Coronary Microcirculatory Function Research Articles

Prognostic Implications of Microvascular Resistance Reserve in Symptomatic Patients With Intermediate Coronary Stenosis

BackgroundMicrovascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). ObjectivesThe aim of this study was to evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. MethodsThe present study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiological assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR) ≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR ≤3.0. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. ResultsAmong the study group, 172 patients (31.4%) had FFR ≤0.80, and 200 patients (36.6%) had CMD defined by MRR ≤3.0. MRR showed no significant correlation with FFR (R = −0.031; P = 0.469), but it was significantly correlated with the index of microcirculatory resistance (R = −0.353; P < 0.001), N-terminal pro–B-type natriuretic peptide (R = −0.296; P < 0.001), left ventricular filling pressure (E/e′ ratio) (R = −0.224; P < 0.001), and diastolic dysfunction grade (P < 0.001). During a median follow-up period of 3.3 years (Q1-Q3: 2.0-4.5 years), MRR was significantly associated with MACE risk (HR: 1.23 per 1-U decrease; 95% CI: 1.12-1.36; P < 0.001). CMD defined by MRR ≤3.0 was associated with an increased MACE risk for both FFR >0.80 (41.0% vs 26.0%; adjusted HR: 1.59; 95% CI: 1.07-2.35; P = 0.021) and FFR ≤0.80 (34.7% vs 14.8%; adjusted HR: 2.32; 95% CI: 1.12-4.82; P = 0.024). ConclusionsDecreased MRR was associated with the presence of cardiac diastolic dysfunction as well as increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk for a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis. (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function [DIAST-CMD]; NCT05058833)

Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. Nine-hundred-seventeen coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22-50] vs 29 [21-41], p<0.001) was significantly higher and QFR (0.92 [0.78-0.99] vs 0.97 [0.91-0.99], p<0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (AUCROC 0.632 [95% CI 0.589-0.674], p<0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669-0.784], p<0.0001, p-value for AUCROC comparison=0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p-value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

The short-chain fatty acid propionate prevents ox-LDL-induced coronary microvascular dysfunction by alleviating endoplasmic reticulum stress in HCMECs.

Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to reduced endothelium-derived relaxing factor nitric oxide (NO) generation, causing and accelerating CMD. Endoplasmic reticulum stress (ER stress) has been shown to reduce NO production in umbilical vein endothelial cells. Oxidized low-density lipoprotein (ox-LDL) damages endothelial cell function. However, the relationship between ox-LDL and coronary microcirculation has yet to be assessed. Short-chain fatty acid (SCFA), a fermentation product of the gut microbiome, could improve endothelial-dependent vasodilation in human adipose arterioles, but the effect of SCFA on coronary microcirculation is unclear. In this study, we found ox-LDL stimulated expression of ER chaperone GRP78. Further, we activated downstream PERK/eIF2a, IRE1/JNK, and ATF6 signaling pathways, decreasing eNOS phosphorylation and NO production in human cardiac microvascular endothelial. Furthermore, SCFA-propionate can inhibit ox-LDL-induced eNOS phosphorylation reduction and raise NO production; the mechanism is related to the inhibition of ER stress and downstream signaling pathways PERK/eIF2a, IRE1/JNK, and ATF6. In summary, we demonstrate that ox-LDL induced CMD by activating ER stress, propionate can effectively counteract the adverse effects of ox-LDL and protect coronary microcirculation function via inhibiting ER stress.

SGLT2 expression in the left ventricle of cardiac patients is correlated with low-grade inflammation involving the pro-oxidant AT1R/NADPH oxidases/SGLT2 crosstalk: potential role in heart failure

Abstract Introduction Clinical studies showed that sodium-glucose co-transporter2 inhibitors (SGLT2i) have beneficial effects in heart failure patients regardless of ejection fraction and diabetes. Such cardiac diseases are often characterized by low-grade inflammation and impaired endothelial coronary microcirculation function. Recently, angiotensin II and TNF-α were shown to induce SGLT2 expression in endothelial cells (ECs) to sustain oxidative stress leading to endothelial dysfunction. However, the role and function of SGLT2 in the human left ventricle (LV) remain unclear. Therefore, this study evaluated the expression of SGLT2 in the LV of patients with cardiac diseases and, if so, determined the cellular localization, the underlying mechanism and the functional role. Methods Human LV biopsies were collected from 20 patients subjected to valve surgery at the Nouvel Hôpital Civil, Strasbourg, France. Expression levels of targets were determined by RT-qPCR and Western blot analysis, the in situ tissue localization by immunofluorescence (IF) staining and oxidative stress by dihydroethidium staining. Results RT-qPCR analysis of LV revealed variable SGLT1 and SGLT2 mRNA levels with no significant correlation. However, SGLT2 mRNA expression showed a positive correlation with those of pro-inflammatory markers (IL-1ß, IL-6, TNF-α, MCP-1 and CD68), AT1R, and VCAM-1. Western blot analysis confirmed the heterogenous SGLT2 protein expression level in LV with a difference up to 3.5-fold among the specimens. SGLT2 protein levels showed a positive correlation with markers of oxidative stress (phospho-p65 NF-κB, AT1R, nitrotyrosine) and markers of ECs activation (VCAM-1, ICAM-1), and a negative correlation with levels of eNOS. Further, immunofluorescence analysis of LV cryosections showed SGLT2 staining in the endothelium of the coronary microcirculation, as indicated by its co-localization with the endothelial cell marker CD31, and throughout the heart tissue. SGLT2 signals were also observed in areas showing IF signals for TNF-α, phospho-p65 NF-κB, CD68 and VCAM-1 suggesting that SGLT2 expression is localized to sites of inflammation. LV specimens with high SGLT2 protein levels showed elevated levels of oxidative stress, which were inhibited by N-acetylcysteine, VAS-2870, perindoprilat, losartan, empagliflozin, and infliximab. Conclusions The findings indicate that endothelial and cardiac SGLT2 expression in the LV of cardiac patients is associated with low-grade inflammation and oxidative stress. They further indicate that the pro-inflammatory cytokines/AT1R/NAPDH oxidases/SGLT2 crosstalk contributes to sustain a pro-oxidant state. Thus, SGLT2 inhibitors might ameliorate HF by mitigating the low-grade inflammatory-related pro-oxidant state and, hence, preserve the crucial endothelial control of the cardiomyocyte function in the LV.

Effects of remote ischemic preconditioning on coronary blood flow and microcirculation

This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.

Light-induced circadian rhythm disorder leads to microvascular dysfunction via up-regulating NETs

Circadian rhythm is a physical, mental, and behavioral pattern over the course of 24-hour cycle, and its disturbance is associated with increased risk of cardiovascular diseases. Microvascular dysfunction serves as an important cause of cardiovascular disease, but the relationship between rhythm disturbances and microcirculation remains elusive. Herein, we constructed the mice model of circadian rhythm disturbance and investigated the alterations of microvascular conditions. It was revealed that coronary microcirculatory function and cardiac diastolic function were significantly reduced, along with endothelium-dependent diastolic function of microvessels remarkably impaired in the rhythm-disordered group of mice compared to the control group. Notably, rhythm disturbance led to a significant upregulation of neutrophil extracellular traps (NETs) levels in mice, which cause endothelial dysfunction by inhibiting microvascular endothelial cell activity and migration capacity as well as inducing apoptosis. Additionally, intraperitoneal injection of Cl-amidine suppressed the production of NETs, which further improved coronary microcirculatory function and endothelium-dependent diastolic function. In conclusion, this study demonstrated that circadian rhythm disorders could induce the development of coronary microvascular dysfunction (CMD) through the up-regulation of NETs, providing a potential therapeutic direction for the treatment of CMD.

Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept study.

Coronary microvascular obstruction also known as no-reflow phenomenon is a major issue during myocardial infarction that bears important prognostic implications. Alterations of the microvascular network remains however challenging to assess as there is no imaging modality in the clinics that can image directly the coronary microvascular vessels. Ultrasound Localization Microscopy (ULM) imaging was recently introduced to map microvascular flows at high spatial resolution (∼10μm). In this study, we developed an approach to image alterations of the microvascular coronary flow in exvivo perfused swine hearts. A porcine model of myocardial ischemia-reperfusion was used to obtain microvascular coronary alterations and no-reflow. Four female hearts with myocardial infarction in addition to 6 controls were explanted and placed immediately in a dedicated preservation and perfusion box manufactured for ultrasound imaging. Microbubbles (MB) were injected into the vasculature to perform Ultrasound Localization Microscopy (ULM) imaging and a linear ultrasound probe mounted on a motorized device was used to scan the heart on multiple slices. The coronary microvascular anatomy and flow velocity was reconstructed using dedicated ULM algorithms and analyzed quantitatively. We were able to image the coronary microcirculation of exvivo swine hearts at a resolution of tens of microns and measure flow velocities ranging from 10mm/s in arterioles up to more than 200mm/s in epicardial arteries. Under different aortic perfusion pressures, we measured in large arteries of a subset of control hearts an increase of flow velocity from 31±11mm/s at 87mmHg to 47±17mm/s at 132mmHg (N=3 hearts, P<0.05). This increase was compared with a control measurement with a flowmeter in the aorta. We also compared 6 control hearts to 4 hearts in which no-reflow was induced by the occlusion and reperfusion of a coronary artery. Using average MB velocity and average density of MB per unit of surface as two ULM quantitative markers of perfusion, we were able to detect areas of coronary no-reflow in good agreement with a control anatomical pathology analysis of the cardiac tissue. In the no-reflow zone, we measured an average perfusion of 204±305MB/mm2 compared to 3182±1302MB/mm2 in the surrounding re-perfused area. We demonstrated this approach can directly image and quantify coronary microvascular obstruction and no-reflow on large mammal perfused hearts. This is a first step for noninvasive, quantitative and affordable assessment of the coronary microcirculation function and particularly coronary microvascular anatomy in the infarcted heart. This approach has the potential to be extended to other clinical situations characterized by microvascular dysfunction. This study was supported by the French National Research Agency (ANR) under ANR-21-CE19-0002 grant agreement.

Value of Myocardial Contrast Echocardiography in Detecting Coronary Microcirculatory Dysfunction in Ischemia With Non-obstructive Coronary Artery Disease

The aim of this study was to evaluate the value of myocardial contrast echocardiography (MCE) in detecting coronary microcirculation function dysfunction in ischemia with non-obstructive coronary artery (INOCA) disease. Twenty-one patients with a clinical diagnosis of INOCA were admitted to the First Affiliated Hospital of Xinjiang Medical University because of chest pain. All participants underwent MCE and [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography myocardial metabolic imaging. With the results of FDG PET taken as the gold standard, all myocardial segments were divided into a normal control group and a coronary artery microcirculation dysfunction (CMCD) group. We used MCE to measure myocardial perfusion parameters, including the ascending slope (β), time to peak (TTP), A and A×β. The receiver operating characteristic (ROC) curves of β, TTP, A and A×β were calculated to evaluate the diagnostic value of MCE for CMCD. A total of 122 and 218 segments were investigated in the CMCD and control groups, respectively. On the basis of the statistical analysis of the MCE parameters of the two groups, the myocardial perfusion parameters β, A and A×β of all segments in the CMCD group decreased, and the TTP in the basal segment of the CMCD group was longer than that of the normal control group (all p values <0.05). On the basis of analysis of the ROC curve, β had the highest diagnostic efficiency in the middle segment. This study found that MCE is valuable in the diagnosis of non-obstructive coronary artery complicated by CMCD.

Prognostic Value of Angiography-Derived Index of Microcirculatory Resistance in Patients with Coronary Artery Disease Undergoing Rotational Atherectomy

Background: Rotational atherectomy (RA) is the major tool used to treat severely calcified lesions in patients with coronary artery disease (CAD). The relationship between coronary microvascular dysfunction and RA remains unknown. Therefore, we attempted to explore the predictive implications of the coronary angiography-derived index of microcirculatory resistance (angio-IMR) in CAD patients undergoing RA. Methods: This retrospective study included 118 patients with severe coronary calcification who underwent a successful RA from January 2018 to June 2021. The angio-IMR was calculated based on computed flow and pressure dynamic principles to assess coronary microcirculatory function. Follow-up was performed on all patients for major adverse cardiovascular events (MACEs), including all-cause death, non-fatal myocardial infarction, target vessel revascularization (TVR), and stroke. Results: The mean angio-IMR for all patients was 25.58 ± 7.93. Patients were stratified the groups based on a mean angio-IMR of 25, fifty-four (45.8%) patients had angio-IMR ≥25. The logistic regression analysis showed that angiography-derived fractional flow reserve was significantly associated with coronary microvascular dysfunction. After median follow-up of 21.7 (15.1–24.0) months, MACEs occurred in 30.6%, including 12.5% all-cause deaths, 6.4% non-fatal myocardial infarction, 14.5% TVR, and 0.9% stroke. Kaplan-Meier analysis demonstrated that patients with angio-IMR ≥25 had greater cumulative MACEs (41.6%) and TVR (20.7%) than patients with preserved angio-IMR. COX regression analysis indicated that angio-IMR ≥25 and reduced left ventricular ejection fraction were independent predictors of MACEs. In addition, angio-IMR ≥25 and lowered minimum luminal area independently predicted TVR occurrence. Conclusions: In CAD patients undergoing RA, angio-IMR ≥25 was an independent and significant predictor of MACEs and TVR. Clinical Trial Registration: NCT05435898.

Differences in coronary flow reserve and flow-mediated dilation between plaque psoriasis and psoriatic arthritis

Abstract Background/Introduction Psoriatic disease is associated with increased cardiovascular risk through mechanisms of inflammation and oxidative stress. Purpose We aimed to investigate endothelial glycocalyx, coronary microcirculatory function and flow-mediated dilation in patients with plaque psoriasis and psoriatic arthritis. Methods In 311 patients (mean age: 52±12 years) with psoriatic disease (185 with plaque psoriasis and 126 with psoriatic arthritis) and 150 controls with similar age, sex and atherosclerotic risk factors, we assessed: (1) Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates impaired glycocalyx integrity. (2) Coronary flow reserve (CFR) in the distal left anterior descending coronary artery, (3) Flow-mediated dilation (FMD) of the brachial artery, and (4) LV global longitudinal strain (GLS) using speckle-tracking echocardiography. Results Compared with controls, patients with psoriatic disease had higher PBR (2.14±0.29 versus 1.78±0.25μm, p&amp;lt;0.001) and lower CFR (2.86±0.93 versus 3.39±0.68, p&amp;lt;0.001), FMD (6.97±3.9 versus 9.1±2.1, p&amp;lt;0.001) and GLS (−17.4±3.8 versus −21.9±1.5%, p&amp;lt;0.001). There was not significant difference between the two study groups (plaque psoriasis and psoriatic arthritis) in PBR (2.14±0.28 versus 2.14±0.31μm, p=0.990) and GLS (−17.2±3.9 versus −17.6±3.8%, p=0.297). Patients with psoriatic arthritis had more impaired CFR (2.75±0.85 versus 2.96±0.99, p=0.045) and FMD (5.45±3.2 versus 7.76±4, p=0.003) compared to patients with plaque psoriasis. Conclusions Patients with psoriatic disease have impaired endothelial, vascular and myocardial function compared with controls. Coronary microcirculatory function and flow-mediated dilation are more affected in psoriatic arthritis compared with plaque psoriasis. Funding Acknowledgement Type of funding sources: None.

Myocardial strain indices and coronary flow reserve are only mildly affected in healthy hypertensive patients

Abstract Hypertension is a major risk factor for cardiovascular disease and is associated with functional and structural changes in the heart and the vessels. Left ventricular deformation imaging with 2D Strain Echocardiography (2DSTE) and stress echocardiography with a vasodilator,such as dipyridamole (DIPSE), are useful tools for the detection of early myocardial abnormalities in hypertensive patients The aim of the current study was to investigate whether early (relatively healthy) hypertensive patients with normal left ventricular (LV) ejection fraction may differ in 2D Strain indices at baseline and in response to a stress test such as dipyridamole, compared to healthy controls. In the current study, the associations of 2DSTE indices and their changes following DIPSE with other studied parameters were also assessed. Forty-seven male hypertensive patients (aged 57±9 years) with normal ejection fraction and without left ventricular hypertrophy and 20 healthy male subjects were studied with conventional and 2D Strain echocardiography at rest and post DIPSE. Coronary flow reserve (CFR) in the left anterior descending artery following DIPSE was also evaluated. Global longitudinal strain (GLS) and TWIST were higher while UNTWIST rate was lower in hypertensives versus controls (p&amp;lt;0.05 for all). TWIST remained higher in hypertensives (p=0.021) after adjustment for differences in age and body mass index (BMI) between the groups. CFR was higher in controls compared to hypertensives even after adjustment for confounders (4.14 vs. 2.53, p=0.001). DIPSE-induced changes did not differ between the groups after adjustment for age and BMI (p&amp;gt;0.05 for all). DIPSE-induced improvement in GLS was associated with higher CFR only in hypertensive patients (r −0.372, p=0.010). The current study showed that well controlled hypertensive patients have mild echocardiographic differences compared to controls. Some of these differences appear to depend on age and Body mass index. A “hyper-rotation” phenomenon (higher TWIST) early in hypertension may be a compensatory mechanism to preserve global systolic LV function. Coronary microcirculatory function was impaired in hypertensive patients, albeit within normal range, and was associated with DIPSE-induced changes in myocardial long-axis systolic function. Funding Acknowledgement Type of funding sources: None.

Coronary microvascular dysfunction is associated with reduced cardiac performance in low flow low gradient aortic stenosis

Abstract Background Little is known about coronary microvascular function of patients with low-flow low-gradient aortic stenosis (LFLGAS). We hypothesized that LFLGAS is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac efficiency. Purpose To perform a prospective invasive assessment of CMD in patients with LFLGAS undergoing TAVI and to compare it with patients with NFHGAS. Moreover, we aimed to assess the possible acute impact of TAVI on coronary microvascular function and the interactions between CMD and of cardiac performance at speckle tracking echocardiography (STE). Methods Invasive thermodilution-based assessment was systematically performed in 41 consecutive patients with isolated severe AS with angiographic unobstructed coronary arteries undergoing TAVI. The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were derived to assess coronary microcirculatory function before and after TAVI. Advanced echocardiographic imaging, including STE, was performed to assess cardiac function. Results IMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 [14.6–39.1] vs 12.8 [8.6–19.2] p=0.002). Similarly, RRR was significantly lower in LFLGAS compared with NFHGAS (1.4 [1.1–2.1] vs 2.6 [1.5–3.3] p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index (rho=−0.427, p=0.005), low cardiac output (rho=−0.517, p=0.001), reduced peak atrial longitudinal strain (PALS) (rho=−0.610, p≤0.001) and presence of atrial fibrillation (54.6% vs 21.1%, p=0.036). Conversely, IMR was only modestly associated with the mean pressure aortic valve gradient (rho=−0.304, p=0.054). Notably, the mean gradient was significantly associated with IMR in the NFHGAS group (rho=0.632, p=0.003) but not in the LFLGAS (rho=−0.222, p=0.333). Similarly, high IMR was associated with the AVA in the NFHGAS group (rho=−0.50, p=0.025) but not in patients with LFLGAS (rho=0.157, p=0.497). Paradoxical LFLGAS emerged as a phenotype associated with CMD, poor left ventricular longitudinal systolic function and left atrial dysfunction. TAVI determined no significant variation in microvascular function (IMR: 16.0 [10.4–26.1] vs 16.6 [10.2–25.6], p=0.403) and in PALS (15.9 [9.9–26.5] vs 20.1 [12.3–26.7], p=0.222). Conversely, left ventricular global longitudinal strain increased overall after TAVI (−13.2 [8.4–16.6] vs −15.1 [9.4–17.8], p=0.047). Conclusions LFLGAS is associated with impaired coronary microvascular function compared with NFHGAS. Combined invasive assessment of microvascular function and advanced non-invasive imaging contributed to define different AS phenotypes. CMD was associated with low-flow state, left atrial dysfunction and reduced cardiac efficiency in patients with AS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott Vascular

Coronary Microcirculatory Function Indicated by Coronary Angiography-Derived Index of Microvascular Resistance in Patients Undergoing Rotational Atherectomy

Background: There are scarce published data reporting the effect of rotational atherectomy (RA) on coronary microcirculation function. Objectives: We aimed to evaluate coronary microcirculation function indicated by the coronary angiography-derived index of microvascular resistance (caIMR) in patients undergoing RA. Methods: RA procedures between January 2013 and December 2021 were retrospectively analyzed. We investigated coronary microcirculation function indicated by caIMR as well as peri-procedural adverse events among the study population. All caIMR measurements were performed using a FlashAngio system. The primary outcome was a composite of post-RA thrombolysis in myocardial infarction (TIMI) flow grade &lt;3 in the target vessel, myocardial injury, procedure-related myocardial infarction, and cardiac death during hospitalization. Results: A total of 155 RA procedures were analyzed. The post-RA caIMRs were significantly higher than pre-RA caIMRs in the target vessels (16.0 ± 7.0 vs. 14.5 ± 7.5, p = 0.029). Patients with post-RA caIMR ≥25 accounted for nearly 12% of those with pre-RA caIMR &lt;25. Patients with post-RA thrombolysis in myocardial infarction (TIMI) flow grade &lt;3 had a significantly higher pre-RA caIMR (23.5 ± 10.2 vs. 13.7 ± 6.6, p = 0.005), and the proportion of patients with pre-RA caIMR ≥25 in the group with TIMI flow grade &lt;3 was greater (61.5% vs. 38.5%, p &lt; 0.001) than that in the group with TIMI flow grade of 3. Maximum RA time of each pass (odds ratio: 1.127, 95% confidence interval: 1.025–1.239, p = 0.014) and pre-RA caIMR ≥25 (odds ratio: 3.254, 95% confidence interval: 1.054–10.048, p = 0.040) were identified to be the independent predictors of the primary outcome for patients who underwent RA. Conclusions: There were significant changes in the coronary microcirculation function of the target vessels after receiving RA as indicated by increased post-RA caIMR compared to pre-RA caIMR. Patients with baseline coronary microcirculatory dysfunction were more likely to have post-RA TIMI flow grade &lt;3, whereas those with pre-RA caIMR ≥25 experienced worse outcomes.

Cardiac Magnetic Resonance Assessment of the Protective Effect of Remote Ischemic Postconditioning on Coronary Microcirculation after Reperfusion Therapy for Acute ST-Segment Elevation Myocardial Infarction.

This study intends to evaluate the characteristics of coronary microcirculatory function in patients with myocardial infarction undergoing reperfusion and its predictive value in assessing cardiac function, myocardial activity, recovery of ventricular wall motion after infarction, and distant myocardial remodeling by cardiac magnetic resonance technique (CMRI). Materials and Methods. The 293 cases of patients with myocardial infarction treated in our hospital from August 2017 to August 2021 were selected as the subjects of this retrospective study, 13 cases were shed due to transfer and moving, and the rest were divided into 140 cases each in the emergency and elective groups according to emergency percutaneous coronary intervention (PCI) and elective PCI. The patients' myocardial infarct volume ventricular volume, microcirculatory obstruction volume ventricular volume, microcirculatory obstruction volume/myocardial infarct volume, and LVEF, combined with BP and troponin T, were analysed by CMR for comparative analysis, hemodynamic, and cardiac function index differences. Results. The hemodynamics (CO, CI, SV, SI, LVSW1, and LCW) measured at different times were significantly different between the two groups; patients in the emergency group had significantly lower EDV and ESV than the elective group at 7-10 d postoperatively; and EDV, ESV, and LVEF improved in both groups after 3 months, while EDV, ESV, and LVEF improved significantly better in the emergency group than in the elective group, and the difference was statistically significant (P < 0.05). The myocardial infarct quality, VSM score, and ventricular wall motion abnormality score were significantly lower in the emergency group than in the elective group from 7 to 10 d after PCI; myocardial infarct quality, VSM score, and ventricular wall motion abnormality score improved in both groups at 3 months after PCI; and the degree of improvement of myocardial infarct quality and VSM score was significantly better in the emergency group than in the elective group (P < 0.05). Conclusion. Acute myocardial infarction patients with significant effect of emergency PCI treatment can be on their postmyocardial infarction left ventricular function, and in the treatment of coronary heart disease, myocardial infarction diagnosis has a certain reference value.

Index of microcirculatory resistance: state-of-the-art and potential applications in computational simulation of coronary artery disease.

The dysfunction of coronary microcirculation is an important cause of coronary artery disease (CAD). The index of microcirculatory resistance (IMR) is a quantitative evaluation of coronary microcirculatory function, which provides a significant reference for the prediction, diagnosis, treatment, and prognosis of CAD. IMR also plays a key role in investigating the interaction between epicardial and microcirculatory dysfunctions, and is closely associated with coronary hemodynamic parameters such as flow rate, distal coronary pressure, and aortic pressure, which have been widely applied in computational studies of CAD. However, there is currently a lack of consensus across studies on the normal and pathological ranges of IMR. The relationships between IMR and coronary hemodynamic parameters have not been accurately quantified, which limits the application of IMR in computational CAD studies. In this paper, we discuss the research gaps between IMR and its potential applications in the computational simulation of CAD. Computational simulation based on the combination of IMR and other hemodynamic parameters is a promising technology to improve the diagnosis and guide clinical trials of CAD.

The Role of Coronary Physiology in Contemporary Percutaneous Coronary Interventions.

Invasive assessment of coronary physiology has radically changed the paradigm of myocardial revascularization in patients with coronary artery disease. Despite the prognostic improvement associated with ischemia-driven revascularization strategy, functional assessment of angiographic intermediate epicardial stenosis remains largely underused in clinical practice. Multiple tools have been developed or are under development in order to reduce the invasiveness, cost, and extra procedural time associated with the invasive assessment of coronary physiology. Besides epicardial stenosis, a growing body of evidence highlights the role of coronary microcirculation in regulating coronary flow with consequent pathophysiological and clinical and prognostic implications. Adequate assessment of coronary microcirculation function and integrity has then become another component of the decision-making algorithm for optimal diagnosis and treatment of coronary syndromes. This review aims at providing a comprehensive description of tools and techniques currently available in the catheterization laboratory to obtain a thorough and complete functional assessment of the entire coronary tree (both for the epicardial and microvascular compartments).

The effectiveness of alprostadil in treating coronary microcirculation dysfunction following ST-segment elevation myocardial infarction in a pig model.

Though alprostadil has been reported to improve the impaired microcirculation of patients with pulmonary arterial hypertension, its effectiveness as a treatment for coronary microvasculature dysfunction (CMD) following ST-segment elevation myocardial infarction (STEMI) is unknown. A total of 18 miniature pigs with CMD following STEMI were randomized into three groups that received an intracoronary injection of 5 ml of normal saline, 2 mg of nicorandil or 10 µg of alprostadil immediately after measurement of the index of microcirculatory resistance (IMR) and then an intravenous drip containing 5 ml of normal saline, 2 mg of nicorandil or 10 µg of alprostadil once a day for 6 days. The IMR, cardiac function using ultrasound, infarct areas and heparanase levels in infarct areas were measured and compared between the three groups. The IMR decreased markedly 10 min after alprostadil or nicorandil intracoronary injection (both P<0.05) but not following saline injection (P>0.05). After 7 days, the IMR was substantially lower in the alprostadil and nicorandil groups compared with the saline group (both P<0.05) and the ejection fraction was considerably higher in the alprostadil and nicorandil groups compared with the saline group (both P<0.05). Differences in infarct areas and the relative heparanase expression levels among the 3 groups were similar to the differences in the ejection fraction. No significant differences in the above assessment indexes were identified in the alprostadil and nicorandil groups. Alprostadil infusion improved coronary microcirculation function, reduced the infarct area and limited left ventricular dilatation in a pig coronary microvasculature dysfunction model following STEMI.

Endothelial glycocalyx integrity and microvascular perfusion are associated with novel echocardiographic markers and carotid intima-media thickness in patients with psoriasis

Abstract Background/Introduction Psoriasis has been associated with vascular and myocardial dysfunction through mechanisms of inflammation and oxidative stress. Purpose We aimed to evaluate sublingual microvascular perfusion and glycocalyx barrier properties in psoriasis patients, as well as their correlation with coronary microcirculatory function and markers of myocardial deformation and atherosclerosis (carotid intima-media thickness, cIMT). Methods We examined 297 patients with psoriasis and 150 controls, adjusted for age, sex, and atherosclerotic risk factors. Perfusion boundary region (PBR), a marker of glycocalyx barrier function, was measured non-invasively in sublingual microvessels with a diameter ranging from 5–25μm using a dedicated camera (Sidestream Dark Field imaging, Microscan, GlycoCheck). Increased PBR indicates reduced glycocalyx thickness. Indexes of microvascular perfusion, including red blood cell (RBC) filling percentage and functional microvascular density, were also calculated. We measured coronary flow reserve (CFR), cIMT and markers of myocardial deformation by speckle tracking imaging utilizing echocardiography [peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw-UtwMVO), at peak (%dpTw-UtwPEF), and the end of early LV diastolic filling (%dpTw-UtwEDF)]. Results Psoriasis patients had higher PBR5–25 compared to controls (2.13±0.29 versus 1.78±0.25μm, p&amp;lt;0.05). There was an inverse association of PBR5–25 with perfused microvascular density (r=−0.42, p&amp;lt;0.001) and RBC fraction (r=−0.80, p&amp;lt;0.001). In psoriatic population, PBR5–25 was inversely correlated to CFR (r=−0.30, p=0.045). Increased values of PBR5–9 were associated with reduced untwisting at the end of the mitral inflow E wave (r=−0.24, p=0.006) and reduced %dpTw-UtwMVO (r=−0.35, p&amp;lt;0.001). Furthermore, decreased RBC filling percentage and perfused microvascular density were related to worse LV longitudinal strain and increased cIMT (p&amp;lt;0.05). Finally, a positive correlation between perfused microvascular density and %dpTw-UtwMVO was observed in patients with psoriasis (p&amp;lt;0.05). Conclusion Endothelial glycocalyx thickness is reduced in patients with psoriasis and is associated with impaired coronary and myocardial function, and vascular atherosclerosis. Funding Acknowledgement Type of funding sources: None.

The association between invasive microvascular function and CMR-derived microvascular injury indicators and left ventricular function and infarct size at 1-month after reperfused STEMI

Abstract Background The restoration of the coronary microcirculation in ST-segment elevation myocardial infarction (STEMI) patients remains hampered in up to 50% of the STEMI patients after successful primary percutaneous coronary intervention (PCI). The association between the coronary microvascular function and injury indicators and functional outcome remains debated. Purpose This study aims to investigate the relation between post-PCI invasive microvascular function and cardiovascular magnetic resonance (CMR)-derived microvascular injury indicators and left ventricular (LV) function and infarct size (IS) at 1-month after STEMI. Methods The study was performed in 110 STEMI patients who underwent angiography for primary PCI and at 1-month follow-up. Invasive assessment of coronary microcirculation physiology in the culprit artery was performed during both procedures and included coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Data were available for 101 patients. A ratio of &amp;gt;2 for CFR and a value of &amp;lt;25 U for IMR were considered normal. CMR was performed during the acute phase (2 to 7 days after PCI) and at 1-month and provided assessment of LV function, IS and non-invasive information of microvascular injury in 78 patients by microvascular obstruction (MVO) and intra-myocardial hemorrhage (IMH). Results Over 1-month, CFR, IMR, LV function, and IS all significantly improved (p≤0.001). In univariable linear regression analysis, the post-PCI normal index CFR and IMR (both p=0.04), MVO presence, MVO size, IMH presence, IMH size (all, p&amp;lt;0.001) were significantly associated with LV ejection fraction at 1-month. Additionally, the post-PCI index CFR (p=0.04), MVO presence, MVO size, IMH presence, IMH size (all, p&amp;lt;0.001) were all associated with 1-month IS. In a multivariable linear regression analysis model including invasive and non-invasive coronary microcirculation function and injury indicators, MVO presence was identified as the only independent marker related to both 1-month LV ejection fraction and IS (both p&amp;lt;0.001). Conclusion(s) In STEMI patients, CMR-derived coronary microcirculation injury indicators reveal a closer association with 1-month LV function and IS outcome than invasive microcirculatory measurements. MVO presence is independently associated with 1-month LV ejection fraction and IS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The REDUCE-MVI study was funded by Astra Zeneca to MvL and NvR.

Posttraumatic Stress Disorder, Myocardial Perfusion, and Myocardial Blood Flow: A Longitudinal Twin Study

BackgroundThe link between posttraumatic stress disorder (PTSD) and ischemic heart disease remains elusive owing to a shortage of longitudinal studies with a clinical diagnosis of PTSD and objective measures of cardiac compromise. MethodsWe performed positron emission tomography in 275 twins who participated in two examinations approximately 12 years apart. At both visits, we obtained a clinical diagnosis of PTSD, which was classified as long-standing (both visit 1 and visit 2), late onset (only visit 2), and no PTSD (no PTSD at both visits). With positron emission tomography, we assessed myocardial flow reserve (MFR), which, in absence of significant coronary stenoses, indexes coronary microvascular function. We compared positron emission tomography data at visit 2 across the three categories of longitudinally assessed PTSD and examined changes between the two visits. ResultsOverall, 80% of the twins had no or minimal obstructive coronary disease. Yet, MFR was depressed in twins with PTSD and was progressively lower across groups with no PTSD (2.13), late-onset PTSD (1.97), and long-standing PTSD (1.93) (p = .01). A low MFR (a ratio <2.0) was present in 40% of the twins without PTSD, in 56% of those with late-onset PTSD, and in 72% of those with long-standing PTSD (p < .001). Associations persisted in multivariable analysis, when examining changes in MFR between visit 1 and visit 2, and within twin pairs. Results were similar by zygosity. ConclusionsLongitudinally, PTSD is associated with reduced coronary microcirculatory function and greater deterioration over time. The association is especially noted among twins with chronic, long-standing PTSD and is not confounded by shared environmental or genetic factors.