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Background: Bolus thermodilution and intravenous adenosine are established methods for coronary microcirculatory assessment. Yet, its adoption remains low, partly due to procedural time and patient discomfort associated with intravenous adenosine. We investigated differences between intracoronary and intravenous adenosine using bolus thermodilution in terms of microcirculatory indices, procedural time, and side effects associated with adenosine in patients with myocardial ischemia and nonobstructive coronary arteries., Methods and Results: In this prospective, observational study, 102 patients with suspected myocardial ischemia and nonobstructive coronary arteries underwent measurements of mean transit time, coronary flow reserve, index of microcirculatory resistance, procedure time and patient tolerability with low-dose intracoronary adenosine, high-dose intracoronary adenosine (HDIC), and intravenous adenosine. HDIC induced greater hyperemia compared with low-dose intracoronary IC adenosine and intravenous adenosine with a shorter hyperemic mean transit time, P <0.0001. Coronary flow reserve was higher and index of microcirculatory resistance lowest with HDIC, compared with low-dose intracoronary IC adenosine and intravenous adenosine, P <0.05. Low coronary flow reserve was downgraded from 21% with intravenous adenosine to 10% with HDIC adenosine ( P =0.031); high index of microcirculatory resistance was downgraded from 23% with intravenous adenosine to 14% with HDIC ( P =0.098). Intracoronary adenosine was associated with lower procedural times ( P <0.0001). More patients experienced chest pain with intravenous adenosine ( P <0.01) and the chest pain intensity was higher compared with intracoronary adenosine ( P <0.0001)., Conclusions: In patients with suspected myocardial ischemia and nonobstructive coronary arteries undergoing coronary microcirculatory assessment with bolus thermodilution, the use of HDIC compared with intravenous adenosine was associated with enhanced induction of hyperemia. The use of intracoronary adenosine allowed for a shorter procedure time and was better tolerated., Registration+: URL: clinicaltrials.gov; Unique Identifier: NCT04827498.

This retrospective cohort study aimed to examine changes in coronary blood flow before and after post-dilation following primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). 419 eligible patients who underwent PPCI due to STEMI between January 2019 and September 2023 were enrolled. The corrected thrombolysis in myocardial infarction frame count (CTFC), final quantitative coronary angiography, and the incidence of no-reflow and slow-flow during different procedure moments were assayed. The changes in coronary blood flow before and after post-dilation in the post-dilation group were analyzed. Among the 419 patients enrolled, 259 patients underwent post-dilation. The post-dilation procedure was more frequently performed in patients with calcium plaque present, longer stents, bigger-diameter stents, and overlapping stents. The incidence of final no-reflow and slow-flow in the post-dilation group was not significantly higher than that observed in the non-post-dilation group. In contrast post-dilation patients had significantly increased CTFC values by 3.54 ± 10.54 frames (P < .001) and the rate of no-reflow/slow-flow increased on average by 114% (P < .001) in comparison to patients not undergoing post-dilation. The receiver operating characteristic curve showed that if post-dilation was performed in patients when their after-stent CTFC was smaller than 23.25, no-reflow/slow-flow was less likely to occur (63.5% sensitivity, 88.8% specificity, [AUC]: 0.817, 95% CI: 0.749-0.886, P < .001). Post-dilation exacerbates the coronary blood flow and increases the incidence of no-reflow/slow-flow during PPCI for STEMI patients, except where after-stend CTFC values were <23.25., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Angina with Non-Obstructed Coronary Arteries (ANOCA) involves abnormal vasomotor responses. While reduced coronary flow is an established contributor to myocardial hypoxia, myocardial blood volume (MBV) independently regulates myocardial oxygen uptake but its role in ANOCA remains unclear., Objectives: We hypothesized that reduced MBV contributes to ANOCA, and associates with insulin resistance in ANOCA., Methods: MBV in ANOCA patients was compared to age- and sex-matched healthy controls. ANOCA patients underwent coronary angiography with invasive coronary function testing (CFT) to identify vasospasm and coronary microvascular dysfunction. In all subjects MBV was quantified at baseline, during hyperinsulinemia and during dobutamine-induced stress using myocardial contrast echocardiography (MCE). The hyperinsulinemic-euglycemic clamp was used to assess insulin resistance., Results: Twenty-eight ANOCA patients (21% men, 56.8 ± 8.6 years) and 28 healthy controls (21% men, 56.5 ± 7.0 years) were included. During CFT 11% of patients showed epicardial vasospasm, 39% microvascular vasospasm, 25% coronary microvascular dysfunction, and 11% of patients had a negative CFT. ANOCA patients had significant lower insulin-sensitivity (p < 0.01). During MCE, ANOCA patients showed a significantly lower MBV at baseline (0.388 vs 0.438 mL/mL, p = 0.04), during hyperinsulinemia (0.395 vs 0.447 mL/mL, p = 0.02), and during dobutamine-induced stress (0.401 vs 0.476 mL/mL, p = 0.030)., Conclusions: In ANOCA patients MBV is diminished at baseline, during hyperinsulinemia and dobutamine-induced stress in the absence of differences in microvascular recruitment. These findings support the presence of capillary rarefaction in ANOCA patients. ANOCA patients showed metabolic insulin resistance, but insulin did not acutely alter myocardial perfusion., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The aspects of extracorporeal cardiopulmonary resuscitation critical for reestablishing an organized rhythm and subsequent functional survival are unclear. This study characterizes the impact of reperfusion with extracorporeal membrane oxygenation (ECMO) and percutaneous coronary interventions (PCI) on achieving an organized rhythm in patients with refractory shockable out-of-hospital cardiac arrest (OHCA)., Methods and Results: Two hundred eighty-nine consecutive patients in refractory shockable OHCA were placed on ECMO followed by coronary angiogram (n=289) and PCI (n=165). Patients were grouped based on the extracorporeal cardiopulmonary resuscitation stage where a sustained organized rhythm was achieved. Survival outcomes were evaluated by using the Cerebral Performance Category. Logistic regression analysis was performed to determine the relationship between Cerebral Performance Category and timing of organized rhythm. Standard advanced cardiac life support before hospital arrival resulted in 148 of 289 (51%) patients attaining an organized rhythm while 87 of 289 (30%) achieved an organized rhythm post ECMO cannulation but before PCI, and 37 of 289 (13%) achieved an organized rhythm following PCI. Obstructive coronary artery disease was observed in 192 of 289 (66%) patients. A total of 144 of 192 (75%) patients with obstructive coronary artery disease converted to an organized rhythm before PCI and 37 of 192 (19%) following PCI. Cerebral Performance Category score 1 or 2 was significantly more likely in patients with cardiac arrest and obstructive coronary artery disease who achieved an organized rhythm before PCI (odds ratio [OR], 3.9 [95% CI, 1.2-12.0], P =0.024)., Conclusions: Most patients undergoing extracorporeal cardiopulmonary resuscitation for refractory OHCA due to shockable rhythms achieved an organized rhythm before PCI independent of coronary artery disease burden. Also, neurologically favorable survival was more prevalent in those attaining an organized rhythm before PCI.

Background: Orthostatic hypotension (OH) is associated with different cardiovascular diseases, however, the association between OH and coronary slow flow (CSF) has never been evaluated before., Materials and Methods: Chest pain patients who underwent coronary angiography (CAG) and with normal coronary arteries in our department from January 1st, 2022 to August 31st, 2023 were retrospectively enrolled. Patients were divided into the CSF group and the normal blood flow (NBF) group. Relative clinical information, laboratory test results as well as the results of CAG were collected and analyzed. Both uni-variable and multi-variable logistic regression analyses were used to evaluate the association between OH and CSF in these patients., Results: Four thousand six hundred and twenty-seven patients underwent CAG and 655 patients had normal coronary arteries. In which, sixty-nine patients were diagnosed with CSF while 586 patients were diagnosed with NBF. Uni-variable analysis revealed that higher body weight index, faster heart rate in sitting position, accompanied with chronic kidney disease, did not take Antidiabetic therapy, higher level of aspartate transaminase, uric acid, triglyceride, total cholesterol, ApoB1, low-density lipoprotein cholesterol, homocysteine, B-type natriuretic peptide as well as OH are the risk factors for CSF in these patients. Multi-variable logistic regressing analysis further demonstrated that OH was the independent risk factor for predicting CSF in these patients., Conclusions: Our finding suggests OH might be a useful predictor for CSF in patients with chest pain but normal coronary arteries., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

In this study, risk factors for coronary slow flow (CSF) patients were examined, and a clinical prediction model was created. This study involved 573 patients who underwent coronary angiography at our hospital because of chest pain from January 2020 to April 2022. They were divided into CSF group (249 cases) and noncoronary slow flow (NCF) group (324 cases) according to the coronary blood flow results. According to a 7:3 ratio, the patients were categorized into a training group consisting of 402 cases and a validation group consisting of 171 cases. The outcome was assessed by employing multiple logistic regression analysis to examine the factors that influenced it. The model's recognizability was assessed by calculating the consistency index and plotting the receiver operating characteristic curve. Its consistency was assessed by calibration curve, decision curve, and Hosmer-Lemeshow testing goodness-of-fit. The multivariate model included factors such as male, BMI, smoking, diabetes, ursolic acid, and high-density lipoprotein cholesterol. The model validation showed that the consistency index was 0.714, and the external validation set had a consistency index of 0.741. The areas under the curve for the training and external validation sets were respectively 0.730 (95% CI: 0.681-0.779) and 0.770 (95%CI: 0.699-0.841). Nomogram calibration curves indicated intense calibration, and the results of the Hosmer-Lemeshow goodness-of-fit test indicated that χ² = 1.118, P = .572. The nomogram combining various risk factors can be used for individualized predictions of CSF patients and then facilitate prompt and specific treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Coronary microvascular dysfunction is a clinical condition very diffuse in many different settings. Often the diagnosis can be very tricky, and choosing the proper diagnostic strategy can be fundamental for reaching the goal. The aim of this review is to evaluate the properties and the feasibility of our tests in specific scenarios by looking at the performances of each methodology reported in the literature., (© 2024 Wiley Periodicals LLC.)

Background: The pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited., Objectives: We sought to evaluate CMD in patients with TTS., Methods: Consecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks., Results: Thirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %)., Conclusion: CMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We develop a machine learning (ML) model using electrocardiography (ECG) to predict myocardial blood flow reserve (MFR) and assess its prognostic value for major adverse cardiovascular events (MACEs). Using 3,639 ECG-positron emission tomography (PET) and 17,649 ECG-single-photon emission computed tomography (SPECT) data pairs, the ML model is trained with a swarm intelligence approach and support vector regression (SVR). The model achieves a receiver-operator curve (ROC) area under the curve (AUC) of 0.83, with a sensitivity and specificity of 0.75. An ECG-MFR value below 2 is significantly associated with MACE, with hazard ratios (HRs) of 3.85 and 3.70 in the discovery and validation phases, respectively. The model's C-statistic is 0.76, with a net reclassification improvement (NRI) of 0.35. Validated in an independent cohort, the ML model using ECG data offers superior MACE prediction compared to baseline clinical models, highlighting its potential for risk stratification in patients with coronary artery disease (CAD) using the accessible 12-lead ECG., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Female Pacific salmon often experience higher mortality than males during their once-in-a-lifetime up-river spawning migration, particularly when exposed to secondary stressors (e.g. high temperatures). However, the underlying mechanisms remain unknown. One hypothesis is that female Pacific salmon hearts are more oxygen-limited than those of males and are less able to supply oxygen to the body's tissues during this demanding migration. Notably, female hearts have higher coronary blood flow, which could indicate a greater reliance on this oxygen source. Oxygen limitations can develop from naturally occurring coronary blockages (i.e. coronary arteriosclerosis) found in mature salmon hearts. If female hearts rely more heavily on coronary blood flow but experience similar arteriosclerosis levels as males, they will have disproportionately impaired aerobic performance. To test this hypothesis, we measured resting (RMR) and maximum metabolic rate (MMR), aerobic scope (AS) and acute upper thermal tolerance in coho salmon (Oncorhynchus kisutch) with an intact or artificially blocked coronary oxygen supply. We also assessed venous blood oxygen and chemistry (cortisol, ions and metabolite concentrations) at different time intervals during recovery from exhaustive exercise. We found that coronary blockage impaired MMR, AS and the partial pressure of oxygen in venous blood (PvO2) during exercise recovery but did not differ between sexes. Coronary ligation lowered acute upper thermal tolerance by 1.1°C. Although we did not find evidence of enhanced female reliance on coronary supply, our findings highlight the importance of coronary blood supply for mature wild salmon, where migration success may be linked to cardiac performance, particularly during warm water conditions., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: Continuous intracoronary thermodilution with saline allows for the accurate measurement of volumetric blood flow (Q) and absolute microvascular resistance (R μ ). However, this requires repositioning of the temperature sensor by the operator to measure the entry temperature of the saline infusate, denoted as T i ., Aims: We evaluated whether Ti could be predicted based on known parameters without compromising the accuracy of calculated Q. This would significantly simplify the technique and render it completely operator independent., Methods: In a derivation cohort of 371 patients with Q measured both at rest and during hyperaemia, multivariate linear regression was used to derive an equation for the prediction of T i . Agreement between standard Q (calculated with measured T i ) and simplified Q (calculated with predicted T i ) was assessed in a validation cohort of 120 patients that underwent repeat Q measurements. The accuracy of simplified Q was assessed in a second validation cohort of 23 patients with [ 15 O]H 2 O positron emission tomography (PET)-derived Q measurements., Results: Simplified Q exhibited strong agreement with standard Q (r=0.94, confidence interval [CI]: 0.93-0.95; intraclass correlation coefficient [ICC] 0.94, CI: 0.92-0.95; both p<0.001). Simplified Q exhibited excellent agreement with PET-derived Q (r=0.86, CI: 0.75-0.92; ICC=0.84, CI: 0.72-0.91; both p<0.001). Compared with standard Q, there were no statistically significant differences between correlation coefficients (p=0.29) or standard deviations of absolute differences with PET-derived Q (p=0.85)., Conclusions: Predicting T i resulted in an excellent agreement with measured T i for the assessment of coronary blood flow. It significantly simplifies continuous intracoronary thermodilution and renders absolute coronary flow measurements completely operator independent.

Background: Severe aortic stenosis (AS) is associated with left ventricular (LV) remodelling, likely causing alterations in coronary blood flow and microvascular resistance., Aims: We aimed to evaluate changes in absolute coronary flow and microvascular resistance in patients with AS undergoing transcatheter aortic valve implantation (TAVI)., Methods: Consecutive patients with AS undergoing TAVI with non-obstructive coronary artery disease in the left anterior descending artery (LAD) were included. Absolute coronary flow (Q) and microvascular resistance (R μ ) were measured in the LAD using continuous intracoronary thermodilution at rest and during hyperaemia before and after TAVI, and at 6-month follow-up. Total myocardial mass and LAD-specific mass were quantified by echocardiography and cardiac computed tomography. Regional myocardial perfusion (Q N ) was calculated by dividing absolute flow by the subtended myocardial mass., Results: In 51 patients, Q and R were measured at rest and during hyperaemia before and after TAVI; in 20 (39%) patients, measurements were also obtained 6 months after TAVI. No changes occurred in resting and hyperaemic flow and resistance before and after TAVI nor after 6 months. However, at 6-month follow-up, a notable reverse LV remodelling resulted in a significant increase in hyperaemic perfusion (Q N,hyper : 0.86 [interquartile range {IQR} 0.691.06] vs 1.20 [IQR 0.99-1.32] mL/min/g; p=0.008; pre-TAVI and follow-up, respectively) but not in resting perfusion (Q N,rest : 0.34 [IQR 0.30-0.48] vs 0.47 [IQR 0.36-0.67] mL/min/g; p=0.06)., Conclusions: Immediately after TAVI, no changes occurred in absolute coronary flow or coronary flow reserve. Over time, the remodelling of the left ventricle is associated with increased hyperaemic perfusion.

Background: Intracoronary continuous thermodilution is a novel technique to quantify absolute true coronary flow and microvascular resistance. However, few data are available in patients with angina with non-obstructive coronary arteries (ANOCA)., Aims: This study aimed to investigate the diagnostic potential of hyperaemic absolute coronary flow (Qmax) and absolute microvascular resistance (Rμ,hyper) among different ANOCA endotypes, and to determine the correlation between continuous - and bolus - thermodilution indexes., Methods: A total of 222 patients were scheduled for clinically indicated coronary function testing (CFT), of whom 120 patients were included in this analysis. These patients underwent CFT including acetylcholine (ACh) provocation testing and microvascular function assessment using both bolus and continuous thermodilution., Results: CFT was negative (CFT-) in 32 (26.7%) patients. Endothelium-dependent dysfunction (ACh+) was present in 63 (52.5%) patients, and coronary microvascular dysfunction (CMD) identified at bolus thermodilution (CMD+) was present in 62 (51.7%) patients. Patients with a positive CFT (CFT+) showed significantly lower Qmax and higher Rμ,hyper values as compared to CFT-. Qmax was significantly lower in CMD+ versus CMD- patients (0.174 vs 0.222 L/min; p=0.04) but did not differ in patients with or without a positive ACh test (0.198 vs 0.219 L/min; p=0.86)., Conclusions: The prevalence of a CFT+ is high in a selected ANOCA population. In our study, Qmax and Rμ,hyper were associated with a positive CFT. Qmax was associated with the presence of microvascular dysfunction but not with a positive acetylcholine test. The novel continuous thermodilution method can provide further insights into ANOCA endotypes.

Background: Despite patients with successful revascularization as evidenced by angiographic findings, inadequate clinical management of coronary microcirculatory dysfunction (CMD) may result in preventable adverse outcomes. Therefore, it is imperative to use a multimodal data‑driven predictive model for the occurrence of CMD in patients with acute myocardial infarction (AMI) following emergency percutaneous coronary intervention (PCI)., Methods: A prospective case-control analysis was conducted on a cohort of 77 patients with AMI who underwent PCI. The most informative predictors were selected for the predictive model through the application of LASSO analysis and multi-factor logistic regression. The diagnosis of CMD is based on findings from cardiac magnetic resonance (CMR)., Results: Based on the findings from LASSO analysis and multi-factor logistic regression, variables including sex, neutrophil-to-lymphocyte ratio (NLR), Gensini score, and diabetes mellitus were identified as independent predictors for the development of CMD in AMI patients who underwent emergency PCI. The predictive model was evaluated using bootstrap self-sampling 500 times. The resulting predictive model demonstrated an AUC value of 0.897 (95% CI: 0.827-0.958). The calibration curves exhibited good concordance between the predictions generated by the model and the CMR analysis. Furthermore, decision curve analysis revealed that the predictive model provided valuable clinical benefit in predicting CMD., Conclusions: The multivariate predictive model, constructed using readily available clinical variables in patients with AMI who underwent PCI, demonstrates satisfactory predictability for identifying comorbid CMD, thereby facilitating the identification of high-risk patients., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid-structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease. However, the clinical application of these techniques has been limited to hemodynamic assessment of coronary disease severity, with the potential to refine the assessment and management of coronary disease. Improved computational efficiency and large clinical trials are required to provide an incremental clinical benefit of these techniques beyond existing tools. This contemporary review is a clinically relevant overview of the disturbed coronary flow and its associated pathological consequences. The contemporary methods to assess disturbed flow are reviewed, including clinical applications of these techniques. Current limitations and future opportunities in the field are also discussed.

Background: Approximately 50% of women referred for invasive coronary angiography have angina and nonobstructive coronary arteries, which includes coronary microvascular dysfunction, vasospastic angina, and other vasomotor disorders. We sought to determine the real-world diagnostic yield of invasive coronary angiography and coronary function testing in women with angina and nonobstructive coronary arteries., Methods and Results: From 2018 to 2023, we enrolled 198 women who underwent either coronary angiography (CA) alone (n=99) or coronary function testing (CFT; n=99). Mean±SD age was 62±10 years (CA alone) compared with 57±10 years (CFT). Coronary angiography was interpreted as nonobstructive coronary artery disease more frequently after CA alone (79% versus 52%). Of the women who underwent CFT, 82% (N=81) were found to have vasomotor disorders, including coronary microvascular dysfunction (27%), vasospastic angina (32%), mixed coronary microvascular dysfunction/vasospastic angina (16%), endothelial dysfunction (10%; without spasm), elevated resting flow (2%), or symptomatic myocardial bridging (4%). Compared with women undergoing CA alone, medications were changed more frequently after CFT at 24 hours (41% versus 65%; P =0.001) and between 24 hours and 30 days (30% versus 44%; P =0.04) with intensification of antianginal therapy (79% versus 92%; P< 0.0001) and increased use of calcium channel blockers (36% versus 63%; P< 0.0001)., Conclusions: Our findings demonstrate that women presenting with suspected ischemic heart disease undergoing CA alone only received an anatomic diagnosis, whereas >80% of women undergoing CFT received a specific diagnosis of a coronary vasomotor disorder and greater intensification of antianginal therapy.

Background: We aimed to develop a framework for generating three-dimensional (3D) myocardial blood flow (MBF) images, computing their accuracy against clinically validated two-dimensional (2D) polar MBF maps of the left ventricle, and evaluating their improvements in image quality over relative myocardial perfusion imaging (MPI)., Methods: N = 40 patients with a wide range of defect severities and uptake dynamics were retrospectively studied. The FlowQuant™ software was used to generate reference MPI and polar MBF maps and was adapted for voxel-wise MBF mapping. We evaluated agreement between parametric vs polar values for MBF at rest and stress and for reserve (stress/rest MBF). We also assessed improvements in image quality, assessed by signal-to-noise ratio, contrast-to-noise ratio, tissue-to-blood ratio, and defect severity, from relative MPI to MBF., Results: There was excellent agreement between 3D parametric and 2D polar maps for all flow parameters (interclass correlation coefficient >0.96), albeit with minimal bias (<8%) for rest and stress MBF at the patient level. Image quality substantially improved from MPI to MBF in every patient for all image-quality metrics (P < 0.0001) CONCLUSIONS: We developed a robust methodology for producing highly accurate 3D MBF images exhibiting considerably improved image quality compared to relative MPI commonly used in clinical practice., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood flow (CBF) in response to myocardial oxygen demand. This perfusion mismatch causes myocardial ischemia, which manifests in patients as microvascular angina (MVA). CMD can be diagnosed non-invasively via multiple imaging techniques or invasively using coronary function testing (CFT), which assists in determining the specific mechanisms involving endothelium-independent and dependent epicardial and microcirculation domains. Unlike traditional coronary artery disease (CAD), CMD can often occur in patients without obstructive atherosclerotic epicardial disease, which can make the diagnosis of CMD difficult. Moreover, MVA due to CMD is more prevalent in women and carries increased risk of future cardiovascular events. Successful treatment of symptomatic CMD is often patient-specific risk factor and endotype targeted. This article aims to review newly identified mechanisms and novel treatment strategies for managing CMD, and outline sex-specific differences in the presentation and pathophysiology of the disease., Competing Interests: The authors declare there are no competing interests.

Background: Arterial spin labeling (ASL) allows non-invasive quantification of myocardial blood flow (MBF). Double-ECG gating (DG) ASL is more robust to heart rate variability than single-ECG gating (SG), but its reproducibility requires further investigation. Moreover, the existence of multiple quantification models hinders its application. Frequency-offset-corrected-inversion (FOCI) pulses provide sharper edge profiles than hyperbolic-secant (HS), which could benefit myocardial ASL., Purpose: To assess the performance of MBF quantification models for DG compared to SG ASL, to evaluate their reproducibility and to compare the effects of HS and FOCI pulses., Study Type: Prospective., Subjects: Sixteen subjects (27 ± 8 years)., Field Strength/sequence: 1.5 T/DG and SG flow-sensitive alternating inversion recovery ASL., Assessment: Three models for DG MBF quantification were compared using Monte Carlo simulations and in vivo experiments. Two models used a fitting approach (one using only a single label and control image pair per fit, the other using all available image pairs), while the third model used a T1 correction approach. Slice profile simulations were conducted for HS and FOCI pulses with varying B0 and B1. Temporal signal-to-noise ratio (tSNR) was computed for different acquisition/quantification strategies and inversion pulses. The number of images that minimized MBF error was investigated in the model with highest tSNR. Intra and intersession reproducibility were assessed in 10 subjects., Statistical Tests: Within-subject coefficient of variation, analysis of variance. P-value <0.05 was considered significant., Results: MBF was not different across acquisition/quantification strategies (P = 0.27) nor pulses (P = 0.9). DG MBF quantification models exhibited significantly higher tSNR and superior reproducibility, particularly for the fitting model using multiple images (tSNR was 3.46 ± 2.18 in vivo and 3.32 ± 1.16 in simulations, respectively; wsCV = 16%). Reducing the number of ASL pairs to 13/15 did not increase MBF error (minimum = 0.22 mL/g/min)., Data Conclusion: Reproducibility of MBF was better for DG than SG acquisitions, especially when employing a fitting model., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 1., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: Non-invasive computation of the index of microcirculatory resistance from coronary computed tomography angiography (CTA), referred to as IMR[Formula: see text], is a promising approach for quantitative assessment of coronary microvascular dysfunction (CMD). However, the computation of IMR[Formula: see text] remains an important unresolved problem due to its high requirement for the accuracy of coronary blood flow. Existing CTA-based methods for estimating coronary blood flow rely on physiological assumption models to indirectly identify, which leads to inadequate personalization of total and vessel-specific flow., Methods: To overcome this challenge, we propose a vascular deformation-based flow estimation (VDFE) model to directly estimate coronary blood flow for reliable IMR[Formula: see text] computation. Specifically, we extract the vascular deformation of each vascular segment from multi-phase CTA. The concept of inverse problem solving is applied to implicitly derive coronary blood flow based on the physical constraint relationship between blood flow and vascular deformation. The vascular deformation constraints imposed on each segment within the vascular structure ensure sufficient individualization of coronary blood flow., Results: Experimental studies on 106 vessels collected from 89 subjects demonstrate the validity of our VDFE, achieving an IMR[Formula: see text] accuracy of 82.08 %. The coronary blood flow estimated by VDFE has better reliability than the other four existing methods., Conclusion: Our proposed VDFE is an effective approach to non-invasively compute IMR[Formula: see text] with excellent diagnostic performance., Significance: The VDFE has the potential to serve as a safe, effective, and cost-effective clinical tool for guiding CMD clinical treatment and assessing prognosis.

Dyslipidemia is an important risk factor for cardiovascular morbidity and mortality. Although low-density lipoprotein (LDL) is primarily responsible, the importance of triglyceride (TG) and high-density lipoprotein (HDL) has also been recognized. The present study investigated the effect of the atherogenic index of plasma (AIP), in which atherogenic and protective lipoproteins were evaluated together, on the initial flow in patients with ST elevation myocardial infarction. AIP was calculated as log(TG/HDL-cholesterol). Patients included in the study (n = 1535) were divided into Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 and >0. AIP was found to be significantly different between 2 groups (.55 ± .23 vs .67 ± .21; P < .001). AIP was an independent predictor for pre-intervention TIMI flow (Odds Ratio: 2.778). A moderate correlation was found between TIMI frame count measurements, calculated in patients with TIMI 2-3, and AIP (Pearson correlation coefficient: .63, P < .001). In the receiver operating characteristic analysis, AIP showed the highest area under curve (AUC) compared with other lipid parameters for predicting vascular patency. The AUC of AIP was .634, the cut-off value was .59, and the sensitivity and specificity were 67.6% and 68.4%, respectively ( P < .001). In conclusion, AIP was found to be an important marker affecting pre-percutaneous coronary intervention TIMI flow., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: This study aimed to assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared with a rest-stress protocol using 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) and to gain insights into the time dependency of such effects., Methods and Results: Quantitative MBF at rest (rMBF) and during adenosine-induced stress (sMBF) and myocardial flow reserve (MFR) were obtained from 331 retrospectively identified patients who underwent 13N-ammonia PET MPI for suspected chronic coronary syndrome and who all exhibited no perfusion defects. Of these, 146 (44.1%) underwent a rapid stress-rest protocol with a time interval (Δtstress-rest) of 20 ± 4 min between adenosine infusion offset and rest imaging, as per clinical routine. The remaining 185 (55.9%) patients underwent a rest-stress protocol and served as the reference. Groups did not differ regarding demographics, risk factors, medication, left ventricular function, and calcium scores. rMBF was significantly higher in the stress-rest vs. the rest-stress group [0.80 (interquartile range 0.66-1.00) vs. 0.70 (0.58-0.83) mL·min-1·g-1, P < 0.001], and, as sMBF was identical between groups [2.52 (2.20-2.96) vs. 2.50 (1.96-3.11), P = 0.347], MFR was significantly lower in the stress-rest group [3.07 (2.43-3.88) vs. 3.50 (2.63-4.10), P = 0.007]. There was a weak correlation between Δtstress-rest and rMBF (r = -0.259, P = 0.002) and between Δtstress-rest and MFR (r = 0.163, P = 0.049), and the proportion of patients with abnormally high rMBF was significantly decreasing with increasing Δtstress-rest., Conclusion: Intravenously applied adenosine induces a long-lasting hyperaemic effect on the myocardium. Consequently, rapid stress-rest protocols could lead to an overestimation of rMBF and an underestimation of MFR., Competing Interests: Conflict of interest: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Microvascular obstruction (MVO) measured by cardiac magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) has important prognostic implications. While invasive index of microvascular resistance (IMR) have been shown to predict the occurrence and extent of MVO, the role of the angiography-based microvascular resistance (Angio-IMR) for this purpose remains unknown. The present study aims to perform a head-to-head comparison of wire-based and angiography-derived microcirculatory resistance (IMR and Angio-IMR, respectively) for the detection of MVO., Methods: Patients with a first STEMI and multivessel disease underwent CMR for detection of MVO, and angio-IMR and IMR measurements during PPCI and at 30 day follow up, both in STEMI culprit and non-culprit vessels., Results: 58 patients were included (mean age 60.7 ± 9.9 years, 82% male). At the time of PPCI, angio-IMR and IMR exhibited significant correlation (r = 0.70, P < 0.001), and agreement (coefficient of agreement 0.58). Both indices showed good predictive value of MVO [Angio IMR: AUC 0.79 (95% CI: 0.667-0.928); IMR: AUC 0.70 (95% CI: 0.539-0.853); p = 0.15]. Angio-IMR 40 U and IMR 34 U were identified as best cut-offs for prediction of MVO. In non-culprit vessels, angio-IMR and IMR also correlated well (rho = 0.59, p < 0.001), with overall lower mean values compared to culprit vessels (Angio-IMR: 36 vs. 23; IMR: 39 vs. 22, p < 0.001 for both comparisons)., Conclusion: Angio-IMR constitutes a valid alternative to wire-based IMR in predicting MVO in STEMI. Angio-IMR and IMR show a good correlation in the acute and subacute STEMI phases, both in culprit and non-culprit vessels., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the global population. Both, coronary artery disease and NAFLD are linked to underlying insulin resistance and inflammation as drivers of the disease. Coronary flow reserve parameters, including coronary flow reserve velocity (CFRV), baseline diastolic peak flow velocity (DPFV), and hyperemic DPFV, are noninvasive markers of coronary microvascular circulation. The existing literature contains conflicting findings regarding these parameters in NAFLD patients., Methods: A comprehensive systematic search was conducted on major electronic databases from inception until May 8, 2024, to identify relevant studies. We pooled the standardized mean differences (SMD) with 95% confidence intervals (CI) using the inverse-variance random-effects model. Statistical significance was set at P < .05., Results: Four studies with 1139 participants (226 with NAFLD and 913 as controls) were included. NAFLD was associated with a significantly lower CFRV (SMD: -0.77; 95% CI: -1.19, -0.36; P < .0002) and hyperemic DPFV (SMD: -0.73; 95% CI: -1.03, -0.44; P < .00001) than the controls. NAFLD demonstrated a statistically insignificant trend toward a reduction in baseline DPFV (SMD: -0.09; 95% CI: -0.38, 0.19; P = .52) compared to healthy controls., Conclusion: Patients with NAFLD are at a higher risk of coronary microvascular dysfunction, as demonstrated by reduced CFRV and hyperemic DPFV. The presence of abnormal coronary flow reserve in patients with NAFLD provides insights into the higher rates of cardiovascular disease in these patients. Early aggressive targeted interventions for impaired coronary flow reserve in subjects with NAFLD may lead to improvement in clinical outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cardiovascular disease is the predominant cause of mortality on a global scale. Research indicates that women exhibit a greater likelihood of presenting with non-obstructive coronary artery disease (CAD) when experiencing symptoms of myocardial ischemia in comparison to men. Additionally, women tend to experience a higher burden of symptoms relative to men, and despite the presence of ischemic heart disease, they are frequently reassured erroneously due to the absence of obstructive CAD. In cases of ischemic heart disease accompanied by symptoms of myocardial ischemia but lacking obstructive CAD, it is imperative to consider coronary microvascular dysfunction as a potential underlying cause. Coronary microvascular dysfunction, characterized by impaired coronary flow reserve resulting from functional and/or structural abnormalities in the microcirculation, is linked to adverse cardiovascular outcomes. Lifestyle modifications and the use of anti-atherosclerotic and anti-anginal medications may offer potential benefits, although further clinical trials are necessary to inform treatment strategies. This review aims to explore the prevalence, underlying mechanisms, diagnostic approaches, and therapeutic interventions for coronary microvascular dysfunction.

Objective: Coronary artery disease (CAD) is frequent, but coronary slow flow (CSF) is a less common cardiovascular disease with a significant risk of mortality and morbidity. Endocan is a proinflammatory glycopeptide that has been investigated in cardiovascular diseases as well as some inflammatory diseases in recent years. We planned to compare the levels of endocan in both CAD and CSF in a similar population and examine the relationship of endocan with additional clinical variables., Materials and Methods: In the trial, we included 169 consecutive subjects having a coronary angiography indication. According to the results of coronary angiography, 58 people were included in the CAD group, 52 were in the CSF group, and 59 people were in the control group. The control group includes those who did not have any lesions in their epicardial coronary arteries. Thrombolysis in myocardial infarction (TIMI)-frame counts (TFC) were calculated for all patients., Results: Notably, 2.6% of the population in our study had CSF. Both the CAD (555±223 pg/mL) and CSF (559±234 pg/mL) groups had higher endocan levels than the control group (331±252 pg/mL) (p<0.001). There were similar endocan levels between the CAD and CSF groups. Endocan levels were shown to be favorably associated with mean TFC (r=0.267; p0.001). Serum endocan levels (particularly those above 450 pg/mL) and the presence of hyperlipidemia were the most important predictors of both CAD and CSF., Conclusion: Endocan levels are higher in CAD and CSF patients than in those with normal coronary arteries.

Background: Limited data exist on the role of coronary collaterals circulation (CCC) in patients with ST-elevation acute coronary syndrome (STE-ACS). This study aimed to assess CCC and the in-hospital course of patients with CCC undergoing primary percutaneous coronary intervention (pPCI)., Methods: The study included consecutive STE-ACS patients undergoing pPCI. Good CCC was defined as Rentrop collateral score (RCS) of 2-3. Patients with good and poor CCC were compared regarding clinical characteristics, angiographic patterns, and hospital course., Results: In the sample of 4683 patients, mean age was 55.6 ± 11 years, and 78.8 % were male. Good CCC was observed in 499 (10.7 %) patients. The rate of intra-procedure slow-flow/no-reflow (SF/NR) was 29.9 % vs. 20.5 % (p < 0.001), and the rate of composite adverse clinical outcomes (CACO) was 21.2 % vs. 19 % (p = 0.225) for patients with good and poor CCC, respectively. Multivariable analysis identified left ventricular end-diastolic pressure (LVEDP), multi-vessel disease (MVD), and thrombus grade ≥4 as independent predictors of good CCC, with adjusted odds ratios of 0.98 [0.97-0.99], 1.69 [1.35-2.10], and 3.45 [2.64-4.52], respectively. In propensity-matched cohorts, the intra-procedure SF/NR rate was 29.9 % vs. 26.9 % (p = 0.292), and the rate of CACO was 21.2 % vs. 23.4 % (p = 0.403) for patients with good and poor CCC, respectively., Conclusion: Angiographic evidence of good CCC in STE-ACS patients was limited. Good CCC was associated with a higher prevalence of MVD, high thrombus burden, and low pre-procedure LVEDP, resulting in a higher incidence of intra-procedure SF/NR. However, the CACO did not differ significantly between patients with good and poor CCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier, a division of RELX India, Pvt. Ltd.)

Approximately half of all coronary angiograms performed for angina do not show obstructive coronary artery disease, and many of these patients have coronary microvascular dysfunction (CMD). Invasive testing for CMD has increased with the advent and wider availability of thermodilution systems. We review CMD pathophysiology and invasive diagnostic testing using the Doppler and thermodilution systems. We report the results of a PubMed search of invasive microvascular testing and discuss limitations of current diagnostic algorithms in the diagnosis of CMD, including controversies regarding the optimal cutoff value for abnormal coronary flow reserve, use of microvascular resistance indices, and options for increasing sensitivity of testing., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure., Background: More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear., Methods: The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of 2 treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for 6 months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total., Conclusions: This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954., Competing Interests: Conflict of interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown., Methods: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin., Results: Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P <0.03) but attenuated, relative to controls (4.80±0.63; P =0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort ( P <0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P <0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P <0.05, all comparisons)., Conclusions: Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis., Competing Interests: None.

Objective: Major challenges for clinical applications of in silico medicine are limitations in time and computational resources. Computational approaches should therefore be tailored to specific applications with relatively low complexity and must be verified and validated against clinical gold standards., Methods: This study performed computational fluid dynamics simulations of left ventricular hemodynamics of different complexity based on shape reconstruction from steady state gradient echo magnetic resonance imaging (MRI) data. Computed flow results of a rigid wall model (RWM) and a prescribed motion fluid-structure interaction (PM-FSI) model were compared against phase-contrast MRI measurements for three healthy subjects., Results: Extracted boundary conditions from the steady state MRI sequences as well as computed metrics, such as flow rate, valve velocities, and kinetic energy show good agreement with in vivo flow measurements. Regional flow analysis reveals larger differences., Conclusion: Basic flow structures are well captured with RWM and PM-FSI. For the computation of further biomarkers like washout or flow efficiency, usage of PM-FSI is required. Regarding boundary-near flow, more accurate anatomical models are inevitable., Significance: These results delineate areas of application of both methods and lay a foundation for larger validation studies and sensitivity analysis for healthy and diseased cases, being an essential step upon clinical translations.

Studies assessing the treatment of refractory no-reflow in patients with ST-elevation myocardial infarction (STEMI) are limited to clinical cases and pilot studies. This study aimed to evaluate the efficacy and safety of intracoronary adrenaline administration in such patients. Ninety consecutive patients with refractory coronary no-reflow during percutaneous coronary intervention (PCI) were prospectively included after the initial failure of conventional treatment. They were randomized into 2 groups: 45 patients in Group 1 received adrenaline, and 45 patients in Group 2 (control) received conventional treatments alone. After intracoronary drug administration, the adrenaline group demonstrated significantly higher rates of coronary flow restoration in the infarct-related artery to the level of thrombolysis in myocardial infarction grade 3 (56% vs 29% [p = 0.01]) and resolution of STEMI >50% after PCI (78% vs 36% [p <0.001]). Additionally, the adrenaline group showed a lower indexed microvascular obstruction (MVO) volume compared with the control group (0.9 [0.3; 3.1] % vs 1.9 [0.6; 7.9] % [p = 0.048]). A significant improvement in ejection fraction (EF) was observed in the adrenaline group (p = 0.025). Intracoronary adrenaline administration during PCI in patients with STEMI with refractory no-reflow is more effective compared with conventional treatments. This approach improves coronary flow in the infarct-related artery, facilitates a faster resolution of STEMI, enhances EF, and reduces MVO volume. Intracoronary adrenaline administration demonstrates a comparable safety profile to conventional treatment strategies in terms of life-threatening arrhythmias occurrence. The study suggests that intracoronary adrenaline administration during PCI could be an effective treatment strategy for patients with STEMI with refractory no-reflow., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dysfunction of the coronary microvasculature has become increasingly recognized as an important mechanism of myocardial ischemia in patients without obstructive coronary artery disease. The causes and management of coronary microvascular dysfunction remain poorly understood and are still largely based on extrapolation of epicardial coronary artery disease data. Quantification of myocardial blood flow and flow reserve have improved diagnosis, though important questions remain. In this review, we explain current understanding of the spectrum of pathophysiology of coronary microvascular dysfunction, summarize current diagnostic techniques to assess for coronary microvascular dysfunction, and appraise the limited data on management options specifically for patients with coronary microvascular dysfunction., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: We evaluated the prevalence and outcomes of competitive flow in the terminal right coronary artery (RCA) graft after coronary artery bypass grafting (CABG) with left internal thoracic artery-based Y-composite grafting at 1 year after CABG., Methods: We enrolled 642 patients who underwent Y-composite graft-based off-pump CABG with in situ left internal thoracic artery between 2014 and 2022. All patients underwent early postoperative angiography, and 1-year postoperative angiography was performed in 81.2% (522/642) of patients., Results: The early occlusion rate of distal anastomoses with Y-composite graft was 2.1%. Competitive flow was observed in 69 of 642 anastomoses (10.7%). Multivariate analysis showed that the maximal degree of target vessel stenosis (odds ratio [OR], 0.909; 95% CI, 0.886-0.931; P < .001), maximal degree of non-terminal target vessel in Y-arm grafts (OR, 1.103; 95% CI, 1.047-1.172; P < .001), and diabetes mellitus (OR, 0.535; 95% CI, 0.303-0.934; P = .029) were factors associated with competitive flow to the RCA territory. The optimal cutoff value for the degree of terminal target vessel stenosis predicting competitive flow to the RCA territory was 92.5%. The 1-year graft failure rate of anastomoses with competitive flow of the terminal anastomosis was 30.9% (17/55). The presence of competitive flow on early angiography was the only factor associated with graft occlusion of the terminal anastomosis at 1 year (OR, 2.339; 95% CI, 1.165-4.481; P = .013)., Conclusions: For terminal anastomosis to the RCA territory in Y-composite graft-based CABG, the presence of competitive flow on early angiography was associated with graft occlusion of the terminal anastomosis at 1 year. Notably, 30.9% of these grafts demonstrated failure on 1-year follow-up angiography., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to elucidate the association between serum levels of circular RNAs circ&#95;0001879 and circ&#95;0004104 and the occurrence of coronary microcirculation disorders along with post-PCI prognosis in individuals with stable coronary heart disease., Methods: A cohort of 92 patients diagnosed with stable coronary heart disease and subjected to PCI between June 2020 and June 2022 at our institution was assembled. Patients were categorized into an exposed group (n = 60) and a non-exposed group (n = 32), predicated on the coronary angiography-derived microcirculation resistance index (caIMR)., Results: Comparative analysis revealed significantly elevated levels of circ&#95;0001879 and circ&#95;0004104 in the serum of the exposed group compared to the non-exposed group, with statistical significance (P < 0.05). Post-PCI, both caFFR and caIMR values demonstrated a marked increase in comparison to pre-surgical measurements within both groups, with the exposed group exhibiting lower indices post-surgery relative to the non-exposed group, indicative of superior microcirculatory outcomes (P < 0.05). Furthermore, serum levels of circ&#95;0001879 and circ&#95;0004104 were inversely correlated with favorable prognosis, with lower levels observed in patients with positive outcomes (P < 0.05). The predictive accuracy for poor prognosis, as indicated by the area under the curve (AUC), was enhanced when circ&#95;0001879 and circ&#95;0004104 were considered in tandem (AUC = 0.934), surpassing the predictive power of individual assessments (Z combination vs circ&#95;0001879 = 2.439, Z combination vs circ&#95;0004104 = 2.317, P < 0.05)., Conclusion: Elevated serum levels of circ&#95;0001879 and circ&#95;0004104 are observed in stable coronary heart disease patients and are significantly associated with the presence of coronary microcirculation disorders and post-PCI prognosis, underscoring their potential as prognostic biomarkers., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: Invasive fractional flow reserve (FFR) measurement is the gold standard method for coronary artery disease (CAD) diagnosis. FFR-CT exploits computational fluid dynamics (CFD) for non-invasive evaluation of FFR, simulating coronary flow in virtual geometries reconstructed from computed tomography (CT), but suffers from cost-intensive computing process and uncertainties in the definition of patient specific boundary conditions (BCs). In this work, we investigated the use of time-averaged steady BCs, compared to pulsatile to reduce the computational time and deployed a self-adjusting method for the tuning of BCs to patient-specific clinical data., Methods: 133 coronary arteries were reconstructed form CT images of patients suffering from CAD. For each vessel, invasive FFR was measured. After segmentation, the geometries were prepared for CFD simulation by clipping the outlets and discretizing into tetrahedral mesh. Steady BCs were defined in two steps: (i) rest BCs were extrapolated from clinical and image-derived data; (ii) hyperemic BCs were computed from resting conditions. Flow rate was iteratively adjusted during the simulation, until patient's aortic pressure was matched. Pulsatile BCs were defined exploiting the convergence values of steady BCs. After CFD simulation, lesion-specific hemodynamic indexes were computed and compared between group of patients for which surgery was indicated and not. The whole pipeline was implemented as a straightforward process, in which each single step is performed automatically., Results: Steady and pulsatile FFR-CT yielded a strong correlation (r = 0.988, p < 0.001) and correlated with invasive FFR (r = 0.797, p < 0.001). The per-point difference between the pressure and FFR-CT field predicted by the two methods was below 1 % and 2 %, respectively. Both approaches exhibited a good diagnostic performance: accuracy was 0.860 and 0.864, the AUC was 0.923 and 0.912, for steady and pulsatile case, respectively. The computational time required by steady BCs CFD was approximatively 30-folds lower than pulsatile case., Conclusions: This work shows the feasibility of using steady BCs CFD for computing the FFR-CT in coronary arteries, as well as its computational and diagnostic performance within a fully automated pipeline., Competing Interests: Declaration of competing interest All authors disclose that they have no conflict of interest, no financial arrangement with products figuring in the submitted manuscript or with a company making a competing product. All those who fulfil the criteria for authorship have been included as authors and each author contributed significantly to the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Accurate modeling of blood dynamics in the coronary microcirculation is a crucial step toward the clinical application of in silico methods for the diagnosis of coronary artery disease. In this work, we present a new mathematical model of microcirculatory hemodynamics accounting for microvasculature compliance and cardiac contraction; we also present its application to a full simulation of hyperemic coronary blood flow and 3D myocardial perfusion in real clinical cases. Microvasculature hemodynamics is modeled with a compliant multi-compartment Darcy formulation, with the new compliance terms depending on the local intramyocardial pressure generated by cardiac contraction. Nonlinear analytical relationships for vessels distensibility are included based on experimental data, and all the parameters of the model are reformulated based on histologically relevant quantities, allowing a deeper model personalization. Phasic flow patterns of high arterial inflow in diastole and venous outflow in systole are obtained, with flow waveforms morphology and pressure distribution along the microcirculation reproduced in accordance with experimental and in vivo measures. Phasic diameter change for arterioles and capillaries is also obtained with relevant differences depending on the depth location. Coronary blood dynamics exhibits a disturbed flow at the systolic onset, while the obtained 3D perfusion maps reproduce the systolic impediment effect and show relevant regional and transmural heterogeneities in myocardial blood flow (MBF). The proposed model successfully reproduces microvasculature hemodynamics over the whole heartbeat and along the entire intramural vessels. Quantification of phasic flow patterns, diameter changes, regional and transmural heterogeneities in MBF represent key steps ahead in the direction of the predictive simulation of cardiac perfusion., (© 2024. The Author(s).)

Background: Whether saline-induced hyperaemia captures exercise-induced coronary flow regulation remains unknown., Aims: Through this study, we aimed to describe absolute coronary flow (Q) and microvascular resistance (Rμ) adaptation during exercise in participants with angina with non-obstructive coronary artery disease (ANOCA) and to explore the correlations between saline- and exercise-derived coronary flow reserve (CFR) and microvascular resistance reserve (MRR)., Methods: Rμ, Q, CFR and MRR were assessed in the left anterior descending artery using continuous thermodilution with saline infusion at 10 mL/min (rest), 20 mL/min (hyperaemia) and finally at a 10 mL/min infusion rate during stress testing with a dedicated supine cycling ergometer. An incremental workload of 30 watts every two minutes was applied. A saline-derived CFR (CFR saline ) cutoff <2.5 was used to identify coronary microvascular dysfunction (CMD)., Results: CFR saline -defined CMD was observed in 53.3% of the participants (16/30). While cycling, these patients less of an ability to increase Q (7 [interquartile range [IQR] 30.5-103.0] vs 21 [IQR 5.8-45.0] mL/min/30 watts; p=0.01) due to a smaller decrease of Rμ (109 {IQR 32-286} vs 202 [IQR 102-379] Wood units [WU]/30 watts; p<0.01) as compared with the group with normal CFR saline . In the overall population, CFR saline and exercise-derived CFR (CFR exercise ) were 2.70±0.90 and 2.85±1.54, respectively, with an agreement classification of 83.3%. A good correlation between saline and exercise techniques for both CFR (r=0.73; p<0.0001) and MRR (r=0.76; p<0.0001) was observed. Among participants with normal CFR saline , 28.7% (4/14) had an impaired CFR exercise <2.5 at the peak of exercise due to a moderate and late decrease of Rμ., Conclusions: Saline-induced hyperaemia provided a valid surrogate for exercise physiology independently of the absolute level of CFR and MRR, although exercise provided more granularity to evaluate adaptation among participants with exercise-related CMD.

Background: Despite prompt reperfusion, the risk of adverse clinical outcomes following ST-segment-elevation myocardial infarction (STEMI) remains pronounced, owing partly to suboptimal reperfusion. However, coronary functional evaluation is seldom feasible during primary percutaneous coronary intervention (PPCI). We aimed to examine the clinical implication of a simple coronary assessment based on single-angiographic view (μQFR) during PPCI in discriminating impaired coronary flow and adverse outcomes for STEMI., Methods: STEMI Patients undergoing successful PPCI were enrolled and followed up prospectively from 4 medical centers in China. Post-PPCI μQFR of culprit vessels were analyzed. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal MI, ischemia-driven target-vessel revascularization and readmission for heart failure., Results: A total of 570 patients with STEMI were enrolled, and post-PCI μQFR was analyzable in 557 (97.7%) patients, with a median of 0.94. Patients with low post-PCI μQFR showed higher incidence of adverse outcomes than those with high μQFR, showing a 2.5-fold increase in the risk for MACE (hazard ratio: 2.51, 95% confidence intervals: 1.33 to 4.72; P = 0.004). Moreover, post-PCI μQFR significantly increased discriminant ability for the occurrence of MACE when added to traditional GRACE risk score for STEMI (integrated discrimination improvement: 0.029; net reclassification index: 0.229; P < 0.05)., Conclusions: A low μQFR of culprit vessel in PPCI is independently associated with worse clinical outcomes in patients with STEMI. The single-angiographic-view-based coronary evaluation is a feasible tool for discriminating poor prognosis and could serve as a valuable complement in risk stratification for STEMI., Competing Interests: Declaration of competing interest Dr. Shengxian Tu is a consultant of Pulse Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Stress-transthoracic Doppler echocardiography (S-TDE) provides a noninvasive assessment of coronary flow parameters in the left anterior descending artery (LAD). However, the association between morphological characteristics and coronary flow changes after elective percutaneous coronary intervention (PCI) remains unclear. We aimed to evaluate the relationships between periprocedural coronary flow changes observed on S-TDE and lesion-specific plaque characteristics obtained by optical coherence tomography (OCT) in the interrogated vessels in patients with chronic coronary syndrome (CCS)., Methods and Results: Patients with CCS who underwent pre- and post-PCI S-TDE and elective fractional flow reserve (FFR)-guided PCI under OCT guidance for de novo single LAD lesions were included. S-TDE-derived hyperemic diastolic peak flow velocity (hDPV) was used as a surrogate for coronary flow. Lesions were categorized into two groups based on the %hDPV increase or decrease. The baseline clinical, physiological, and OCT findings were compared between the groups. In total, 103 LAD lesions were studied in 103 patients. After PCI, hDPV significantly increased from 55.6 cm/s to 69.5 cm/s (P<0.01), with a median %hDPV increase of 27.2 (6.32-59.1) %, while %hDPV decreased in 20 (19.4%) patients. The FFR improved in all patients. On OCT, layered plaques were more frequently present in the culprit vessels in the %hDPV-decrease group than in the %hDPV-increase group (85.0% vs. 50.6%, P = 0.01). Multivariable logistic regression analysis showed that the presence of layered plaques and high pre-PCI hDPV were independent predictors of %hDPV decrease., Conclusions: In patients who underwent successful uncomplicated elective PCI for de novo single LAD lesions, the presence of layered plaques was independently associated with hyperemic coronary flow decrease as assessed by S-TDE., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Usui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We prospectively assessed the reproducibility of a novel low-dose single-volume dynamic computed tomography (CT) myocardial blood flow measurement technique., Methods: Thirty-four pairs of measurements were made under rest and stress conditions in 13 swine (54.3 ± 12.3 kg). One or two acquisition pairs were acquired in each animal with a 10-min delay between each pair. Contrast (370 mgI/mL; 0.5 mL/kg) and a diluted contrast/saline chaser (0.5 mL/kg; 30:70 contrast/saline) were injected peripherally at 5 mL/s, followed by bolus tracking and acquisition of a single volume scan (100 kVp; 200 mA) with a 320-slice CT scanner. Bolus tracking and single volume scan data were used to derive perfusion in mL/min/g using a first-pass analysis model; the coronary perfusion territories of the left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA) were automatically assigned using a previously validated minimum-cost path technique. The reproducibility of CT myocardial perfusion measurement within the LAD, LCx, RCA, and the whole myocardium was assessed via regression analysis. The average CT dose index (CTDI) of perfusion measurement was recorded., Results: The repeated first (P myo1 ) and second (P myo2 ) single-volume CT perfusion measurements were related by P myo2 = 1.01P myo1 - 0.03(ρ = 0.96; RMSE = 0.08 mL/min/g; RMSE = 0.07 mL/min/g) for the whole myocardium, and by P reg2 = 0.86P reg1 + 0.13(ρ = 0.87; RMSE = 0.31 mL/min/g; RMSE = 0.29 mL/min/g) for the LAD, LCx, and RCA perfusion territories. The average CTDI of the single-volume CT perfusion measurement was 10.5 mGy., Conclusion: The single-volume CT blood flow measurement technique provides reproducible low-dose myocardial perfusion measurement using only bolus tracking data and a single whole-heart volume scan., Relevance Statement: The single-volume CT blood flow measurement technique is a noninvasive tool that reproducibly measures myocardial perfusion and provides coronary CT angiograms, allowing for simultaneous anatomic-physiologic assessment of myocardial ischemia., Key Points: A low-dose single-volume dynamic CT myocardial blood flow measurement technique is reproducible. Motion misregistration artifacts are eliminated using a single-volume CT perfusion technique. This technique enables combined anatomic-physiologic assessment of coronary artery disease., (© 2024. The Author(s).)

Background: Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR., Objectives: This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial., Methods: Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m 2 ) [95% CI: 26.1-29.5 kg/m 2 )]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31 phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments., Results: Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009)., Conclusions: Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939)., Competing Interests: Funding Support and Author Disclosures The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the Department of Health and Social Care. This independent research has been jointly funded by the Wellcome Trust (grant number: 221690/Z/20/Z) and Diabetes UK (grant number:18/0005870) and has been performed at the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (BRC) (NIHR203331). Funding for open access charge is from Wellcome Trust (grant number: 221690/Z/20/Z). Dr Chowdhary has received grants from the British Heart Foundation (grant number: FS/CRTF/20/24003). Dr Valkovič has received grants from the Sir Henry Dale Fellowship supported jointly by the Wellcome Trust and the Royal Society (#221805/Z/20/Z), and Slovak Grant Agencies VEGA (#2/0004/23) and APVV (#21-0299). Dr Levelt acknowledges support from the Wellcome Trust Clinical Career Development Fellowship (grant number: 221690/Z/20/Z), Diabetes UK (grant number: UK 18/0005908) and the NIHR Leeds Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial bridging (MB) is accompanied by the dynamic extravascular compression of epicardial coronary arteries, leading to intracoronary hemodynamic disturbance with abnormal coronary flow profiles. We aimed to evaluate the prognostic implications of resistive reserve ratio (RRR), a composite measure of flow and pressure parameters that represents the vasodilatory capacity of the coronary arteries, in patients with angina with nonobstructive coronary artery disease (ANOCA) and MB, in comparison with coronary flow reserve (CFR)., Methods and Results: In this retrospective cohort study, we included patients with ANOCA who underwent coronary reactivity testing, where MB was identified by transient constriction in coronary artery segments between systole and diastole. Abnormal CFR and RRR were defined as <2.5 and <2.62, respectively. Major adverse cardiac events, including cardiovascular death, stroke, myocardial infarction, heart failure, and late revascularization, served as outcomes. Among 1251 patients with ANOCA, 191 (15.3%) had MB. The prevalence of abnormal CFR or RRR was not significantly different between patients with and without MB ( P =0.144 and P =0.398, respectively). Over a median follow-up time of 6.9 years, abnormal RRR predicted major adverse cardiac events in patients with MB (hazard ratio [HR], 4.38 [95% CI, 1.71-11.21]; P =0.002) and without MB (HR, 1.91 [95% CI, 1.38-2.64]; P <0.001). Abnormal CFR predicted major adverse cardiac events in patients without MB (HR, 2.15 [95% CI, 1.54-3.00]; P <0.001), whereas it was not predictive of major adverse cardiac events in patients with MB (HR, 2.29 [95% CI, 0.93-5.65]; P =0.073)., Conclusions: In patients with ANOCA and MB, impaired RRR was superior to impaired CFR in distinguishing patients at a higher risk of future adverse events, suggesting that RRR may serve as a risk stratification tool in patients with MB and ANOCA.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease., Competing Interests: Disclosure Dr N.R. Smilowitz serves on an advisory board for Abbott Vascular. The remainder of the authors report no financial relationships or conflicts of interest regarding the content herein., (Published by Elsevier Inc.)

Aims: Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF., Methods and Results: A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P < 0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P < 0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P = 0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P = 0.04]., Conclusions: CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Coronary artery disease (CAD) is one of the leading causes of death globally. Currently, diagnosis and intervention in CAD are typically performed via minimally invasive cardiac catheterization procedures. Using current diagnostic technology, such as angiography and fractional flow reserve (FFR), interventional cardiologists must decide which patients require intervention and which can be deferred; 10% of patients with stable CAD are incorrectly deferred using current diagnostic best practices. By developing a forward-viewing intravascular ultrasound (FV-IVUS) 2-D array capable of simultaneously evaluating morphology, hemodynamics, and plaque composition, physicians would be better able to stratify risk of major adverse cardiac events in patients with intermediate stenosis. For this application, a forward-viewing, 16-MHz 2-D array transducer was designed and fabricated. A 2-mm-diameter aperture consisting of 140 elements, with element dimensions of 98×98×70 μ m ( w×h×t ) and a nominal interelement spacing of 120 μ m, was designed for this application based on simulations. The acoustic stack for this array was developed with a designed center frequency of 16 MHz. A novel via-less interconnect was developed to enable electrical connections to fan-out from a 140-element 2-D array with 120- μ m interelement spacing. The fabricated array transducer had 96/140 functioning elements operating at a center frequency of 16 MHz with a -6-dB fractional bandwidth of 62% ± 7 %. Single-element SNR was 23 ± 3 dB, and the measured electrical crosstalk was - 33 ± 3 dB. In imaging experiments, the measured lateral resolution was 0.231 mm and the measured axial resolution was 0.244 mm at a depth of 5 mm. Finally, the transducer was used to perform 3-D B-mode imaging of a 3-mm-diameter spring and 3-D B-mode and power Doppler imaging of a tissue-mimicking phantom.

Competing Interests: Disclosures The authors have no conflicts to disclose.