Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

Haemodynamics of stent-mounted neural interfaces in tapered and deformed blood vessels.

The endovascular neural interface provides an appealing minimally invasive alternative to invasive brain electrodes for recording and stimulation. However, stents placed in blood vessels have long been known to affect blood flow (haemodynamics) and lead to neointimal growth within the blood vessel. Both the stent elements (struts and electrodes) and blood vessel wall geometries can affect the mechanical environment on the blood vessel wall, which could lead to unfavourable vascular remodelling after stent placement. With increasing applications of stents and stent-like neural interfaces in venous blood vessels in the brain, it is necessary to understand how stents affect blood flow and tissue growth in veins. We explored the haemodynamics of a stent-mounted neural interface in a blood vessel model. Results indicated that blood vessel deformation and tapering caused a substantial change to the lumen geometry and the haemodynamics. The neointimal proliferation was evaluated in sheep implanted with an endovascular neural interface. Analysis showed a negative correlation with the mean Wall Shear Stress pattern. The results presented here indicate that the optimal stent oversizing ratio must be considered to minimise the haemodynamic impact of stenting.

Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicating that the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Research Progress and Clinical Value of Subendocardial Viability Ratio.

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with ischemic heart disease being a major contributor, either through coronary atherosclerotic plaque-related major vascular disease or coronary microvascular dysfunction. Obstruction of coronary blood flow impairs myocardial perfusion, which may lead to acute myocardial infarction in severe cases. The subendocardial viability ratio, also known as the Buckberg index, is a valuable tool for evaluation of myocardial perfusion because it reflects the balance between myocardial oxygen supply and oxygen demand. The subendocardial viability ratio can effectively evaluate the function of the coronary microcirculation and is associated with arterial stiffness. This ratio also has potential value in predicting adverse cardiovascular events and mortality in various populations. Moreover, the subendocardial viability ratio has demonstrated clinical significance in a range of diseases, including hypertension, aortic stenosis, peripheral arterial disease, chronic kidney disease, diabetes, and rheumatoid arthritis. This review summarizes the applications of the subendocardial viability ratio, its particular progress in the relevant research, and its clinical significance in cardiovascular diseases.

Impact of coronary hyperemia on collateral flow correction of coronary microvascular resistance indices.

Recently, a novel method to estimate wedge pressure (Pw)-corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since, and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of Pw measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw measurements and the derivation of Pw-corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for Pw measurements was validated by estimating the coronary fractional flow reserve (FFRcor) from myocardial fractional flow reserve (FFRmyo) in a Doppler-derived study population (N = 53). From these patients, 24 had hyperemic Pw measurements available for the evaluation of hyperemic conditions on the derivation of Pw and its effect on the derivation of both "true" (with measured Pw) and "estimated" Pw-corrected HMR. Nonhyperemic Pw differed significantly from Pw measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFRcor and FFRmyo in nonhyperemic conditions (R2 = 0.91, P < 0.005), as well as in hyperemic conditions (R2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic (R2 = 0.86, P < 0.005) or hyperemic conditions (R2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic Pw-corrected HMR and apparent HMR (R2 = 0.67, P < 0.005), hyperemic Pw-corrected HMR showed a strong agreement with apparent HMR (R2 = 0.88, P < 0.005). We validated the calculation method for Pw-corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of Pw and the derivation of Pw-corrected HMR.NEW & NOTEWORTHY The following are what is known: 1) wedge-pressure correction is often considered for the derivation of indices of minimal microvascular resistance, and 2) the Yong method for calculating wedge pressure-corrected index of microvascular resistance (IMR) without balloon inflation has never been validated in a Doppler-derived population and has not been tested under different physiological conditions. This study 1) adds validation for the Yong method for calculated wedge-pressure correction in a Doppler-derived study population and 2) shows significant influence of the physiological conditions on the derivation of coronary wedge pressure.

Establishment of nonobstructive coronary microcirculatory disorders in rabbits using three established methods and a comparative study.

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.

Measuring Absolute Coronary Flow and Microvascular Resistance by Thermodilution: JACC Review Topic of the Week.

Diagnosing coronary microvascular dysfunction remains challenging, primarily due to the lack of direct measurements of absolute coronary blood flow (Q) and microvascular resistance (Rµ). However, there has been recent progress with the development and validation of continuous intracoronary thermodilution, which offers a simplified and validated approach for clinical use. This technique enables direct quantification of Q and Rµ, leading to precise and accurate evaluation of the coronary microcirculation. To ensure consistent and reliable results, it is crucial to follow a standardized protocol when performing continuous intracoronary thermodilution measurements. This document aims to summarize the principles of thermodilution-derived absolute coronary flow measurements and propose a standardized method for conducting these assessments. The proposed standardization serves as a guide to ensure the best practice of the method, enhancing the clinical assessment of the coronary microcirculation.

PET evaluation of myocardial perfusion function after percutaneous coronary intervention in patients with chronic total occlusion: a systematic review and meta-analysis.

Objective. The benefit of percutaneous coronary intervention (PCI) in chronic complete coronary artery occlusion (CTO) remains controversial. PCI is currently indicated only for symptom and myocardial ischemia abolition, but large chronically occluded vessels with extensive afferent myocardial territories may benefit most from this procedure. The noninvasive evaluation of myocardial perfusion is critical before and after revascularization, and positron emission tomography (PET) can determine absolute myocardial perfusion. Here, we aimed to explore and compare myocardial perfusion in CTO territories and their remote associated areas before and after PCI. Design. We searched for relevant articles published before November 28, 2022, in the Cochrane Library and PubMed. We calculated 95% confidence intervals (CIs) and standardized mean differences (SMDs) for parameters related to myocardial perfusion in CTO territories and remote areas in CTO patients before and after PCI. Results. We included five studies published between 2017 and 2022, with a total of 592 patients. Stress myocardial blood flow (MBF) was increased in CTO territories after PCI when compared to pre-PCI (mean difference [MD]: 1.70, 95% confidence interval [CI] 1.33-2.08, p < 0.001). Coronary flow reserve (CFR) in CTO regions was also higher after PCI (MD 1.37,95% [CI]1.13-1.61, p < 0.001). Stress MBF in remote regions was also increased after PCI (MD 0.27,95% [CI]0.99 ∼ 0.45, p = 0.004), as was CFR in remote regions (MD 0.32,95% [CI] 0.14-0.5, p = 0.001). Conclusions. According to our pooled analysis of current literature, there was an increase in stress MBF and CFR in both CTOs and remote regions after PCI, suggesting that patients with CTO have widespread recovery of blood perfusion after the procedure. These results provide evidence that patients with CTO arteries and high ischemic burdens would indeed benefit from CTO-PCI. Future research on the correlation of ischemia burden reduction with hard clinical endpoints would contribute to a clearer demarcation of the role of CTO PCI with prognostic potential.

Investigation into the two-way interaction of coronary flow and heart function in coronary artery disease predicted by a computational model of autoregulation of coronary flow.

This study presents a closed-loop computational model to investigate the interplay between heart function, coronary flow, and systemic circulation during exercise, with a specific focus on the impact of coronary artery stenosis. The model incorporates a lumped representation of the heart, main arteries, and coronary arteries, establishing a closed circulatory system. The simulation investigates the autoregulation of coronary flow in response to myocardial oxygen demands during physical exercise by incorporating sympathetic and parasympathetic functions. This study establishes a closed supply-demand loop and investigates the effect of coronary flow deficiency on heart function and systemic circulation in coronary artery diseases during exercise. In coronary artery diseases with low stenosis, heart function and systemic flow resemble those of a healthy person. However, as stenosis intensifies with physical exercise, an additional regulatory mechanism (reg2) is activated. This mechanism adjusts coronary flow by reducing myocardial contractility (E) and increasing heart rate (HR) while maintaining cardiac output (CO). The study results indicate that, at the highest exercise intensity for a healthy individual (HR = 150), the value of E increases from 6 to 8.65mmHg/ml. Meanwhile, for a patient with 85 % coronary artery stenosis in the same exercise intensity, the HR increases to 200, and the value of E decreases to 3.45mmHg/ml. The results also demonstrate that the initiation of the (reg2) mechanism at rest occurs at 83 % stenosis, while at the highest exercise intensity, this mechanism commences at 67 % stenosis.

Impact of sex on the assessment of the microvascular resistance reserve.

BACKGROUND: The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. AIM: The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. METHODS: From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. RESULTS: A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47-0.96, p = 0.027) and men (HR 0.84, 0.74-0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. CONCLUSION: The MRR seems to be equally applicable in both women and men with stable coronary artery disease.

Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is the leading cause of ischemia with no obstructive coronary arteries disease (INOCA) disease. Diagnosis of CMD relies on surrogate physiological indices without objective proof of ischemia. OBJECTIVES: Intracoronary electrocardiogram (icECG) derived hyperemic indices may accurately and objectively detect CMD and reversible ischemia in related territory. METHODS: INOCA patients with proven ischemia by myocardial perfusion scan (MPS) and completely normal coronary arteries underwent simultaneous intracoronary electrophysiological (icECG) and physiological (intracoronary Doppler) assessment in all 3 coronary arteries during rest and under adenosine induced hyperemia. RESULTS: Sixty vessels in 21 patients were included in the final analysis. All patients had at least one vessel with abnormal CFR. 41 vessels had CMD (CFR < 2.5), of which 26 had increased microvascular resistance (structural CMD, HMR > 1.9 mmHg.cm-1.s) and 15 vessels had CMD (CFR < 2.5) with normal microvascular resistance (functional CMD, HMR <= 1.9 mmHg.cm-1.s). Only one-third of the patients (n = 7) had impaired CFR < 2.5 in all 3 epicardial arteries. Absolute ST shift between hyperemia and rest (∆ST) has shown the best diagnostic performance for ischemia (cut-off 0.10 mV, sensitivity: 95%, specificity: 72%, accuracy: 80%, AUC: 0.860) outperforming physiological indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002). CONCLUSIONS: In INOCA patients, CMD involves coronary artery territories heterogeneously. icECG can accurately detect CMD causing perfusion abnormalities in patients with INOCA outperforming physiological CMD markers, by demonstrating actual ischemia instead of predicting the likelihood of inducible ischemia based on violated surrogate thresholds of blunted flow reserve or increased minimum microvascular resistance. CONDENSED ABSTRACT: In 21 INOCA patients with coronary microvascular dysfunction (CMD) and myocardial perfusion scan proved ischemia, hyperemic indices of intracoronary electrocardiogram (icECG) have accurately detected vessel-specific CMD and resulting perfusion abnormalities & ischemia, outperforming invasive hemodynamic indices. Absolute ST shift between hyperemia and rest (∆ST) has shown the best classification performance for ischemia in no Obstructive Coronary Arteries (AUC: 0.860) outperforming Doppler derived CMD indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002).icECG can be used to diagnose CMD causing perfusion defects by demonstrating actual reversible ischemia at vessel-level during the initial CAG session, obviating the need for further costly ischemia tests. CLINICALTRIALS: GOV: NCT05471739.

Cut-off value for interleukin-34 as an additional potential inflammatory biomarker for estimation of slow coronary flow risk.

BACKGROUND: Inflammatory markers may provide insights into the underlying mechanisms of slow coronary flow (SCF), including subclinical atherosclerosis and endothelial dysfunction. Interleukin-34 (IL-34), known for its role in immuno-inflammatory diseases, might hold significance in SCF. We aimed to explore the potential association between IL-34 and SCF in patients undergoing diagnostic elective coronary angiography. METHODS: This observational, cross-sectional study enrolled 256 participants: 124 with SCF and 132 with normal coronary flow (NCF). All participants had undergone outpatient coronary angiography for suspected coronary artery disease. SCF assessment employed the TIMI frame count (TFC) for quantifying coronary flow rate. RESULTS: SCF patients exhibited significantly elevated TFC in all three major coronary arteries compared to controls (p < 0.05). IL-34 displayed a noteworthy positive correlation with average TFC [for all participants: r = 0.514, p < 0.001; for SCF patients: r = 0.526, p < 0.001; for normal controls: r = -0.288, p > 0.05]. Similarly, high-sensitivity C-reactive protein (hsCRP) showed a significant and positive relationship with average TFC [for all participants: r = 0.504, p < 0.001; for SCF patients: r = 0.558, p < 0.001; for normal controls: r = -0.148, p > 0.05]. SCF patients presented coronary arteries of larger size compared to controls. CONCLUSION: Mean coronary diameter and IL-34 emerged as independent predictors of SCF. Additionally, hsCRP, mean coronary diameter, and IL-34 exhibited a positive correlation with mean TFC values. IL-34 appears to be a more effective indicator than hsCRP in SCF patients.

Coronary Flow Reserve and Myocardial Resistance Reserve Changes After Transcatheter Aortic Valve Implantation in Aortic Stenosis.

Aortic valve stenosis (AS) induces an alteration in hemodynamic conditions that are responsible for coronary microvasculature impairment. Relief of AS by transcatheter aortic valve implantation (TAVI) is expected to improve the coronary artery hemodynamic. We aimed to assess the midterm effects of TAVI in coronary flow reserve (CFR) and myocardial resistance reserve (MRR) by a continuous intracoronary thermodilution technique. At-rest and hyperemic coronary flow was measured by a continuous thermodilution technique in 23 patients with AS and compared with that in 17 matched controls, and repeated 6 ± 3 months after TAVI in 11 of the patients with AS. In patients with AS, absolute coronary flow at rest was significantly greater, and absolute resistance at rest was significantly less, than in controls (p <0.01 for both), causing less CFR and MRR (1.73 ± 0.4 vs 2.85 ± 1.1, p <0.01 and 1.95 ± 0.4 vs 3.22 ± 1.4, p <0.01, respectively). TAVI implantation yielded a significant 35% increase in CFR (p >0.01) and a 39% increase in MRR (p <0.01) driven by absolute coronary flow at rest reduction (p = 0.03). In patients with AS, CFR and MRR determined by continuous thermodilution are significantly impaired. At 6-month follow-up, TAVI improves these indexes and partially relieves the pathophysiologic alterations, leading to a partial restoration of CFR and MRR.

Coronary Slow-Flow Phenomenon in Takotsubo Syndrome: The Prevalence, Clinical Determinants, and Long-Term Prognostic Impact.

Patients with takotsubo syndrome (TTS) may present coronary slow flow (CSF) in angiography performed in the acute myocardial infarction (MI). However, the detailed clinical relevance and its long-term impact remain poorly understood. Among 7771 MI patients hospitalized between 2012 and 2019, TTS was identified in 82 (1.1%) subjects. The epicardial blood flow was assessed with thrombolysis in myocardial infarction (TIMI) scale and corrected TIMI frame count (TFC), whereas myocardial perfusion with TIMI myocardial perfusion grade (TMPG). CSF was defined as TIMI-2 or corrected TFC > 27 frames in at least one epicardial vessel. CSF was identified in 33 (40.2%) TTS patients. In the CSF-TTS versus normal-flow-TTS group, lower values of left ventricular ejection fraction on admission (33.5 (25-40) vs. 40 (35-45)%, p = 0.019), more frequent midventricular TTS (27.3 vs. 8.2%, p = 0.020) and the coexistence of both physical and emotional triggers (9.1 vs. 0%, p = 0.032) were noted. Within a median observation of 55 months, higher all-cause mortality was found in CSF-TTS compared with normal-flow TTS (30.3 vs. 10.2%, p = 0.024). CSF was identified as an independent predictor of long-term mortality (hazard ratio 10.09, 95% confidence interval 2.12-48.00, p = 0.004). CSF identified in two-fifths of TTS patients was associated with unfavorable long-term outcomes.

Relation of Thrombolysis in Myocardial Infarction Frame Count to Invasively Measured Coronary Physiologic Indexes.

In the international guidelines, higher thrombolysis in myocardial infarction frame count (TFC) is indicated as evidence of coronary microvascular dysfunction (CMD). However, the association of TFC with invasively measured coronary physiologic parameters such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) remains unclear. Patients without significant epicardial coronary lesions underwent invasive coronary physiologic assessment using a thermodilution method in the left anterior descending artery. Corrected TFC (cTFC) was evaluated on coronary angiography. The cut-off values of CFR and IMR were defined as ≤2.0 and >25, and patients with abnormal CFR and/or IMR were defined as having CMD. This study aimed to assess whether cTFC >25, a cut-off value in the guidelines, was diagnostic of the presence of CMD. Of the 137 patients, 34 (24.8%) and 32 (23.3%) had cTFC >25 and CMD, respectively. The rate of CMD was not significantly different between patients with and without cTFC >25. cTFC was weakly correlated with at rest and hyperemic mean transit time and IMR, whereas no significant correlation was observed between cTFC and CFR. The receiver operating characteristic curve analysis showed the poor diagnostic ability of cTFC for abnormal CFR and IMR and the presence of CMD. In conclusion, in patients without epicardial coronary lesions, cTFC as a continuous value and with the cut-off value of 25 was not diagnostic of abnormal CFR and IMR and the presence of CMD. Our results did not support the use of cTFC in CMD evaluation.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

The diagnosis and treatment of women with recurrent cardiac ischemia and normal coronary arteries.

Cardiac disease is the leading cause of death in women. Among women with recurrent chest pain, abnormal electrocardiograms, and/or stress tests who undergo coronary angiography, as many as 50% have normal or <50% coronary artery obstructive disease. Pharmacologic stress assessment of coronary artery flow reserve in these women frequently demonstrates an inability to increase blood flow to >2.5 times normal flow. Contributory factors include abnormal epicardial or microvascular reactivity, microvascular remodeling or rarefaction, autonomic dysfunction, or coronary plaque rupture/erosion. Assessment is necessary of serum biomarkers and coronary artery flow reserve, fractional flow reserve, microvascular resistance, and epicardial/microvascular spasm. Aggressive treatment of women with positive tests is necessary because these women have an increased incidence of recurrent chest pain, repeated hospitalizations and coronary angiograms, and cardiac death.

Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters.

PURPOSE: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). METHODS: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood T 1 $$ {\mathrm{T}}_1 $$ relaxation time ( T 1 , B $$ {\mathrm{T}}_{1,B} $$ ) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific T 1 , B $$ {\mathrm{T}}_{1,B} $$ values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. RESULTS: Simulated and phantom experiments showed a strong dependence on AMS and FA ( R 2 $$ {R}^2 $$ >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ( R 2 $$ {R}^2 $$ >0.59) was observed which was reduced when calculating MBF with individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ . For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. CONCLUSION: Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ and a saturation-baseline can reduce these variations in spGRE and improve reproducibility of FAIR-myoASL against acquisition parameters.