Assessment Of Microvascular Function Research Articles

Impaired systemic microvascular function in patients with resistant arterial hypertension and microalbuminuria: an observational study

Abstract Background Systemic arterial hypertension (SAH) is one of the most prevalent diseases worldwide and is known to be associated with alterations of microvascular function. It is well known that microalbuminuria (MAU) is considered an early marker of renal and cardiac injury in SAH and is an independent risk factor for cardiovascular events in this population. Additionally, it is associated with altered endothelial function, which occurs from the early stages and can be considered an early marker. In some cases, SAH presents as resistant arterial hypertension (RAH), resulting in a worse prognosis compared to individuals with non-resistant hypertension. Moreover, MAU is associated with higher mortality, independent of glomerular filtration rate. Endothelial dysfunction is also a risk marker found in different conditions and can add to MAU in patients with RAH. Purpose To investigate systemic microvascular function in patients with RAH, with or without MAU. Methods 64 patients with RAH, of both genders (50% men), were evaluated, with 32 having MAU and 32 without MAU (defined as a urinary albumin/creatinine ratio between 30 and 300 mg/g in a routine urine sample). Microvascular function assessment was performed using a laser speckle system, allowing analysis of cutaneous microvascular flow. Flow measurements were expressed in arbitrary perfusion units (APU) divided by the mean arterial pressure to obtain cutaneous vascular conductance (CVC). A post-occlusive reactive hyperemia (PORH) test was performed, with brachial artery occlusion using a sphygmomanometer 50 mmHg above systolic pressure for 3 minutes; cutaneous flow was measured after release of the occlusion. Results Patients with or without MAU did not differ in terms of age, frequency of diabetes, and chronic kidney disease. The peak CVC values during PORH were 0.64 ± 0.15 and 0.55 ± 0.15 APU/mmHg in RH and RH + MAU patients, respectively (P=0.03). The delta values (peak – baseline) during PORH were 0.31 ± 0.11 and 0.25 ± 0.09 APU/mmHg in RH and RH + MAU patients, respectively (P=0.04)(Figure 1). Conclusions PORH-induced vasodilation was found to be reduced in patients with RAH and MAU compared to patients without MAU. This finding shows alteration of endothelium-dependent vasodilation mechanisms in these patients, indicating reduced systemic microvascular endothelial function. Endothelial dysfunction may be associated with glomerular permeability changes, contributing to MAU and further increasing the risk for these patients. This suggests the need for more intensive therapeutic interventions and better risk stratification for these patients, as endothelial dysfunction can be found in the early stages of the disease.Figure 1

Assessment of coronary microvascular function with absolute coronary fl ow measurements

Abstract Background Reliable assessment of microvascular function is essential, both in research setting and clinical practice. New techniques, such as continuous coronary thermodilution, are very promising and could revolutionize the field. However, there is a need for proper validation before widespread use is possible. Purpose The goals of this study were: 1. to validate the potential of saline infusion to generate maximum hyperemia in vivo. 2. to validate absolute blood flow (ABF) measured with continuous coronary thermodilution at higher (40-50 ml/min) infusion speeds 3. To assess the safety of higher infusion speeds. Methods Fourteen closed-chest sheep underwent ABF measurements with increasing saline infusion speeds with and without adenosine. Another seven open-chest sheep underwent these measurements with epicardial doppler flow probes on both the left anterior descending artery and left circumflex coronary artery. Maximal hyperemia was defined as maximal flow after 45 seconds of proximal occlusion. The principles of laboratory animal care and all national regulations were followed. Results 20 ml/min of saline infusion induced lower hyperemic coronary flow (140 vs 191 ml/min, p=0.0165) and lower coronary flow reserve (CFR) (1.82 vs 3.21, p= <0.0001) than coronary occlusion. In contrast, 30 ml/min resulted in flow (196 vs 192 ml/min, p=0.8292) and CFR (2.77 vs 3.21, p=0.1107) that were not different from post-occlusion. There was a significant flow overestimation bias (Bland-Altman: Bias ± SD: -73.09 ± 30.52, 95% Limits of agreement: -132.9 to -13.27) with 40-50ml/min of saline. Occasionally, higher saline infusion rates resulted in ischemic ECG-changes and ventricular fibrillation (9.5% at 50 ml/min). Conclusions Continuous saline infusion of 30ml/min, but not 20 ml/min, induced maximal hyperemia. ABF measured with saline infusion speeds of 40-50 ml/min was not accurate nor safe, and should therefore be avoided.

Absolute coronary blood flow across different endotypes of ANOCA.

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

Assessment of Microvascular Function Based on Flowmotion Monitored by the Flow-Mediated Skin Fluorescence Technique.

This review summarizes studies dedicated to the assessment of microvascular function based on microcirculatory oscillations monitored by the Flow-Mediated Skin Fluorescence (FMSF) technique. Two approaches are presented. The first approach uses oscillatory parameters measured under normoxic conditions, expressed as flowmotion (FM), vasomotion (VM), and the normoxia oscillatory index (NOI). These parameters have been used for the identification of impaired microcirculatory oscillations associated with intense physical exercise, post-COVID syndrome, psychological stress, and erectile dysfunction. The second approach involves characterization of the microcirculatory response to hypoxia based on the measurement of hypoxia sensitivity (HS). The HS parameter is used to characterize microvascular complications in diabetes, such as diabetic kidney disease and diabetic foot ulcers. Based on research conducted by the authors of this review, the FMSF parameter ranges characterizing microvascular function are presented. The diagnostic approach to assessing microvascular function based on flowmotion monitored by the FMSF technique has a wide range of applications and the potential to be integrated into widespread medical practice.

Pilot Assessment of Piezoelectric Transducers as a Cost-Effective Alternative to EndoPAT

Introduction: Current microvascular assessments may not be practical or accessible requiring experienced personnel and/or ongoing equipment costs. Piezoelectric transducers can reliably obtain finger blood pressure waves, similar to peripheral arterial tonometry devices; thus, they could be used to estimate microvascular function. We aimed to validate piezoelectric transducers as an alternative measure of microvascular function compared to EndoPAT. Methods: Twenty-five adults (aged 20–64 years) completed reactive hyperemia (5 min forearm circulatory occlusion and 3 min recovery) with piezoelectric transducers on the middle fingers and EndoPAT probes on the index fingers. Average area under the curve (AUC) of the pulse wave signal for the occluded and control arms was determined at baseline, every 30 s post-occlusion, and 10 s around the peak response. Microvascular function index (MFI) was calculated as the ratio of AUC post-occlusion to AUC baseline in the test arm, then normalized to the same ratio in the control arm. MFI at each time point was correlated with the reactive hyperemia index (RHI) from the EndoPAT. Results: The greatest significance was found between RHI and MFI at 10 s around the peak response (Spearman’s r = 0.67, p = 0.0002; Pearson’s r = 0.76, p = 0.00001). Conclusion: MFI is a reusable and user-friendly microvascular function assessment that could provide better access to vascular health screening.

Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation

BackgroundCoronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients. MethodThis study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis. ResultA total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR>39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank P < 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529–6.418; P < 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P < 0.001) and no catheter ablation (log-rank P < 0.001). ConclusionElevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.

Coronary Microvascular Function Assessment using the Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Studies reporting the status of coronary microvascular function in the infarct-related artery (IRA) after primary percutaneous coronary intervention (PCI) remain limited. This study utilized the coronary angiography-derived index of microcirculatory resistance (caIMR) to assess coronary microvascular function in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. We used the FlashAngio system to measure the caIMR after primary PCI in 157 patients with STEMI. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite endpoint encompassing cardiac mortality, target vessel revascularization, and rehospitalization due to congestive heart failure (CHF), myocardial infarction (MI), or angina. Approximately 30% of patients diagnosed with STEMI and who experienced successful primary PCI during the study period had a caIMR in the IRA of 40. The caIMR in the IRA was significantly higher than in the reference vessel (32.9 15.8 vs. 27.4 11.1, p 0.001). The caIMR in the reference vessel of the caIMR 40 group was greater than in the caIMR 40 group (30.9 11.3 vs. 25.9 10.7, p = 0.009). Moreover, the caIMR 40 group had higher incidence rates of MACEs at 3 months (25.5% vs. 8.3%, p = 0.009) and 1 year (29.8% vs. 13.9%, p = 0.04), than in the caIMR 40 group, which were mainly driven by a higher rate of rehospitalization due to CHF, MI, or angina. A caIMR in the IRA of 40 was an independent predictor of a MACE at 3 months (hazard ratio (HR): 3.459, 95% confidence interval (CI): 1.363-8.779, p = 0.009) and 1 year (HR: 2.384, 95% CI: 1.100-5.166, p = 0.03) in patients with STEMI after primary PCI. Patients with STEMI after primary PCI often have coronary microvascular dysfunction, which is indicated by an increased caIMR in the IRA. An elevated caIMR of 40 in the IRA was associated with an increased risk of adverse outcomes in STEMI patients undergoing primary PCI.

Abstract 17076: The Relationship Between Impaired Microvascular Function, Cardiovascular Risk Profile and Subclinical Atherosclerotic Burden in a Swedish Middle-Aged Cohort

Introduction: Microvascular function is associated with cardiovascular risk factors and deteriorates in individuals with cardiovascular disease. Hypothesis: The aim of this study was to investigate the relationship between microvascular function, cardiovascular risk profile and subclinical atherosclerotic burden. Methods: The study enrolled 3809 randomly selected individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study (SCAPIS). Microvascular function was measured in forearm skin using an arterial occlusion and release protocol determining the peak blood oxygen saturation, OxyP. Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation (SCORE2; 10-year risk of fatal and non-fatal CVD events). OxyP was compared with Coronary artery calcification score (CACS) and plaques in the carotid arteries. Results: Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function), had a mean SCORE2 of 5.8% compared to 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. In the low-risk SCORE2 level (&lt;5% risk), 19.0% of the individuals have impaired microvascular function as compared to 48.1% in the high-risk SCORE2 level (&gt;10% risk). OxyP was lower in individuals with coronary artery calcification (CACS&gt;0) and those with both carotid plaque and CACS&gt;0, as compared to individuals without subclinical atherosclerotic burden (CACS=0 and no carotid plaque; 87.5 ±5.6 % and 86.9 ±6.0 % vs 88.6 ± 5.8 %, p &lt; 0.01). Conclusion: In a population without cardiovascular disease or diabetes mellitus, impaired microvascular function is associated with higher SCORE2 risk and CACS&gt;0. Hence, assessment of microvascular function may be a useful tool for accurate cardiovascular risk prediction, in addition to imaging assessment of atherosclerosis in the coronary and carotid arteries.

The relationships between acetylcholine-induced chest pain, objective measures of coronary vascular function and symptom status.

Acetylcholine-induced chest pain is routinely measured during the assessment of microvascular function. The aim was to determine the relationships between acetylcholine-induced chest pain and both symptom burden and objective measures of vascular function. In patients with angina but no obstructive coronary artery disease, invasive studies determined the presence or absence of chest pain during both acetylcholine and adenosine infusion. Thermodilution-derived coronary blood flow (CBF) and index of microvascular resistance (IMR) was determined at rest and during both acetylcholine and adenosine infusion. Patients with epicardial spasm (>90%) were excluded; vasoconstriction between 20% and 90% was considered endothelial dysfunction. Eighty-seven patients met the inclusion criteria. Of these 52 patients (60%) experienced chest pain during acetylcholine while 35 (40%) did not. Those with acetylcholine-induced chest pain demonstrated: (1) Increased CBF at rest (1.6 ± 0.7 vs. 1.2 ± 0.4, p = 0.004) (2) Decreased IMR with acetylcholine (acetylcholine-IMR = 29.7 ± 16.3 vs. 40.4 ± 17.1, p = 0.004), (3) Equivalent IMR following adenosine (Adenosine-IMR: 21.1 ± 10.7 vs. 21.8 ± 8.2, p = 0.76), (4) Increased adenosine-induced chest pain (40/52 = 77% vs. 7/35 = 20%, p < 0.0001), (5) Increased chest pain during exercise testing (30/46 = 63% vs. 4/29 = 12%, p < 0.00001) with no differences in exercise duration or electrocardiographic changes, and (6) Increased prevalence of epicardial endothelial dysfunction (33/52 = 63% vs. 14/35 = 40%, p = 0.03). After excluding epicardial spasm, acetylcholine-induced chest pain is associated with increased pain during exercise and adenosine infusion, increased coronary blood flow at rest, decreased microvascular resistance in response to acetylcholine and increased prevalence of epicardial endothelial dysfunction. These findings raise questions about the mechanisms underlying acetylcholine-induced chest pain.

Microvascular Health is Reduced in Frequent Cannabis Users

BACKGROUND: Microvascular dysfunction is a marker of endothelial vascular damage and is considered one of the earliest indicators of cardiovascular disease (CVD) development. Frequent cannabis use has been previously linked to increased CVD risk. However, whether microvascular health is impacted by cannabis use in otherwise healthy young adults has not been explored yet. PURPOSE: The purpose of this study was to investigate the impact of frequent cannabis usage on microvascular health in young healthy adults. METHODS: Thirteen frequent cannabis users (CU, 5 males and 8 females; age:23±3 yo; used cannabis 2.5±2 days/week) and thirteen demographical matched never users (NU, 5 males and 8 females; age:22±1 yo) completed a comprehensive assessment of microvascular function. Microvascular health was assessed using Laser Doppler Imaging coupled with Post Occlusive Reactive Hyperemia (PORH), to evaluate overall microvascular function, and Local Thermal Hyperemia (LTH) to evaluate neurogenic and endothelial mechanisms of vascular function. Blood flow was calculated as cutaneous vascular conductance, considering red blood cell flux and mean arterial blood pressure. RESULTS: Cannabis users exhibited significantly ( p=0.01) lower microvascular function when compared to never users (PORH, CU: 0.68±0.18 vs. NU: 0.85±0.14 mmHg/PU). Of note, microvascular function was significantly ( p=0.03) reduced in those that use cannabis more than 2.5 days/week (n=5; 0.55±0.10) when compared to those who used it less frequently (n=8; 0.76±0.18 mmHg/PU). In addition, neurogenic mechanisms (CU:1.31±0.57 vs. NU: 1.89±0.48 mmHg/PU; p=0.009) and endothelial mechanisms (CU: 1.61±0.44 vs. NU: 1.96±0.35 mmHg/PU; p=0.03) were significantly lower in cannabis users when compared to never users. CONCLUSIONS: Our results suggest that frequent cannabis users exhibit reduced microvascular health in comparison to never users, suggesting worse long-term CVD outcomes. Specifically, those that use cannabis more than 2 times per week exhibit lower microvascular function. In addition, cannabis use negatively impact neurogenic and endothelial microvascular mechanisms that warrant further investigation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical implications of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease and role of the thermodilution method.

More than 60% of patients undergoing coronary angiography present no coronary artery disease (CAD). Angina and myocardial ischemia are classically determined by epicardial vascular obstruction, but coronary microvascular dysfunction (CMD) may also represent a possible cause for these phenomena. Two endotypes of CMD have been recognized, with two different pathophysiological mechanisms: structural CMD, characterized by low coronary flow reserve (CFR) and high microvascular resistance (MVR) values; and functional CMD, characterized by low CFR and normal MVR values. According to the present data, almost half of patients with non-obstructive CAD have shown signs of CMD. For this reason, further investigations for microvascular function assessment should be considered when evaluating no-CAD patients complaining of angina or presenting signs of myocardial ischemia. The thermodilution method is currently becoming a widespread invasive technique due to its feasibility and high reproducibility for coronary physiology evaluation. Furthermore, a recently introduced technique - called continuous thermodilution - allows for direct measurement of absolute coronary flow and resistances. The role of this brand-new technique in the clinical scenario is however still to be fully investigated and its use is at present limited to research purposes only. Among no-CAD patients, both structural and functional CMD are related to a worse prognosis in term of mortality and major adverse cardiovascular events (MACE). In this review, we will discuss the present evidence supporting the definition, prevalence and clinical implication of the different forms of CMD and the technical aspects of its invasive assessment.

Design and rationale of the NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT)

BackgroundAngina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands. MethodsThe NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered.The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee. ConclusionNL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.

6 EVALUATION OF ECHOCARDIOGRAPHIC PARAMETERS IN PATIENTS WITH MICROVASCULAR DYSFUNCTION: A PROSPECTIVE STUDY.

Abstract Background The prevalence of microvascular angina is underestimated in the general population because it is often difficult to detect. Microvascular dysfunction is defined by parameters of reduced coronary flow reserve (CFR &amp;lt;2) without epicardial stenosis and/or increased index of microvascular resistance (IMR&amp;gt; 25). Purpose The aim of this study was to evaluate the echocardiographic parameters in patients with symptoms of myocardial ischemia without evident coronary epicardial obstruction. Primary endpoint was to analyze the global longitudinal strain of the left ventricle and the left atria strain in patients with microvascular angina. Secondary endpoint was to analyze echocardiographic parameters to evaluate the diastolic function of the left ventricle, the prevalence of cardiovascular risk factors and the blood tests values. Methods Between 1st February 2019 and 1st May 2022, subjects with angina and not functionally significant epicardial stenosis (Resting Full-cycle Ratio &amp;gt; 0.91, Fractional flow reserve &amp;gt;0.80), underwent assessment of microvascular function and were divided into 2 cohorts. All patients had sinus rhythm, preserved left ventricular ejection fraction (LVEF&amp;gt; 55%), no severe left ventricular hypertrophy (interventricular septum &amp;lt;13 mm) or structural heart disease. For each patient we analyzed the left ventricular global longitudinal strain in the three apical views (4 chamber, 2 chamber and 3 chamber) and the left atria strain, PALS (peak atrial longitudinal strain) and PACS (peak atrial contraction strain), in two apical views (4 chamber and 2 chamber). We also measured the diastolic function indices (E/e’, isovolumic relaxation time, deceleration time), the left atrial area and pulmonary artery systolic pressure (PASP) evaluated on echocardiography. Results A total of 132 patients were enrolled. Of those, 47 had evidence of microvascular dysfunction and 85 had normal CFR/IMR. Primary Endpoint: patients with microvascular dysfunction had reduced values of left ventricular global longitudinal strain and reduced values of left atrial strain compared to controls (p&amp;lt;0,001). Secondary Endpoint: a higher prevalence of diabetic and obese women was associated with microvascular dysfunction. However, there were no significant differences in age, prevalence of hypertension, dyslipidemia, smoking and dysthyroidism. Numerically higher values of NTproB-type Natriuretic Peptide (NTproBNP) and C-reactive protein were seen in patients with microvascular dysfunction, while there were no significant differences in hemoglobin, white bold cells, platelets, cholesterol, creatinine and troponin values. Left ventricular isovolumic relaxation time, left atrium area, and pulmonary artery systolic pressure as well as E/e' values were significantly increased in patients with microvascular dysfunction. Furthermore, there was a significant reduction in deceleration time values. Conclusion Patient with microvascular dysfunction are frequently diabetic and obese women. Echocardiographic parameters show left ventricular diastolic dysfunction and possibly subsequent left atrial remodeling. Furthermore, the analysis of the global longitudinal strain of the left ventricle could reveal alterations in cardiac contractile mechanics that are difficult to identify with conventional echocardiography. NTproBNP values were not significantly higher, demonstrating that patients with microvascular dysfunction have an early diastolic dysfunction that is not clinically evident.

Assessment of microvascular function using a novel technique Flow Mediated Skin Fluorescence (FMSF) in patients with diabetic kidney disease: A preliminary study.

Diabetic kidney disease (DKD) plays an important role in morbidity and mortality in patients with diabetes mellitus. The pathogenesis of this microangiopathy is mainly due to impaired vascular endothelial function. The Flow Mediated Skin Fluorescence (FMSF) method is an innovative, non-invasive tool for assessing the microcirculation function (especially microcirculatory response to hypoxia), also in patients with complications of diabetes mellitus (DM). The study was conducted at the Medical University of Lodz, Poland. Total of 84 volunteers including 30 patients with DKD, 33 patients with DM without complications, and 21 healthy subjects underwent microvascular function assessments using FMSF. This technique measures changes in the intensity of nicotinamide adenine dinucleotide (NADH) fluorescence from the skin on the forearm as a function of time, in response to blocking and releasing blood flow in the forearm. In this study we asses two key parameters: Reactive Hyperemia Response (RHR) and Hypoxia Sensitivity [log(HS)] to characterize vascular circulation in patients with DKD and their response to transient ischemia. The patients with low reactive hyperemic response (the RHR parameter) had a significantly higher sCr than patients with moderate and high RHR value (p<0.001, p<0.05, respectively) and a significantly lower eGFR than the patients with moderate and high RHR parameter (p<0.001, p<0.01, respectively). The patients with very low and low log(HS) values had a significantly higher sCr than the patients with high log(HS) (p<0.001, p<0.01, respectively), and a significantly lower eGFR than the patients with high log(HS) parameter (p<0.001, p<0.01, respectively). The patients with very low log(HS) had a significantly higher sCr and a significantly lower eGFR than the patients with moderate (p<0.05, p<0.01, respectively). The mean value of the RHR parameter was significantly lower in DKD patients (18.31±5.06%) compared to both healthy subjects (34.37±8.18%, p<0.001) and DM without complications subgroup (28.75±7.12%, p<0.001). Similar trends were noted with the mean value of log(HS) parameter in DKD subgroup (1.03±0.5) vs. healthy subjects (1.59±0.53, p<0.001), and vs. DM without complications subgroup (1.73±0.52, p<0.001). We observed a significant inverse correlation between the RHR parameter and serum creatinine (sCr) and a significant positive correlations with eGFR (R= -0.3; p<0.05, R=0.61; p<0.001, respectively). We found also a significant negative correlations of the log(HS) measure with sCr and a significant positive correlations with eGFR (R=-0.33; p<0.01, R=0.55; p<0.001, respectively). We observed also a significant inverse correlation between the RHR and log(HS) parameters and advanced glycation end products (AGEs) (R=-0.6; p<0.001, R=-0.32; p<0.01, respectively). The AGEs parameter was also a significantly higher in patients with low RHR parameter than in patients with moderate (p<0.01) and high (p<0.001). The FMSF technique makes it possible to identify impairments of the microvascular function in patients with DKD. This study confirms that the simple two-parametric approach diagnostic tool perfectly characterizes the state of the microvascular system in diabetic patients with impaired renal function. These preliminary results require further validation in a larger patients cohort.

Microvascular dysfunction in patients with diabetes mellitus: assessment of absolute coronary flow and microvascular resistance reserve

Abstract Background Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of systolic and diastolic dysfunction (DDF). Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic versus non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of DDF was compared between the two groups. Methods In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results The median FFR value was 0.83 [0.79–0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR=2.4±0.6 and 2.9±0.8; MRR=2.8±0.9 and 3.5±1 for diabetic and non-diabetic patients respectively, [p&amp;lt;0.05 for both], Figure 1 and 2). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p&amp;lt;0.05). Conclusions Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical DDF associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease. 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

Role of different echocardiographic modalities in the assessment of microvascular function in women with ischemia and no obstructive coronary arteries.

This review summarizes current knowledge about echocardiographic modalities used to assess microvascular function and left ventricular (LV) systolic function in women with ischemia and no obstructive coronary arteries (INOCA). Although the entire pathophysiological background of this clinical entity still remains elusive, it is primarily linked to microvascular dysfunction which can be assessed by coronary flow velocity reserve. Subtle impairments of LV systolic function in women with INOCA are difficult to assess by interpretation of wall motion abnormalities. LV longitudinal function impairment is considered to be an early marker of subclinical systolic dysfunction and can be assessed by global longitudinal strain quantification.

Reliability of the passive leg movement assessment of vascular function in men.

What is the central question of this study? Use of the passive leg movement (PLM) test, a non-invasive assessment of microvascular function, is on the rise. However, PLM reliability in men has not been adequately investigated, nor has such reliability data, in men, been compared to the most commonly employed vascular function assessment, flow-mediated vasodilation (FMD). What is the main finding and its importance? PLM is a reliable method to assess vascular function in men, and is comparable to values previously reported for PLM in women, and for FMD. Given the importance of vascular function as a predictor of cardiovascular disease risk, these data support the utility of PLM as a clinically relevant measurement. Although vascular function is an independent predictor of cardiovascular disease risk, and therefore has significant prognostic value, there is currently not a single clinically accepted method of assessment. The passive leg movement (PLM) assessment predominantly reflects microvascular endothelium-dependent vasodilation and can identify decrements in vascular function with advancing age and pathology. Reliability of the PLM model was only recently determined in women, and has not been adequately investigated in men. Twenty healthy men (age: 27±2year) were studied on three separate experimental days, resulting in three within-day and three between-day trials. The hyperemic response to PLM was assessed with Doppler ultrasound, and expressed as the absolute peak in leg blood flow (LBFpeak ), change from baseline to peak (ΔLBFpeak ), absolute area under the curve (LBFAUC ), and change in AUC from baseline (ΔLBFAUC ). PLM-induced hyperemia yielded within-day coefficients of variation (CV) from 10.9 to 22.9%, intraclass correlation coefficients (ICC) from 0.82 to 0.90, standard error of the measurement (SEM) from 8.3 to 17.2%, and Pearson's correlation coefficients (r) from 0.56 to 0.81. Between-day assessments of PLM hyperemia resulted in CV from 14.4 to 25%, ICC from 0.75 to 0.87, SEM from 9.8 to 19.8%, and r from 0.46 to 0.75. Similar to previous reports in women, the hyperemic responses to PLM in men display moderate-to-high reliability, and are comparable to reliability data for brachial artery flow mediated vasodilation. These positive reliability findings further support the utility of PLM as a clinical measurement of vascular function and cardiovascular disease risk.

Assessment of Microvascular Function Using a Novel Technique Flow Mediated Skin Fluorescence (FMSF) in Patients with Diabetic Kidney Disease: A Preliminary Study

Assessment of Microvascular Function Using a Novel Technique Flow Mediated Skin Fluorescence (FMSF) in Patients with Diabetic Kidney Disease: A Preliminary Study

389 Microvascular dysfunction in patients with Type II diabetes mellitus: invasive assessment of absolute coronary blood flow and microvascular resistance reserve

Abstract Aims Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups. Methods In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperaemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results The median FFR value was 0.83 (0.79–0.87) without any significant difference between the two groups. Absolute resting and hyperaemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperaemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group [CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, (P &amp;lt; 0.05 for both)]. Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all P &amp;lt; 0.05). Conclusions Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperaemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.