (p < .001, r: −.580), C‐reactive protein (p < .001, r: −.369), interleukin‐6 (p < .001, r: −.597), and d‐dimer (p < .001, r: −.561), with the three latter biomarkers having the highest areas‐under‐curve for predicting CMD.ConclusionsCoronary microvascular dysfunction is common in patients with COVID‐19 and is related to the severity of the infection. CMD may also explain the “cryptic” myocardial injury seen in patients with severe COVID‐19 infection.

Effects of Hyperoxia on Coronary Circulation in Patients with Peripheral Artery Diseases (PAD)

It is well‐known that hyperoxia evokes different effects in patients with different dieaseas conditions. Studies from this lab and others have shown that hyperoxia is a potent coronary vasoconstrictor. Recently, we found that hyperoxia exaggerates systolic blood pressure (BP) response in patients with PAD. The aim of this study is to characterize the coronary circulatory effects of hyperoxia in PAD patients and healthy controls. We recruited 20 PAD patients (14M, 6F, 66 ± 6yrs), and 16 age‐matched control subjects (10M, 6F, 65 ± 8yrs). The ankle‐brachial pressure index (ABI) in the most affected limbs of the patients was 0.58 ± 0.15, compared to the controls ABI of 1.04 ± 0.09. For the hyperoxia procedure the subjects breathed room air for three minutes and 100% oxygen for five minutes. BP and heart rate (HR) were monitored during baseline and hyperoxia. The rate pressure product (RPP), an index of myocardial oxygen consumption, was calculated as the product of systolic BP and HR. Transthoracic Coronary Echocardiography was used to record early and late peak coronary blood flow velocities (CBV1 and CBV2) in the left anterior descending artery. Early and late coronary vascular conductances (peak coronary blood velocity/diastolic blood pressure, CVC1 and CVC2) and coronary perfusion time fraction (CPTF, coronary perfusion time/R‐R interval) were calculated. All data was compared across time and between groups using Repeated Measures Analyses of Variance (RMANOVA).ResultsAt the baseline, RPP and coronary parameters (CBV2, CVC1, and CVC2) were higher in the PAD group compared to controls, also the PAD group showed significantly shorter CPTF. During hyperoxia, CBV1, CBV2, CVC1, and CVC2 decreased to varying degrees in both groups. However, no significant interactions were observed for RPP and all coronary parameters during hyperoxia between the groups (Table). Our findings suggest that the effect of hyperoxia on coronary circulation was not significantly different between PAD and healthy controls.

New Porcine Model of Arteriovenous Fistula Documents Increased Coronary Blood Flow at the Cost of Brain Perfusion.

Background: Arteriovenous fistulas (AVF) represent a low resistant circuit. It is known that their opening leads to decreased systemic vascular resistance, increased cardiac output and other hemodynamic changes. Possible competition of AVF and perfusion of other organs has been observed before, however the specific impact of AVF has not been elucidated yet. Previous animal models studied long-term changes associated with a surgically created high flow AVF. The aim of this study was to create a simple AVF model for the analysis of acute hemodynamic changes. Methods: Domestic female pigs weighing 62.6 ± 5.2 kg were used. All the experiments were held under general anesthesia. The AVF was created using high-diameter ECMO cannulas inserted into femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Near-infrared spectroscopy sensors, flow probes and flow wires were inserted to study brain and heart perfusion. Results: AVF blood flow was 2.1 ± 0.5 L/min, which represented around 23% of cardiac output. We observed increase in cardiac output (from 7.02 ± 2.35 L/min to 9.19 ± 2.99 L/min, p = 0.0001) driven dominantly by increased heart rate, increased pulmonary artery pressure, and associated right ventricular work. Coronary artery flow velocity rose. On the contrary, carotid artery flow and brain and muscle tissue oxygenation measured by NIRS decreased significantly. Conclusions: Our new non-surgical AVF model is reproducible and demonstrated an acute decrease of brain and muscle perfusion.

Association Between Insulin Resistance, Oxidative Stress, Sympathetic Activity and Coronary Microvascular Function in Patients With Early Stage Impaired Glucose Metabolism.

Although acute hyperglycemia and insulin resistance (IR) are risk factors for atherosclerosis development through oxidative stress and sympathetic activation in diabetes mellitus, the association of these factors with coronary microvascular function in the early diabetic stage remains controversial.Methods and Results: Using transthoracic echocardiography, coronary flow velocity (CFV) and its reserve (CFVR) as parameters of coronary microvascular function were measured before and 1 h after an oral glucose tolerance test (OGTT) in 40 patients (aged 59±12 years) without diagnosed diabetes mellitus or coronary artery disease. Plasma glucose, insulin and thiobarbituric acid reactive substance (TBARS; an oxidative stress marker) were measured during the OGTT. IR was evaluated as homeostasis model assessment of IR (HOMA-R). Sympathetic activity was evaluated by using plasma catecholamines after OGTT. CFVR decreased after an OGTT (P<0.0001) mainly because of an increased baseline CFV (P<0.0001). Although the change in CFVR was not associated with the change in TBARS and catecholamines, it was independently associated with HOMA-R on the multivariate regression analysis (β=-0.40, P=0.01). Another multivariate regression analysis revealed that change in baseline CFV was independently associated with HOMA-R (β=0.35, P=0.03). IR, rather than oxidative stress and sympathetic activity, was associated with an increase in baseline CFV and a decline in CFVR during acute hyperglycemia. IR might play an important role in increased myocardial oxygen demand and coronary microvascular dysfunction.

Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy

BackgroundDirect assessment of the coronary microcirculation has long been hampered by the limited spatial and temporal resolutions of cardiac imaging modalities. ObjectivesThe purpose of this study was to demonstrate 3-dimensional (3D) coronary ultrasound localization microscopy (CorULM) of the whole heart beyond the acoustic diffraction limit (<20 μm resolution) at ultrafast frame rate (>1000 images/s). MethodsCorULM was performed in isolated beating rat hearts (N = 6) with ultrasound contrast agents (Sonovue, Bracco), using an ultrasonic matrix transducer connected to a high channel–count ultrafast electronics. We assessed the 3D coronary microvascular anatomy, flow velocity, and flow rate of beating hearts under normal conditions, during vasodilator adenosine infusion, and during coronary occlusion. The coronary vasculature was compared with micro-computed tomography performed on the fixed heart. In vivo transthoracic CorULM was eventually assessed on anaesthetized rats (N = 3). ResultsCorULM enables the 3D visualization of the coronary vasculature in beating hearts at a scale down to microvascular structures (<20 μm resolution). Absolute flow velocity estimates range from 10 mm/s in tiny arterioles up to more than 300 mm/s in large arteries. Fitting to a power law, the flow rate–radius relationship provides an exponent of 2.61 (r2 = 0.96; P < 0.001), which is consistent with theoretical predictions and experimental validations of scaling laws in vascular trees. A 2-fold increase of the microvascular coronary flow rate is found in response to adenosine, which is in good agreement with the overall perfusion flow rate measured in the aorta (control measurement) that increased from 8.80 ± 1.03 mL/min to 16.54 ± 2.35 mL/min (P < 0.001). The feasibility of CorULM was demonstrated in vivo for N = 3 rats. ConclusionsCorULM provides unprecedented insights into the anatomy and function of coronary arteries at the microvasculature level in beating hearts. This new technology is highly translational and has the potential to become a major tool for the clinical investigation of the coronary microcirculation.

Blunted coronary flow velocity reserve is associated with impairment in systolic function and functional capacity in hypertrophic cardiomyopathy

BackgroundCoronary microvascular dysfunction constitutes an important pathophysiological feature in hypertrophic cardiomyopathy (HCM).We aimed to assess the association between impaired coronary flow velocity reserve (CFVR) and ventricular systolic function and functional capacity. MethodsEighty-three patients with HCM were enrolled in this prospective cohort study. Patients underwent echocardiogram to evaluate ventricular performance and CFVR in the left anterior descending artery (LAD) and posterior descending artery (PD). Diastolic coronary flow velocity was measured in basal conditions and in hyperemia. CFVR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). The link between CFVR and biventricular systolic function and peak VO2 was studied. ResultsAge was 55.0(14.4)years, 50 patients (60%) were male; 59 patients (71%) had nonobstructive HCM. Mean CFVR LAD was 1.81(0.49) and CFVR PD was 1.73(0.55). Lower CFVR PD was associated with impaired global longitudinal strain (GLS) 2D (β-estimate:-3.240,95%CI:-4.634;-1.846, p < 0.001), GLS 3D (β-estimate:-2.559,95%CI:-3.932;-1.186, p < 0.001) and area strain (β-estimate:-3.044,95%CI:-5.373;-0.716, p = 0.011). Lower values of CFVR PD related to worse global work index (β-estimate:267.824,95%CI:75.964;459.683, p = 0.007), global constructive work (β-estimate:217.300,95%CI:38.750;395.850, p = 0.018) and global work efficiency (β-estimate:5.656,95%CI:2.229;9.084, p = 0.002). Impaired CFVR LAD (β-estimate:2.826, 95%CI:0.913;4.739, p = 0.004) and CFVR PD (β-estimate:2.801,95%CI:0.657;4.945, p = 0.011) were associated with lower TAPSE. Lower values of CFVR LAD (β-estimate:2.580, 95%CI:0.169;4.991, p = 0.036) and CFVR PD (β-estimate:3.163, 95%CI: 0.721;5.606, p = 0.012) were associated with worse peak VO2. ConclusionLower CFVR was associated with impairment in biventricular systolic function parameters and functional capacity assessed by pVO2.

Feasibility and value of two-dimensional volumetric stress echocardiography.

Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Resistive reserve ratio and microvascular resistance reserve in patients with coronary vasospastic angina.

Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.

A Closed-Loop Modeling Framework for Cardiac-to-Coronary Coupling.

The mechanisms by which cardiac mechanics effect coronary perfusion (cardiac-to-coronary coupling) remain incompletely understood. Several coronary models have been proposed to deepen our understanding of coronary hemodynamics, but possibilities for in-depth studies on cardiac-to-coronary coupling are limited as mechanical properties like myocardial stress and strain are most often neglected. To overcome this limitation, a mathematical model of coronary mechanics and hemodynamics was implemented in the previously published multi-scale CircAdapt model of the closed-loop cardiovascular system. The coronary model consisted of a relatively simple one-dimensional network of the major conduit arteries and veins as well as a lumped parameter model with three transmural layers for the microcirculation. Intramyocardial pressure was assumed to arise from transmission of ventricular cavity pressure into the myocardial wall as well as myocardial stiffness, based on global pump mechanics and local myofiber mechanics. Model-predicted waveforms of global epicardial flow velocity, as well as of intramyocardial flow and diameter were qualitatively and quantitatively compared with reported data. Versatility of the model was demonstrated in a case study of aortic valve stenosis. The reference simulation correctly described the phasic pattern of coronary flow velocity, arterial flow impediment, and intramyocardial differences in coronary flow and diameter. Predicted retrograde flow during early systole in aortic valve stenosis was in agreement with measurements obtained in patients. In conclusion, we presented a powerful multi-scale modeling framework that enables realistic simulation of coronary mechanics and hemodynamics. This modeling framework can be used as a research platform for in-depth studies of cardiac-to-coronary coupling, enabling study of the effect of abnormal myocardial tissue properties on coronary hemodynamics.

Effect of empagliflozin on coronary microvascular function in patients with type 2 diabetes mellitus-A randomized, placebo-controlled cross-over study.

PurposeResults from large scale cardiovascular outcome trials in patients with type 2 diabetes mellitus (DM2) have found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular death and hospitalization for heart failure, but the mechanisms behind the beneficial cardiovascular effects are not fully understood. We tested the hypothesis that the SGLT2i, empagliflozin, improves non-endothelial dependent coronary microvascular function, thereby leading to better cardiac function.MethodsPatients with DM2 followed at the endocrinology outpatient clinic at Bispebjerg University Hospital were included in a double blinded, placebo-controlled cross-over study. Participants were allocated equally to each treatment sequence using simple randomization and treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Echocardiographic parameters of cardiac function were measured, and blood samples were analyzed for a broad panel of cardiovascular biomarkers.ResultsThirteen patients were randomized to each sequence and 10 and 9 completed the study according to protocol, respectively, and were included in the analysis of outcome parameters. We found no improvement in CFVR (change in the empagliflozin period was -0.16 (SD 0.58)). There were no effects on cardiac systolic function or indicators of cardiac filling pressure. Well-known effects of empagliflozin were obtained, such as weight loss and reduction in Hba1c level. Creatinine level increased but remained within normal range. We observed a clear trend of reduction in cardiovascular biomarkers after empagliflozin treatment and increased levels after the placebo period. No serious adverse reactions were reported.ConclusionsDespite effect on weight-loss, Hba1c and biomarkers, treatment with empagliflozin for 12 weeks did not improve CFVR in patients with DM2.

Short-term coronary risk assessment in the elderly population

Abstract Funding Acknowledgements Type of funding sources: None. Background. Atherosclerosis and coronary artery disease (CAD) are a common condition and cause of death in the elderly population. There are difficulties with risk assessment in the elderly as the of their symptomatic status can be challenging due to neuromuscular weakness, physical deconditioning or neurological, orthopaedic, peripheral vascular, or respiratory limitations. Non-invasive coronary artery velocity assessment by Doppler method at rest could be helpful in the elderly population. Aim To evaluate the prognostic role of coronary artery ultrasound assessment in a non-selected elderly population in everyday clinical practice. Methods: 145 patients, aged ≥75years (99 women; 80 ± 4 years), formed the study group. Left coronary artery flows were scanned in addition to conventional echocardiography. During a median follow-up of 26 months, 16 deaths and 2 non-fatal MI occurred. Results: In multivariable analysis, maximal coronary velocity was the only independent predictor for mortality (HR: 1.02, 95%, CI: 1.01-1.04, p &amp;lt; 0.0005), and for mortality/MI (HR: 1.02, 95%, CI: 1.01-1.03, p &amp;lt; 0.0001). The value of 110 cm/s maximal coronary flow velocity in the proximal segments of left arteries was the best predictor for death, sensitivity 50%, specificity 90%, p &amp;lt; 0.005. The annual mortality rate was 16.6% persons/year for patients with elevated coronary flow velocity ≥110 cm/s. The value 81 cm/s was the best predictor for death/MI, sensitivity 61%, specificity 80%, p &amp;lt; 0.0005; annual mortality rate was 11.2% persons/year for patients with elevated coronary flow velocity ≥81 cm/s (p &amp;lt; 0.0001). Conclusion Doppler coronary flow velocity scanning during routine echocardiography is a feasible and valuable tool for assessment of short-term prognosis in elderly patients. Abstract Figure.

Prognostic value of Doppler coronary artery assessment in comparison with other echocardiographic prognostic parameters

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary artery Doppler assessment during routine echocardiography is an established diagnostic tool, that was proved by previous investigators. The prognostic value of impaired coronary flow in left coronary artery was also recently shown in pilot studies [1, 2]. A low feasibility and unknown prognostic value in comparison with other traditional echocardiographic parameters in non-selected population are considered as the main limitations of this method. Aim To evaluate feasibility and the prognostic value of coronary artery ultrasound assessment in a non-selected population in everyday clinical practice in comparison with other echocardiographic parameters. Methods: 581 non-selected patients were screened in prospective cohort study. Left coronary artery flow was scanned in addition to conventional echocardiography. Follow-up period was 12 months. All-cause mortality, myocardial infarction, revascularization, and hospitalization due to heart failure decompensation were defined as major adverse cardiac events (MACE). Results: Feasibility of coronary artery visualization and Doppler assessment was 89.8%. Follow-up was available in 92% of patients; during this period 22 deaths and 1 non-fatal MI occurred, 116 patients had MACE. In univariable analysis age, global longitudinal strain (GLS), left atrium index and maximal coronary velocity were predictors for all-cause death (p &amp;lt; 0.006-0.0001), but ejection fraction was not (p &amp;lt; 0.29). In multivariable analysis maximal coronary velocity (HR: 1.02, 95%, CI: 1.01-1.03, p &amp;lt; 0.0006), age (HR: 1.06, 95%, CI: 1.01-1.11, p &amp;lt; 0.02), and left atrium index (HR: 1.05, 95%, CI: 1.01-1.08, p &amp;lt; 0.007) were independent predictors for all-cause death. Maximal coronary velocity (HR: 1.02, 95%, CI: 1.01-1.03, p &amp;lt; 0.0001), age (HR: 1.03, 95%, CI: 1.01-1.05, p &amp;lt; 0.006), GLS (HR: 0.90, 95%, CI: 0.85-0.96, p &amp;lt; 0.0008) and left atrium index (HR: 1.02, 95%, CI: 1.01-1.04, p &amp;lt; 0.009) were independent predictors for MACE. Conclusion Doppler coronary flow velocity scanning during routine echocardiography is a feasible and valuable tool for assessment of short-term prognosis in non-selected patients. Its short-term prognostic value is better than prognostic value of ejection fraction and global longitudinal strain for the same patients. Abstract Figure. Coronary flow velocity

Microvascular coronary dysfunction affects global longitudinal strain after stress echocardiography

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND. Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. CMD can be identified, in patients with non-obstructive coronary artery disease (CAD), by a reduced transthoracic Doppler-derived coronary flow reserve (CFR), which is an index of coronary arterial reactivity, and can be impaired in both obstructive CAD and CMD. The aim of this study was to investigate the dipyridamole-induced changes of left ventricular (LV) global longitudinal strain (GLS) in patients with CMD. METHODS. 59 patients (39% women, mean age 65.6 ± 6.1 years) with history of chest pain and without obstructive coronary artery disease (CAD) underwent dipyridamole stress echocardiography. Coronary flow was assessed in the left anterior descending coronary artery. Coronary flow reserve (CFR) was determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR &amp;lt; 2. GLS was measured at rest and at peak dose, using automated function imaging, through the positioning of three endocardial markers (two markers at the mitral annulus and one at the apex) in each apical view. Subsequently, the obtained segmental values of GLS were visualized as a bull’s-eye map in a quick and feasible manner. We had optimal left ventricular endocardial tracking in the overall population. In each patient, we used a frame rate of 70 frames/sec for adequate 2D strain analysis. We analyzed GLS at each step of stress test and compared peak-dose values with baseline. RESULTS. Nineteen patients (32%) among the overall population showed CMD. Baseline GLS was significantly lower in patients with CMD (-16.8 ± 2.7 vs. -19.1 ± 3.1, p &amp;lt; 0.01). A different contractile response to dipyridamole infusion was observed between the two groups: GLS significantly increased up to peak dose in patients without CMD (from -19.1 ± 3.1 to -20.2 ± 3.1, p &amp;lt; 0.01), and significantly decreased in patients with CMD (from -16.8 ± 2.7 to -15.8 ± 2.7, p &amp;lt; 0.01). There was a significant inverse correlation between CFR and DGLS (r = -0.82, p &amp;lt; 0.01). CONCLUSIONS. GLS analysis, particularly performed by comparing dipyridamole peak-dose with baseline values, shows that in patients with CMD there is a different response of LV myocardium to stress test. It could be assumed that the inverse correlation between CFR and delta GLS reflects a progressive subclinical worsening of LV myocardial function and lack of LV contractile reserve due to underlying myocardial ischemia. Larger studies could confirm our data. Abstract Figure. Abstract Figure.

Comprehensive stress echocardiography in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf Stress Echo 2020 study group of the Italian Society of Echocardiography and Cardiovascular Imaging Background Stress echocardiography (SE) in hypertrophic cardiomyopathy (HCM) has more to offer beyond dynamic left ventricular outflow obstruction (LVOTO) to capture the functional heterogeneity of the disease. Objectives To determine the feasibility of comprehensive SE in HCM. Methods We prospectively enrolled 235 HCM patients (age = 48 ± 15 years, 113 men) assessed with exercise stress echocardiography (ESE) in 4 centers. ESE modality was semi-supine bicycle in 29 patients in one center, and treadmill in 206 (followed by same-day, same session, adenosine for step D) in another centers. During SE, we assessed stress-induced new regional wall motion abnormalities (RWMA, step A), coronary flow velocity reserve (CFVR) in left anterior descending coronary artery with Doppler (step D) by semi-supine exercise or adenosine, heart rate reserve (peak/rest heart rate) for EKG-based step E, mitral regurgitation (MR) flow for step F, and LVOTO (step G for gradient). A comprehensive SE score was generated from 0 (all parameters normal) to 5 (all abnormal). Results Technical success rate was 100% for all steps, except step D (80% with semi-supine, 100% with adenosine after treadmill) and F (232/235, 99%). Extra-analysis time was &amp;lt; 3 minutes for steps A + D + E + F + G. Rate of abnormal results ranged from 73% for step E (peak/rest heart rate reserve &amp;lt; 1.80) to 1% for step A (inducible RWMA), with intermediate values for step D (CFVR &amp;lt; 2.0, 44%), step F (at least moderate MR, 32%) and step G (LVOTG &amp;gt; 50 mm Hg, 26%): see figure. SE score was 0 in 14 pts (6%), 1 or 2 in 202 patients (86%) and ≥ 3 in 19 patients (8%). Conclusions Comprehensive SE is feasible in HCM with single stress (semi-supine exercise) or hybrid treadmill exercise followed by adenosine for step D. Phenotyping of the multiform manifestations of HCM with a personalized functional blueprint is now possible. Abstract Figure.

A novel sphygmomanometer for central venous pressure assessment during stress echocardiography

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf StressEcho 2030 study group Background. Central venous pressure (CVP) is important in the hemodynamic phenotyping of failing heart, and the usual invasive assessment can be surrogated by a sphygmomanometer for venous pressure (SVEN) which has been recently prototyped and validated. Aim To assess the technical success rate and correlates of CVP measurements by SVEN during stress echocardiography (SE) Methods We evaluated 22 consecutive patients (age 66 ±11 years, 15 men, ejection fraction 60 ±6%) referred for clinically-driven dipyridamole (n = 20, for chest pain) or treadmill (n = 2, for dyspnea) SE with ABCDE protocol (score range from 0= all steps normal, to 5= all steps abnormal). Step A assesses regional wall motion abnormalities (RWMA); step B, B-lines (diastolic function); step C, left ventricular contractile reserve based on force; step D, coronary flow velocity reserve (CFVR) in left anterior descending artery; step E, heart rate reserve (HRR). In each patient, the usual setting of echocardiographic, electrocardiographic and arterial blood pressure monitoring was integrated with CVP measurement by SVEN (right arm, contralateral to the arterial sphygmomanometer arm) with personalized cuff sizes. SVEN measurements of CVP were obtained at rest and peak stress. Results. SVEN preparation and automated analysis required &amp;lt; 5 minutes for positioning, inflation-deflation, acquisition and off-line reading for single measurement. SVEN success rate was 22/22 (100%). CVP did not change during SE (rest = 2.4 ± 0.5 vs stress= 3.7 ± 0.8 mmHg, p = 0.106). Resting CVP was correlated inversely to ejection fraction at rest (r=-0.489, p = 0.021) and at peak stress (r=-0.545, p = 0.001), CFVR (r=-0.505, p = 0.023), HRR (r=-0.503, p = 0.017) and directly to RWMA (r = 0.431, p = 0.045), B-lines at peak stress (r= 0.626, p = 0.002) and left atrial volume index at rest (r= 0.552, p =0.012) and at peak stress (r = 0.648, p = 0.002). CVP was significantly higher in patients with B-Lines at peak stress (Figure). ABCDE score was directly related to CVP (r = 0.560, p = 0.007). Conclusion. SVEN assessment is feasible at rest and during stress with extremely high success rate and only minimal increase in preparation and analysis time. Changes observed are consistent with the expected hemodynamic profile, with CVP increase associated with more B-lines (a sign of pulmonary congestion and elevated pulmonary capillary wedge pressure) and larger left atrium (an integrated barometer of left ventricular end-diastolic pressure). Abstract Figure.

The ischemic cascades in contemporary patients: five distinct phenotypes assessed by ABCDE stress echocardiography

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf Stress Echo 2020 study group of the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) Background The classical pathophysiological cornerstone of stress cardiac imaging is the ischemic cascade: alterations in coronary flow velocity reserve (CFVR) come first, regional wall motion abnormalities (RWMA) second, and global alterations of left ventricular diastolic and systolic function last. Aim To evaluate the ischemic cascade with stress echo (SE) assessed with ABCDE protocol. Methods We analyzed 1616 patients (age 66 ± 10 years, 1156, 72% males) with chest pain and angiographically documented coronary artery disease (CAD): 928 (57.4%) with previous myocardial infarction and 1451 (89.8%) with previous coronary revascularization. CAD patients were studied with ABCDE-SE protocol by 13 certified laboratories of 5 countries. Stress modality was exercise in 427 (26.4%) dobutamine in 173 (10.7%) and vasodilator stress in 1016 (62.9%) patients (dipyridamole in 982 – 60.8% and adenosine in 34 – 2.1% patients). Step A assessed RWMA; step B, B-lines (diastolic function); step C, left ventricular contractile reserve based on force; step D, CFVR in left anterior descending artery; step E, heart rate reserve. SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). Follow up was obtained in all patients. Results Results were abnormal in 350 (21.7) % for step A, 572 (35.4%) for B, 666 (41.2%) for C, 546 (33.5%) for D and 643 (39.8%) for E. The distribution of positivity is shown in figure. The dominant "solitary phenotype" (only one biomarker abnormal during the test) was step A in 10 (0.6%), step B in 124 (7.7%) step C in 100 (6.2%), step D in 64 (4.0%) and step E in 157 (9.7%) patients. The overall sensitivity for CAD detection including each step of ABCDE score (≥1) was 95.7%. During median follow-up of 22 months [IQ range: 13-37 months] 279 coronary revascularizations occurred. ABCDE score predicted coronary revascularization with score 1: HR: 3.182, 95% CI: 1.699-6.067; score 2: HR: 4.921, 95% CI: 2.571-9.420; score 3: HR: 7.234, 95% CI: 3.743-13.979; score 4: HR: 24.570, 95% CI: 13.390-45.086; and score 5: HR: 38.720, 95% CI: 20.975-71.478 Conclusion Inducible ischemia with CAD is characterized by the complexity and multiplicity of diagnostic phenotypes. The overall ABCDE score predicts clinically driven revascularization. Abstract Figure. The 5 circles of ischemia biomarkers

Vasodilator Strain Stress Echocardiography in Suspected Coronary Microvascular Angina.

Background: In patients with Ischemia and non-obstructive coronary artery stenosis (INOCA) wall motion is rarely abnormal during stress echocardiography (SE). Our aim was to determine if patients with INOCA and reduced coronary flow velocity reserve (CVFR) have altered cardiac mechanics using two-dimensional speckle-tracking echocardiography (2DSTE) during SE. Methods: In a prospective, multicenter, international study, we recruited 135 patients with INOCA. Overall, we performed high dose (0.84 mg/kg) dipyridamole SE with combined assessment of CVFR and 2DSTE. The population was divided in patients with normal CVFR (>2, group 1, n = 95) and abnormal CVFR (≤2, group 2, n = 35). Clinical and 2DSTE parameters were compared between groups. Results: Feasibility was high for CFVR (98%) and 2DSTE (97%). A total of 130 patients (mean age 63 ± 12 years, 67 women) had complete flow and strain data. The two groups showed similar 2DSTE values at rest. At peak SE, Group 1 patients showed lower global longitudinal strain (p < 0.007), higher mechanical dispersion (p < 0.0005), lower endocardial (p < 0.001), and epicardial (p < 0.0002) layer specific strain. Conclusions: In patients with INOCA, vasodilator SE with simultaneous assessment of CFVR and strain is highly feasible. Coronary microvascular dysfunction is accompanied by an impairment of global and layer-specific deformation indices during stress.

Long Noncoding RNA AF131217.1 Regulated Coronary Slow Flow-Induced Inflammation Affecting Coronary Slow Flow via KLF4.

IntroductionThis study investigated the correlation between the levels of long noncoding ribonucleic acids (lncRNAs) AF131217.1 and coronary slow flow (CSF).MethodsA total of 22 patients in the high-sensitivity C-reactive protein (hsCRP) group diagnosed with CSF from January 2018 to December 2018 were enrolled in this study. Coronary flow velocity was determined using the thrombolysis in myocardial infarction frame count (TFC) method. Results: LncRNA AF131217.1 expression in the CSF model was activated. Mean TFC was positively correlated with lncRNA AF131217.1 levels and hsCRP levels. LncRNA AF131217.1 induced inflammation factor levels in the in vitro model. Micro ribonucleic acid (miR)-128-3p is a target spot of lncRNA AF131217.1 on the inflammation in vitro model via Kruppel-like factor (KLF) 4. MiR-128-3p reduced inflammation factor levels (tumor necrosis factor alpha, interleukin [IL]-6, IL-1β, and IL-18). Conclusion: Thus, lncRNA AF131217.1 promoted inflammation in the regulated CSF via KLF4 by miR-128-3p.

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging.

Background: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. Purpose: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. Methods: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27–74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10–40 μg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. Results: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967–1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001–0.534; p = 0.019; OR: 1.147; 95% CI: 1.042–1.263; p = 0.005; respectively). Conclusions: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.