Coronary Microcirculatory Dysfunction Research Articles

Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

GSEA Analysis Identifies Potential Drug Targets and Their Interaction Networks in Coronary Microcirculation Disorders

Coronary microcirculation dysfunction (CMD) is one of the main causes of cardiovascular disease. Traditional treatment methods lack specificity, making it difficult to fully consider the differences in patient conditions and achieve effective treatment and intervention. The complexity and diversity of CMD require more standardized diagnosis and treatment plans to clarify the best treatment strategy and long-term outcomes. The existing treatment measures mainly focus on symptom management, including medication treatment, lifestyle intervention, and psychological therapy. However, the efficacy of these methods is not consistent for all patients, and the long-term efficacy is not yet clear. GSEA is a bioinformatics method used to interpret gene expression data, particularly for identifying the enrichment of predefined gene sets in gene expression data. In order to achieve personalized treatment and improve the quality and effectiveness of interventions, this article combined GSEA (Gene Set Enrichment Analysis) technology to conduct in-depth research on potential drug targets and their interaction networks in coronary microcirculation dysfunctions. This article first utilized the Coremine medical database, GeneCards, and DrugBank public databases to collect gene data. Then, filtering methods were used to preprocess the data, and GSEA was used to analyze the preprocessed gene expression data to identify and calculate pathways and enrichment scores related to CMD. Finally, protein sequence features were extracted through the calculation of autocorrelation features. To verify the effectiveness of GSEA, this article conducted experimental analysis from four aspects: precision, receiver operating characteristic (ROC) curve, correlation, and potential drug targets, and compared them with Gene Regulatory Networks (GRN) and Random Forest (RF) methods. The results showed that compared to the GRN and RF methods, the average precision of GSEA improved by 0.11. The conclusion indicated that GSEA helped identify and explore potential drug targets and their interaction networks, providing new ideas for personalized quality of CMD.

Impaired coronary flow reserve in patients with poor type 2 diabetes control: Preliminary results from prospective microvascular dysfunction registry.

Type 2 diabetes (DM) is a common comorbidity associated with cardiovascular disease, especially when poor glucose control is present. Extracardiac microcirculatory complications prevalence is well documented, however coronary microcirculatory dysfunction (CMD) seem to be underreported in this group. The present study analyzed coronary physiology measurements (coronary flow reserve [CFR], index of microcirculatory resistance [IMR], resistance reserve ratio [RRR]) in 47 diabetic patients (21 subjects with poor glycemia control defined as fasting glucose levels > 7.2 mmol/L and 26 with normal fasting glucose), and compared to 54 non-diabetic controls, who had undergone coronary angiography due to symptoms of chronic coronary syndrome. The median age of patients was 65.5 [59.0; 73.0] years old, 74% male, similar in terms of cardiovascular risk factors and prior myocardial infarction. Insulin was used by 19% of diabetic patients with poor glucose control and by 15% of those with DM and low fasting glucose. Prevalence of CMD was 38% in poor glycemia control patients, 27% in DM-patients with proper glucose control and 31% of non-diabetics. Median CFR values were the lowest in poor DM control patients compared to both, normal fasting glucose (1.75 [1.37; 2.32] vs. 2.30 [1.75; 2.85], p = 0.026) and to non-diabetics (1.75 [1.37; 2.32] vs. 2.15 [1.50; 2.95], p = 0.045). Levels of IMR, RRR and MRR did not differ significantly between compared groups (p > 0.05 for all comparisons). Poor glycemia control in type 2 DM might be associated with a higher prevalence of CMD driven by decreased coronary flow reserve, however, further research in larger groups of patients should be performed to confirm this observation.

Microcirculatory visualization and metabolomics of Dalbergia cochinchinensis in ameliorating coronary microvascular dysfunction in rats

This study employed microcirculation visualization and metabolomics methods to explore the effect and possible mechanism of Dalbergia cochinchinensis in ameliorating coronary microvascular dysfunction(CMD) induced by microsphere embolization in rats. Sixty SPF-grade male SD rats were randomized into sham, model, and low-, medium-, and high-dose [1.5, 3.0, and 6.0 g·kg~(-1)·d~(-1), respectively] D. cochinchinensis water extract groups. The rats in sham and model groups were administrated with equal volume of normal saline by gavage once a day for 7 consecutive days. The rat model of CMD was prepared by injecting polyethylene microspheres into the left ventricle, while the sham group was injected with an equal amount of normal saline. A blood flow meter was used to measure blood flow, and a blood rheometer to measure blood viscosity and fibrinogen content. An automatic biochemical analyzer and reagent kits were used to measure the serum levels of myocardial enzymes, glucose, and nitric oxide(NO). Hematoxylin-eosin(HE) staining was used to observe the pathological changes of myocardial tissue. DiI C12/C18 perfusion was used to infuse coronary microvessels, and the structural and morphological changes were observed using a confocal laser scanning microscope. AngioTool was used to analyze the vascular area, density, radius, and mean E lacunarity in the microsphere embolization area, and vascular blood flow resistance was calculated based on Poiseuille's law. Non-targeted metabolomics based on high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed screen potential biomarkers and differential metabolites regulated by D. cochinchinensis and the involved metabolic pathways were enriched. The pharmacodynamic results showed that compared with the model group, D. cochinchinensis significantly increased mean blood flow, reduced plasma fibrinogen content, lowered the levels of myocardial enzymes such as creatine kinase(CK), creatine kinase-MB(CK-MB), and lactate dehydrogenase(LDH), alleviate myocardial injury, and protect damaged myocardium. In addition, D. cochinchinensis significantly increased serum NO content, promoted vascular smooth muscle relaxation, dilated blood vessels, lowered serum glucose(GLU) level, improved myocardial energy metabolism, and alleviated pathological changes in myocardial fibrosis and inflammatory cell infiltration. The results of coronary microcirculation perfusion showed that D. cochinchinensis improved the vascular morphology, increased the vascular area, density, and radius, reduced vascular mean E lacunarity and blood flow resistance, and alleviated vascular endothelial damage in CMD rats. The results of metabolomics identified 45 differential metabolites between sham and model groups, and D. cochinchinensis recovered the levels 25 differential metabolites, which were involved in 8 pathways including arachidonic acid metabolism, arginine biosynthesis, and sphingolipids metabolism. D. cochinchinensis can ameliorate coronary microcirculation dysfunction caused by microsphere embolization in rats, and it may alleviate the pathological changes of CMD rats by regulating inflammatory reaction, endothelial damage, and phospholipid metabolism.

Diagnostic value of angiography-derived index of microcirculatory resistance (AMR) for coronary microcirculatory dysfunction (CMD) and its prognostic significance in patients with chronic coronary syndromes in the smoking population.

This study aims to analyze the prognostic significance of angiographic microvascular resistance (AMR) derived from functional coronary angiography in diagnosing coronary microvascular dysfunction (CMD) among patients with chronic coronary syndrome (CCS), particularly focusing on the prognostic significance of CMD in smokers. Additionally, this study assesses the prognostic significance of the diagnostic accuracy of the AMR index for CMD in CCS patients within the smoking population. Seventy-five CCS patients were studied for IMR measurement between June 2018 and December 2020, classified into CMD and non-CMD groups. Pearson correlation analyzed AMR and IMR relationship, while ROC curves determined AMR's predictive value for CMD with optimal cutoff value. An additional 223 CCS patients were included for AMR measurements. The study's primary endpoint was MACE occurrence, followed up through telephone calls. COX one-way analysis and Kaplan-Meier analysis evaluated the association between AMR and MACE risk. In the study, 52% of patients were diagnosed with CMD, and the AUC under the AMR curve for predicted IMR ≥ 25 was 0.90 (95% CI: 0.79-0.95). The CMD group had a higher proportion of female patients, smokers, and those with hypertension and diabetes mellitus compared to the non-CMD group (all P < .05). The CMD group exhibited higher AMR values than the non-CMD group (3.20 ± 0.5 vs 1.95 ± 0.45, P < .01), with a significant correlation between AMR and IMR (R2 = 0.81, P < .001). The ROC curve illustrated AMR's effectiveness in diagnosing CMD in CCS patients, using IMR as the gold standard, with the optimal cutoff value of AMR = 2.6mmHgs/cm (sensitivity: 90.5%, specificity: 81.5%). Patients with AMR ≥ 2.6mmHgs/cm had a higher risk of MACE events (HR = 6.00; 95% CI: 1.59-22.67). AMR in patients with CCS was significantly correlated with IMR and demonstrated good diagnostic accuracy. AMR ≥ 2.6 mm Hg*s/cm was associated with an increased risk of MACE occurrence and served as a valuable prognostic factor. In patients with CCS, AMR has a high diagnostic performance, In patients with CCS who smoke, impaired coronary microvascular function as assessed by AMR is significant and is an independent predictor of MACE.

Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy.

HIV infection and abacavir-containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)-derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well-validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non-HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non-abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR. Thirty-seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross-sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68-1.98] versus 2.40 mL/min per g [95% CI, 2.25-2.54]; P<0.001) and MBFR (2.18 [95% CI, 1.96-2.40] versus 2.68 [95% CI, 2.47-2.89]; P=0.002) was significantly lower in PWH than in people without HIV. In a single-arm, multicenter trial, a subset of 25 PWH who were virologically suppressed on dolutegravir/lamivudine/abacavir underwent positron emission tomography myocardial perfusion imaging at baseline and after switching to bictegravir/emtricitabine/TAF. MBFR was unchanged after switching to bictegravir/emtricitabine/TAF for a mean of 27 weeks (MBFR, 2.34 to 2.29; P=0.61), except in PWH with impaired MBFR at baseline (<2.00; N=6) in whom MBFR increased from 1.58 to 2.02 (P=0.02). PWH had reduced coronary microvascular function compared with controls without HIV. Coronary microvascular function did not improve after switching from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/TAF. URL: https://www.clinicaltrials.gov; unique identifier: NCT03656783.

Anatomical, functional and prognostic correlates of resting coronary flow velocity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical significance of baseline peak diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery (LAD) has not been investigated yet in patients with hypertrophic cardiomyopathy (HCM). Aim To assess the anatomical, functional and prognostic correlates of baseline LAD CFV in HCM. Methods 384 consecutive adult HCM patients (age=52+15 years, 164 [43%] females) with no known coronary artery disease from 8 centers in 5 countries were prospectively analyzed. All patients underwent comprehensive transthoracic echocardiography including CFV measurement with pulse wave Doppler in the mid-distal LAD. All patients had preserved left ventricular (LV) function. LV force was calculated as (peak instantaneous LV outflow tract gradient+systolic blood pressure)/LV end-systolic volume. Patients were followed for a median of 50 months (IQ range 18-97 months), the outcome measure was a composite endpoint of all-cause death and acute heart failure. Results The mean CFV was 36±11 cm/s. CFV was positively correlated with LV maximal wall thickness (r=0.375, p&amp;lt;0.001), LV maximal septal thickness (r=0.320, p&amp;lt;0.001), resting LV outflow tract gradient (r=0.274, p&amp;lt;0.001), LV force (r=0.227, p&amp;lt;0.001), mean E/e’ (r=0.479, p&amp;lt;0.001) and heart rate (r=0.221, p&amp;lt;0.001). During follow-up, 54 events occurred (33 all-cause deaths and 21 acute heart failures). Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (&amp;gt;31 cm/s) to predict the composite endpoint. Patients with CFV &amp;gt;31 cm/s had a significantly worse 10-year event-free survival compared to those with CFV ≤31 cm/s, see Figure. Conclusion Higher resting LAD CFV is associated with greater LV wall thickness, higher LV outflow tract gradient, faster heart rate and more elevated left ventricular filling pressures in HCM. Elevated resting CFV may indicate a coronary microcirculation dysfunction either primary or secondary to anatomical (septal hypertrophy), functional (increased myocardial oxygen demand), or autonomic (increased sympathetic drive) determinants. Whatever the underlying endotype, high resting CFV is related to worse prognosis in the long term.Figure.

Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.

Coronary microvascular endothelial cells (CMECs) react to changes in coronary blood flow and myocardial metabolites and regulate coronary blood flow by balancing vasoconstrictors-such as endothelin-1-and the vessel dilators prostaglandin, nitric oxide, and endothelium-dependent hyperpolarizing factor. Coronary microvascular endothelial cell dysfunction is caused by several cardiovascular risk factors and chronic rheumatic diseases that impact CMEC blood flow regulation, resulting in coronary microcirculation dysfunction (CMD). The mechanisms of CMEC dysfunction are not fully understood. However, the following could be important mechanisms: the overexpression and activation of nicotinamide adenine dinucleotide phosphate oxidase (Nox), and mineralocorticoid receptors; the involvement of reactive oxygen species (ROS) caused by a decreased expression of sirtuins (SIRT3/SIRT1); forkhead box O3; and a decreased SKCA/IKCA expression in the endothelium-dependent hyperpolarizing factor electrical signal pathway. In addition, p66Shc is an adapter protein that promotes oxidative stress; although there are no studies on its involvement with cardiac microvessels, it is possible it plays an important role in CMD.

Coronary microcirculatory dysfunction can be assessed by positive dicrotic wave and amplitude index on resting distal coronary pressure waveform, a newly developed index.

Some lesions have high resting distal coronary pressure/aortic pressure (Pd/Pa) despite low fractional flow reserve (FFR). This study aimed to assess microcirculatory dysfunction as a possible basal mechanism. Patients were grouped into two according to coffee intake (caffeine 222 mg) before coronary angiography. Through an adenosine-induced Pd/Pa decrease, amplitude index was calculated by dividing the difference between the highest pressure after the inflection point and the minimal diastolic pressure by the pulse pressure on the Pd waveform. In 130 coronary lesions (caffeine group, n = 69; non-caffeine group, n = 61) from 113 patients, the amplitude index through the adenosine-induced Pd/Pa decrease in all lesions was 0.54 ± 0.11 at resting Pd/Pa and 0.44 ± 0.12 at FFR (P < 0.0001). The positive dicrotic wave distribution on a maximal hyperaemia (FFRnicr)-resting Pd/Pa graph was analysed. In lesions with FFRnicr <0.80 on the FFRnicr-resting Pd/Pa graph, the resting Pd/Pa was divided into three zones based on Pd/Pa values: high-remaining, intermediate, and low. The high-remaining zone had a higher amplitude index than the intermediate zone (0.60 ± 0.09 vs. 0.48 ± 0.12; P < 0.005); the low zone lesions had no inflection point (no amplitude index). The high-remaining zone correlated with a larger positive dicrotic wave than the intermediate zone (94 vs. 30%; P < 0.005). Most lesions in the high-remaining zone corresponded to the caffeine group. In severe coronary stenosis, a high-remaining resting Pd/Pa with a high amplitude index or a positive dicrotic wave on the resting Pd waveform suggests microcirculatory dysfunction, such as insufficient arteriolar dilation reactive to myocardial ischaemia. UMIN000046883.

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.

Microcirculatory Disease in Patients after Heart Transplantation.

Although the treatment and prognosis of patients after heart transplantation have significantly improved, late graft dysfunction remains a critical problem. Two main subtypes of late graft dysfunction are currently described: acute allograft rejection and cardiac allograft vasculopathy, and microvascular dysfunction appears to be the first stage of both. Studies revealed that coronary microcirculation dysfunction, assessed by invasive methods in the early post-transplant period, correlates with a higher risk of late graft dysfunction and death during long-term follow-up. The index of microcirculatory resistance, measured early after heart transplantation, might identify the patients at higher risk of acute cellular rejection and major adverse cardiovascular events. It may also allow optimization and enhancement of post-transplantation management. Moreover, cardiac allograft vasculopathy is an independent prognostic factor for transplant rejection and survival rate. The studies showed that the index of microcirculatory resistance correlates with anatomic changes and reflects the deteriorating physiology of the epicardial arteries. In conclusion, invasive assessment of the coronary microcirculation, including the measurement of the microcirculatory resistance index, is a promising approach to predict graft dysfunction, especially the acute allograft rejection subtype, during the first year after heart transplantation. However, further advanced studies are needed to fully grasp the importance of microcirculatory dysfunction in patients after heart transplantation.

Ticagrelor vs. clopidogrel for coronary microvascular dysfunction in patients with STEMI: a meta-analysis of randomized controlled trials.

Approximately half of ST-segment elevation myocardial infarction (STEMI) patients who undergo revascularization present with coronary microvascular dysfunction. Dual antiplatelet therapy, consisting of aspirin and a P2Y12 inhibitor (e.g., clopidogrel or ticagrelor), is recommended to reduce rates of cardiovascular events after STEMI. The present study performed a pooled analysis of randomized controlled trials (RCTs) to compare effects of ticagrelor and clopidogrel on coronary microcirculation dysfunction in STEMI patients who underwent the primary percutaneous coronary intervention. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible RCTs up to September 2022, with no language restriction. Coronary microcirculation indicators included the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), myocardial blush grade (MBG), TIMI myocardial perfusion grade (TMPG), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). Seven RCTs that included a total of 957 patients (476 who were treated with ticagrelor and 481 who were treated with clopidogrel) were included. Compared with clopidogrel, ticagrelor better accelerated microcirculation blood flow [cTFC = -2.40, 95% confidence interval (CI): -3.38 to -1.41, p < 0.001] and improved myocardial perfusion [MBG = 3, odds ratio (OR) = 1.99, 95% CI: 1.35 to 2.93, p < 0.001; MBG ≥ 2, OR = 2.57, 95% CI: 1.61 to 4.12, p < 0.001]. Ticagrelor has more benefits for coronary microcirculation than clopidogrel in STEMI patients who undergo the primary percutaneous coronary intervention. However, recommendations for which P2Y12 receptor inhibitor should be used in STEMI patients should be provided according to results of studies that investigate clinical outcomes.

The Impact of Trimethylamine N-Oxide and Coronary Microcirculatory Dysfunction on Outcomes following ST-Elevation Myocardial Infarction

Persistent coronary microcirculatory dysfunction (CMD) and elevated trimethylamine N-oxide (TMAO) levels after ST-elevation myocardial infarction (STEMI) may drive negative structural and electrical cardiac remodeling, resulting in new-onset atrial fibrillation (AF) and a decrease in left ventricular ejection fraction (LVEF). TMAO and CMD are investigated as potential predictors of new-onset AF and left ventricular remodeling following STEMI. This prospective study included STEMI patients who had primary percutaneous coronary intervention (PCI) followed by staged PCI three months later. Cardiac ultrasound images were obtained at baseline and after 12 months to assess LVEF. Coronary flow reserve (CFR), and index of microvascular resistance (IMR) were assessed using the coronary pressure wire during the staged PCI. Microcirculatory dysfunction was defined as having an IMR value ≥25 U and CFR value <2.5 U. A total of 200 patients were included in the study. Patients were categorized according to whether or not they had CMD. Neither group differed from the other with regards to known risk factors. Despite making up only 40.5% of the study population, females represented 67.4% of the CMD group p < 0.001. Similarly, CMD patients had a much higher prevalence of diabetes than those without CMD (45.7% vs. 18.2%; p < 0.001). At the one-year follow-up, the LVEF in the CMD group had decreased to significantly lower levels than those in the non-CMD group (40% vs. 50%; p < 0.001), whereas it had been higher in the CMD group at baseline (45% vs. 40%; p = 0.019). Similarly, during the follow-up, the CMD group had a greater incidence of AF (32.6% vs. 4.5%; p < 0.001). In the adjusted multivariable analysis, the IMR and TMAO were associated with increased odds of AF development (OR: 1.066, 95% CI: 1.018-1.117, p = 0.007), and (OR: 1.290, 95% CI: 1.002-1.660, p = 0.048), respectively. Similarly, elevated levels of IMR and TMAO were linked with decreased odds of LVEF improvement, while higher CFR values are related to a greater likelihood of LVEF improvement. CMD and elevated TMAO levels were highly prevalent three months after STEMI. Patients with CMD had an increased incidence of AF and a lower LVEF 12 months after STEMI.

Molecular Mechanisms and Therapeutic Implications of Endothelial Dysfunction in Patients with Heart Failure

Heart failure is a complex medical syndrome that is attributed to a number of risk factors; nevertheless, its clinical presentation is quite similar among the different etiologies. Heart failure displays a rapidly increasing prevalence due to the aging of the population and the success of medical treatment and devices. The pathophysiology of heart failure comprises several mechanisms, such as activation of neurohormonal systems, oxidative stress, dysfunctional calcium handling, impaired energy utilization, mitochondrial dysfunction, and inflammation, which are also implicated in the development of endothelial dysfunction. Heart failure with reduced ejection fraction is usually the result of myocardial loss, which progressively ends in myocardial remodeling. On the other hand, heart failure with preserved ejection fraction is common in patients with comorbidities such as diabetes mellitus, obesity, and hypertension, which trigger the creation of a micro-environment of chronic, ongoing inflammation. Interestingly, endothelial dysfunction of both peripheral vessels and coronary epicardial vessels and microcirculation is a common characteristic of both categories of heart failure and has been associated with worse cardiovascular outcomes. Indeed, exercise training and several heart failure drug categories display favorable effects against endothelial dysfunction apart from their established direct myocardial benefit.

Takotsubo Syndrome: The Secret Crosstalk between Heart and Brain

An acute, transient episode of left ventricular dysfunction characterizes Takotsubo syndrome. It represents about 2% of all cases of acute coronary syndrome (ACS), and occurs predominantly in postmenopausal women, generally following a significant physical or emotional stressor. It can be diagnosed based on clinical symptoms and the absence of coronary artery disease on angiography. Ventriculography remains the gold standard for the diagnosis. Despite its transitory characteristic Takotsubo syndrome should not be considered a benign condition since complications occur in almost half of the patients, and the mortality rate reaches 4–5%. Lately, it has been revealed that Takotsubo syndrome can also lead to permanent myocardial damage due to the massive release of catecholamines that leads to myocardial dysfunction. Different mechanisms have been advanced to explain this fascinating syndrome, such as plaque rupture and thrombosis, coronary spasm, microcirculatory dysfunction, catecholamine toxicity, and activation of myocardial survival pathways. Here are still several issues with Takotsubo syndrome that need to be investigated: the complex relationship between the heart and the brain, the risk of permanent myocardial damage, and the impairment of cardiomyocyte. Our review aims to elucidate the pathophysiology and the mechanisms underlying this complex disease to manage the diagnostic and therapeutic algorithms to create a functional synergy between physicians and patients.

The change of angina levels in patients with chronic coronary syndromes and coronary microcirculatory dysfunction - a prospective study with 24 months follow-up.

A substantial proportion of patients with chronic coronary syndromes suffer from angina even after medical treatment and revascularization. Coronary microvascular dysfunction (CMD) is discussed as a potential mechanism. To assess angina status in patients with chronic coronary syndromes undergoing functional assessment of coronary circulation regarding the presence of coronary microcirculatory dysfunction. The study included 101 consecutive patients referred for coronary angiography requiring functional stenosis assessment, with median age of 66 years, 74% male, diagnosed or treated for dyslipidemia (91%) and diabetes type 2 (42%), 20% with a history of prior non-ST myocardial infarction. Fractional flow reserve (FFR), coronary flow reserve (CFR), resistive reserve ratio (RRR), and index of microcirculatory resistance (IMR) were measured. The diagnosis of CMD was defined by either IMR ≥ 25 units or CFR ≤ 2.0 in case of no significant stenosis. A change of one CCS class over 24 months follow-up was considered clinically significant. In patients without CMD diagnosis, there was a significant decrease in angina intensity (p < 0.001). Lack of angina improvement was associated with lower median RRR (2.30 (1.70, 3.30) vs. 3.05 (2.08, 4.10), p = 0.004) and lower median CFR (1.90 (1.40, 2.50) vs. 2.30 (IQR: 1.60, 3.00), p = 0.021), as compared to patients with angina improvement. The presence of CMD is a risk factor for no angina improvement. Impaired coronary resistive reserve ratio and lower microvascular reactivity may be one of the pathomechanisms leading to the lack of angina improvement in patients with chronic coronary syndromes.

Coronary microcirculation dysfunction evaluated by myocardial contrast echocardiography predicts poor prognosis in patients with ST-segment elevation myocardial infarction after percutaneous coronary intervention

BackgroundThe mortality rate of acute ST-segment elevation myocardial infarction (STEMI) remains substantial, despite advances in treatment strategies. Coronary microcirculation dysfunction (CMD) persists after percutaneous coronary intervention (PCI) in a substantial proportion of STEMI patients. The association between CMD assessed using myocardial contrast echocardiography (MCE) and prognosis requires further elucidation. This study aimed to evaluate the impact of CMD after successful PCI on the prognosis of patients with STEMI.MethodsWe enrolled 167 patients with STEMI after PCI who underwent MCE during hospitalization between January 2018 and March 2022. Patients were classified into the CMD and non-CMD groups according to the results of MCE. The clinical data and MCE results of both groups were analyzed. Follow-up was conducted for major adverse cardiac events.ResultsMCE detected CMD in 105 patients (62.9%). The CMD group contained fewer hypertensive patients (55.2% versus 74.2%, P = 0.015). Patients with CMD exhibited significantly higher levels of plasma troponin I (TnI) [73.2 (23.0–124.0) versus 28.9 (12.7–80.2) ng/mL, P = 0.004], higher levels of plasma B-type natriuretic peptide [255 (99–641) versus 193 (59–389) pg/mL, P = 0.004], poorer Killip classification (P = 0.038), and different culprit vessels (P < 0.001) compared to the non-CMD group. Patients with CMD exhibited lower left ventricular ejection fraction [50 (43–58) versus 61 (54–67) %, P < 0.001], poorer wall motion score index values (1.68 ± 0.4 versus 1.31 ± 0.26, P < 0.001) and poorer left ventricular global longitudinal strain [–11.2 (–8.7 to –14.1) versus –13.9 (–11.0 to –17.2) %, P < 0.001] compared to the non-CMD group. Patients underwent follow-up for 13 (7–20) months. After adjusting for hypertension, peak TnI level, culprit vessel, and Killip classification, CMD was an independent predictor of total major adverse cardiac events at 13 months’ follow-up [adjusted odds ratio (OR), 2.457; 95% confidence interval (CI), 1.042–5.790; P = 0.040], and patients with CMD had a higher risk of hospitalization for heart failure (adjusted OR, 5.184; 95% CI, 1.044–25.747; P = 0.044) and repeat myocardial infarction (adjusted OR, 2.896; 95% CI, 1.109–7.565; P = 0.030).ConclusionsMCE is a safe and effective method for detecting CMD in patients with STEMI. CMD detected by MCE after successful PCI in patients with STEMI is a common occurrence, which is associated with a significantly worse prognosis, especially hospitalization for heart failure and repeat myocardial infarction.

Acute Complications in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries: A Systematic Review with Special Focus on Mechanical Complications

Background: Recently, we have observed an increasing focus on myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) patients. MINOCA incidence is estimated to be within the range of 5–15% of all MI cases. Unfortunately, MINOCA relates to various conditions that are not rarely hard to identify, including coronary microcirculation dysfunction, epicardial coronary spasm, or plaque erosion. Our systematic review aimed to identify and appraise previous studies which characterized acute complications, with particular focus on mechanical complications, in patients with MINOCA. Methods: Applying the MeSH strategy in PubMed and Embase, two operators independently and systematically reviewed published studies on patients diagnosed with MINOCA and in whom acute complications were described. Papers published in the last 10 years (June 2012–June 2022) to reflect the introduction of the MINOCA definition as well as the current clinical practice were analyzed. The research was conducted in July 2022. Results: The search yielded 192 records. After abstract review, 79 papers were left, and after full-text analysis, we finally included 20 studies. Among 20 studies, there were: one randomized controlled trial, one prospective study, five retrospective studies, 1 case series, and 12 case reports with a total number of 337,385 patients. In the identified literature, we revealed 7 cases of intraventricular septal rupture, 3 cases of free wall rupture with pericardial effusion or cardiac tamponade, and 3 cases of bleeding complications (intracerebral or intestinal bleeding). Moreover, the ventricular arrhythmia incidence ranged from 2% to 13.8%, and the in-hospital death rate ranged from 0.9% to 6.4%. Conclusions: These findings suggest that MINOCA patients should be treated as standard MI patients with watchful monitoring, especially in the first few days.

Influence of fasting plasma glucose-lowering rate on BNP levels in type 2 diabetes mellitus patients with coronary microcirculation dysfunction.

The aim was to analyze the influence of fasting plasma glucose-lowering rate (FPGLR) on plasma BNP levels in type 2 diabetes mellitus (T2DM) patients with coronary microcirculation dysfunction (CMD) and to determine the optimal FPGLR for these patients. A total of 170 T2DM patients who received intensive glucose-lowering therapy during hospitalization in the First Affiliated Hospital of Harbin Medical University were enrolled. Ninety-two patients with CMD and 78 patients without CMD were assigned to a study and a control group, respectively. The study group was stratified as S1 (4.1 ~ 6.0mmol·L-1·day-1), S2 (2.1 ~ 4.0mmol·L-1·day-1), and S3 (≤ 2.0mmol·L-1·day-1) by different FPGLR, and the same in the control group (C1, C2, and C3). The plasma BNP levels with the same FPGLR were compared between the study and the control group, and patients with a different FPGLR in the study group were also compared. In the study and the control group, the BNP level in S1 was significantly higher than that in C1 (87 vs. 12pg/ml, P < 0.001), although there was no significant difference between S2 and C2, S3 and C3. In the study group, the BNP level in S1 was significantly higher than that in S2 (87 vs. 22pg/ml, P < 0.001) and S3 (87 vs. 15pg/ml, P < 0.001), but there was no significant difference between S2 and S3. Rapid intensive glucose-lowering may lead to increased plasma BNP levels in T2DM patients with CMD. Optimal FPGLR for these patients was determined to be no more than 4.0mmol·L-1·day-1.

Abstract 11065: Stress T1 Mapping Demonstrates Coronary Microcirculatory Dysfunction in Both Nonhypertrophied and Hypertrophied Myocardium of Hypertrophic Cardiomyopathy

Introduction: Coronary microcirculatory dysfunction (CMD) in hypertrophic cardiomyopathy (HCM) is associated with clinical deterioration. We have shown that stress T1 mapping could detect CMD of hypertrophied interventricular septum (IVS). However, CMD in nonhypertrophied left ventricular free wall (LVFW) has not been fully elucidated. Hypothesis: We assessed the hypothesis that regional CMD in LVFW of HCM can be detected using stress T1 mapping. Methods: We evaluated 36 consecutive subjects (26 HCM patients and 10 control subjects, mean age: 61±3 years) who underwent CMR at 3T. Cine imaging, rest and adenosine stress T1 mapping, late gadolinium enhancement (LGE) and phase-contrast imaging of coronary sinus flow were performed. The T1 values at rest and after adenosine stress were measured as an averaged T values of 3 short-axis slices of LV myocardium and T1 reactivity (ΔT1) was calculated as follows: ΔT1 (%) = (T1stress - T1rest)/T1rest х 100. Coronary flow reserve (CFR) was measured coronary sinus blood flow during adenosine stress divided by that at rest. Results: The T1 values at rest were significantly higher in HCM than control (1245±9ms vs. 1196±11ms, p=0.0027), and the T1 values after adenosine stress significantly increased in both groups (HCM: 1285±10ms, p=0.0018 vs. rest, control: 1244±9ms, p=0.0128 vs. rest, Figure 1). Both IVS and LVFW demonstrated significantly lower ΔT1 in HCM than control (IVS: 3.95±0.35% vs. 5.68±0.41%, p=0.0163, LVFW: 4.80±0.39% vs. 6.75±0.65%, p=0.0163, Figure 2). CFR in HCM significantly decreased than that in control (2.48±0.40 % vs. 5.97±1.31 %, p=0.0051). Multiple regression analysis revealed that ΔT1 of both IVS and LVFW was correlated with CFR (β=0.527, p=0.0026, β=0.445, p=0.0325). Conclusions: T1 reactivity significantly decreased in both nonhypertrophied and hypertrophied myocardium of HCM compared to control. Stress T1 mapping have the advantage of being able to estimate regional CMD in addition to global CMD.