Coronary Microvascular Resistance Research Articles

Repeatability of bolus and continuous thermodilution for assessing coronary microvasculatory function

Abstract Introduction The bolus thermodilution-derived index of microcirculatory resistance (IMR) has emerged over years as the standard of reference to invasively define coronary microvascular dysfunction (CMD). However, the technique still presents some limitations, mainly related to the fact that manual injection of saline bolus accounts for some variance in the measurements. Continuous intracoronary thermodilution has been recently introduced as a tool to directly quantify absolute coronary flow and microvascular resistance both at rest and during hyperemia and has shown to be safe and operator independent. Microvascular resistance reserve (MRR), derived from continuous thermodilution, has been validated as novel index specific for microcirculation and independent from myocardial mass. Purpose To compare head-to-head the intra-observer repeatability of bolus and continuous thermodilution for assessing microvascular function. Methods Patients undergoing coronary angiography in the absence of obstructive coronary artery disease were prospectively enrolled. Bolus and continuous intracoronary thermodilution measurements were performed in duplicates in the left anterior descending artery (LAD). Patients were randomly assigned in a 1:1 ratio to undergo first bolus thermodilution or first continuous thermodilution assessment. Results A total of 102 patients were enrolled. Average FFR was 0.86±0.06. Coronary Flow Reserve (CFR) calculated with continuous thermodilution (CFRthermo) was significantly lower than bolus thermodilution-derived CFR (CFRbolus) (2.63±0.65 and 3.29±1.17, respectively, p<0.001). CFRthermo showed a lower variability and a higher agreement than CFRbolus (variability 12.74±10.41% vs 31.26±24.85%, respectively, p<0.001; ICC= 0.78 (0.70–0.85) and 0.48 (0.32–0.62), respectively, p<0.001, Figure 1). Both MRR and IMR showed a good agreement (ICC 0.81 (0.74–0.87) and 0.80 (0.71–0.86)) but the variability of the MRR was significantly lower (12.44±10.06% vs 24.24±19.27, respectively, p<0.001, Figure 1). Reproducibility data of all indices derived from duplicated measurements of bolus and continuous thermodilution are reported in Table 2. Conclusion Continuous intracoronary thermodilution has a higher repeatability than bolus thermodilution in the assessment of CMD. Funding Acknowledgement Type of funding sources: None.

Machine learning assisted reflectance spectral characterisation of coronary thrombi correlates with microvascular injury in patients with ST-segment elevation acute coronary syndrome.

AimsWe set out to further develop reflectance spectroscopy for the characterisation and quantification of coronary thrombi. Additionally, we explore the potential of our approach for use as a risk stratification tool by exploring the relation of reflectance spectra to indices of coronary microvascular injury.Methods and resultsWe performed hyperspectral imaging of coronary thrombi aspirated from 306 patients presenting with ST-segment elevation acute coronary syndrome (STEACS). Spatially resolved reflected light spectra were analysed using unsupervised machine learning approaches. Invasive [index of coronary microvascular resistance (IMR)] and non-invasive [microvascular obstruction (MVO) at cardiac magnetic resonance imaging] indices of coronary microvascular injury were measured in a sub-cohort of 36 patients. The derived spectral signatures of coronary thrombi were correlated with both invasive and non-invasive indices of coronary microvascular injury. Successful machine-learning-based classification of the various thrombus image components, including differentiation between blood and thrombus, was achieved when classifying the pixel spectra into 11 groups. Fitting of the spectra to basis spectra recorded for separated blood components confirmed excellent correlation with visually inspected thrombi. In the 36 patients who underwent successful thrombectomy, spectral signatures were found to correlate well with the index of microcirculatory resistance and microvascular obstruction; R2: 0.80, p < 0.0001, n = 21 and R2: 0.64, p = 0.02, n = 17, respectively.ConclusionMachine learning assisted reflectance spectral analysis can provide a measure of thrombus composition and evaluate coronary microvascular injury in patients with STEACS. Future work will further validate its deployment as a point-of-care diagnostic and risk stratification tool for STEACS care.

Incorporating clinical parameters to improve the accuracy of angiography-derived computed fractional flow reserve.

Angiography-derived fractional flow reserve (angio-FFR) permits physiological lesion assessment without the need for an invasive pressure wire or induction of hyperaemia. However, accuracy is limited by assumptions made when defining the distal boundary, namely coronary microvascular resistance (CMVR). We sought to determine whether machine learning (ML) techniques could provide a patient-specific estimate of CMVR and therefore improve the accuracy of angio-FFR. Patients with chronic coronary syndromes underwent coronary angiography with FFR assessment. Vessel-specific CMVR was computed using a three-dimensional computational fluid dynamics simulation with invasively measured proximal and distal pressures applied as boundary conditions. Predictive models were created using non-linear autoregressive moving average with exogenous input (NARMAX) modelling with computed CMVR as the dependent variable. Angio-FFR (VIRTUheart™) was computed using previously described methods. Three simulations were run: using a generic CMVR value (Model A); using ML-predicted CMVR based upon simple clinical data (Model B); and using ML-predicted CMVR also incorporating echocardiographic data (Model C). The diagnostic (FFR ≤ or >0.80) and absolute accuracies of these models were compared. Eighty-four patients underwent coronary angiography with FFR assessment in 157 vessels. The mean measured FFR was 0.79 (±0.15). The diagnostic and absolute accuracies of each personalized model were: (A) 73% and ±0.10; (B) 81% and ±0.07; and (C) 89% and ±0.05, P < 0.001. The accuracy of angio-FFR was dependent in part upon CMVR estimation. Personalization of CMVR from standard clinical data resulted in a significant reduction in angio-FFR error.

Absolute coronary flow and microvascular resistance reserve in patients with severe aortic stenosis

BackgroundDevelopment of left ventricle (LV) hypertrophy in aortic stenosis (AS) is accompanied by adaptive coronary flow regulation. We aimed to assess absolute coronary flow, microvascular resistance, coronary flow reverse (CFR)...

Simulating Stenotic Conditions of the Coronary Artery in a Lumped Parameter Model of the Cardiovascular System.

Coronary flow control mechanisms maintain the average coronary blood flow (CBF) at 4% of the cardiac output (CO) in normal adults, with no prior diagnosis of coronary artery disease (CAD), under resting conditions. This paper explores a pulsatile sixth order lumped parameter (LP) model of the cardiovascular system (CVS) which utilizes the average CBF approximated from CO along with arterial blood pressure (ABP) waveform to estimate the coronary microvascular resistance using non-linear least square optimization technique. The CVS model includes a third order model of the coronary vascular bed and is shown to achieve phasic coronary flow. The coronary epicardial resistance is varied to emulate different degrees of stenosis and achieve realistic behavior of coronary microvascular resistance under these conditions.

The Complementary Value of Absolute Coronary Flow in the Assessment of Patients with Ischaemic Heart Disease

Fractional flow reserve (FFR) is the current gold standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown. In this study, we compared fractional CBF with absolute CBF (aCBF, in ml min−1), measured with a computational method during standard angiography and pressure wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r = 0.89 and Cohen’s kappa = 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%) but reduced when FFR was ≤0.80 (81%), 0.70–0.80 (68%) and, particularly, 0.75–0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR and may be valuable to assess CBF, particularly in cases within the FFR ‘gray zone’.

Coronary Flow Evaluation in Heart Transplant Patients Compared to Healthy Controls Documents the Superiority of Coronary Flow Velocity Reserve Companion as Diagnostic and Prognostic Tool.

BackgroundDistinct contributions by functional or structural alterations of coronary microcirculation in heart transplantation (HT) and their prognostic role have not been fully elucidated. We aimed to identify the mechanisms of coronary microvascular dysfunction (CMD) in HT and their prognostic implications.Methods134 patients, surviving at least 5 years after HT, without evidence of angiographic vasculopathy or symptoms/signs of rejection were included. 50 healthy volunteers served as controls. All underwent the assessment of rest and hyperemic coronary diastolic peak flow velocity (DPVr and DPVh) and coronary flow velocity reserve (CFVR) and its inherent companion that is based on the adjusted quadratic mean: CCFVR = √{(DPVr)2 + (DPVh)2}. Additionally, basal and hyperemic coronary microvascular resistance (BMR and HMR) were estimated.ResultsBased on CFVR and DPVh, HT patients can be assigned to four endotypes: endotype 1, discordant with preserved CFVR (3.1 ± 0.4); endotype 2, concordant with preserved CFVR (3.4 ± 0.5); endotype 3, concordant with impaired CFVR (1.8 ± 0.3) and endotype 4, discordant with impaired CFVR (2.0 ± 0.2). Intriguingly, endotype 1 showed lower DPVr (p < 0.0001) and lower DPVh (p < 0.0001) than controls with lower CFVR (p < 0.0001) and lower CCFVR (p < 0.0001) than controls. Moreover, both BMR and HMR were higher in endotype 1 than in controls (p = 0.001 and p < 0.0001, respectively), suggesting structural microvascular remodeling. Conversely, endotype 2 was comparable to controls. A 13/32 (41%) patients in endotype 1 died in a follow up of 28 years and mortality rate was comparable to endotype 3 (14/31, 45%). However, CCFVR was < 80 cm/s in all 13 deaths of endotype 1 (characterized by preserved CFVR). At multivariable analysis, CMD, DPVh < 75 cm/s and CCFVR < 80 cm/s were independent predictors of mortality. The inclusion of CCFVR < 80 cm/s to models with clinical indicators of mortality better predicted survival, compared to only adding CMD or DPVh < 75 cm/s (p < 0.0001 and p = 0.03, respectively).ConclusionA normal CFVR could hide detection of microvasculopathy with high flow resistance and low flow velocities at rest. This microvasculopathy seems to be secondary to factors unrelated to HT (less rejections and more often diabetes). The combined use of CFVR and CCFVR provides more complete clinical and prognostic information on coronary microvasculopathy in HT.

Automation of intracoronary continuous thermodilution for absolute coronary flow and microvascular resistance measurements.

Microvascular resistance reserve (MRR) as derived from continuous intracoronary thermodilution specifically quantifies microvasculature function. As originally described, the technique necessitates reinstrumentation of the artery and manual reprogramming of the infusion pump when performing resting and hyperemic measurements. To simplify and to render this procedure operator-independent, we developed a fully automated method. The aim of the present study is to validate the automated procedure against the originally described one. For the automated procedure, an infusion pump was preprogrammed to allow paired resting-hyperemic thermodilution assessment without interruption. To validate the accuracy of this new approach, 20automated measurements were compared to those obtained in the same vessels with conventional paired resting-hyperemic thermodilution measurements (i.e., with a sensor pullback at each infusion rate and manual reprogramming of the infusion pump). A close correlation between the conventional and the automated measuring technique was found for resting flow (Qrest : r = 0.89, mean bias = 2.52; SD = 15.47), hyperemic flow (Qhyper : r = 0.88, mean bias = -2.65; SD = 27.96), resting microvascular resistance (Rμ-rest : r = 0.90, mean bias = 52.14; SD = 228.29), hyperemic microvascular resistance Rμ-hyper : r = 0.92, mean bias = 12.95; SD = 57.80), and MRR (MRR: r = 0.89, mean bias = 0.04, SD = 0.59). Procedural time was significantly shorter with the automated method (5'25″ ± 1'23″vs. 4'36″ ± 0'33″, p = 0.013). Continuous intracoronary thermodilution-derived measurements of absolute flow, absolute resistance, and MRR can be fully automated. This further shortens and simplifies the procedure when performing paired resting-hyperemic measurements.

Microcirculatory Function in Nonhypertrophic and Hypertrophic Myocardium in Patients With Aortic Valve Stenosis.

BackgroundLeft ventricular hypertrophy (LVH) has often been supposed to be associated with abnormal myocardial blood flow and resistance. The aim of this study was to evaluate and quantify the physiological and pathological changes in myocardial blood flow and microcirculatory resistance in patients with and without LVH attributable to severe aortic stenosis.Methods and ResultsAbsolute coronary blood flow and microvascular resistance were measured using a novel technique with continuous thermodilution and infusion of saline. In addition, myocardial mass was assessed with cardiac magnetic resonance imaging. Fifty‐three patients with aortic valve stenosis were enrolled in the study. In 32 patients with LVH, hyperemic blood flow per gram of tissue was significantly decreased compared with 21 patients without LVH (1.26±0.48 versus 1.66±0.65 mL·min−1·g−1; P=0.018), whereas minimal resistance indexed for left ventricular mass was significantly increased in patients with LVH (63 [47–82] versus 43 [35–63] Wood Units·kg; P=0.014).ConclusionsPatients with LVH attributable to severe aortic stenosis had lower hyperemic blood flow per gram of myocardium and higher minimal myocardial resistance compared with patients without LVH.

Control of coronary vascular resistance by eicosanoids via a novel GPCR.

Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We applied a chemoproteomics strategy using a clickable photoaffinity probe to identify G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor selective for two endogenous eicosanoids, 15-HETE and 14,15-EET, which act on the receptor to oppose each other's activity. The former increases mVSMC intracellular calcium via GPR39 and augments coronary microvascular resistance, and the latter inhibits these actions. Furthermore, we find that the efficacy of both ligands is potentiated by zinc acting as an allosteric modulator. Measurements of coronary perfusion pressure (CPP) in GPR39-null hearts using the Langendorff preparation indicate the receptor senses these eicosanoids to regulate microvascular tone. These results implicate GPR39 as an eicosanoid receptor and key regulator of myocardial tissue perfusion. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.

Refining Our Understanding of the Flow Through Coronary Artery Branches; Revisiting Murray's Law in Human Epicardial Coronary Arteries.

Background: Quantification of coronary blood flow is used to evaluate coronary artery disease, but our understanding of flow through branched systems is poor. Murray’s law defines coronary morphometric scaling, the relationship between flow (Q) and vessel diameter (D) and is the basis for minimum lumen area targets when intervening on bifurcation lesions. Murray’s original law (Q α DP) dictates that the exponent (P) is 3.0, whilst constant blood velocity throughout the system would suggest an exponent of 2.0. In human coronary arteries, the value of Murray’s exponent remains unknown. Aim: To establish the exponent in Murray’s power law relationship that best reproduces coronary blood flows (Q) and microvascular resistances (Rmicro) in a bifurcating coronary tree. Methods and Results: We screened 48 cases, and were able to evaluate inlet Q and Rmicro in 27 branched coronary arteries, taken from 20 patients, using a novel computational fluid dynamics (CFD) model which reconstructs 3D coronary anatomy from angiography and uses pressure-wire measurements to compute Q and Rmicro distribution in the main- and side-branches. Outputs were validated against invasive measurements using a Rayflow™ catheter. A Murray’s power law exponent of 2.15 produced the strongest correlation and closest agreement with inlet Q (zero bias, r = 0.47, p = 0.006) and an exponent of 2.38 produced the strongest correlation and closest agreement with Rmicro (zero bias, r = 0.66, p = 0.0001). Conclusions: The optimal power law exponents for Q and Rmicro were not 3.0, as dictated by Murray’s Law, but 2.15 and 2.38 respectively. These data will be useful in assessing patient-specific coronary physiology and tailoring revascularisation decisions.

СТЕНОКАРДИЯ БЕЗ ОБСТРУКТИВНОГО ПОРАЖЕНИЯ КОРОНАРНЫХ АРТЕРИЙ (Часть 2). МЕТОДЫ ДИАГНОСТИКИ В КЛИНИЧЕСКОЙ ПРАКТИКЕ

Coronary vasomotor disorders are a common cause of angina pectoris without obstructive lesion of the coronary arteries (CA). Over the past decade, various non-invasive and invasive diagnostic methods have made it possible to comprehensively assess coronary vasomotor function and determine the endotypes of epicardial and microvascular dysfunction, which is important for stratification of cardiovascular risk and individualization of patient treatment. The basis for the diagnosis of the complex interaction of vasodilation and vasoconstriction of various parts of the coronary bed is a comprehensive intracoronary functional testing, which is recommended if the angina symptoms are persisting against the background of angiographically unchanged or moderately stenosed, blood flow non-limiting coronary arteries. The established parameters characterizing adequate vasodilation are coronary blood flow reserve and microvascular resistance. Increased vasoconstriction potential is diagnosed by intracoronary provocation test with acetylcholine, which allows verification of epicardial and/or microvascular vasospasm. The article discusses standardized criteria, non-invasive imaging methods and modern invasive examination algorithms used in the diagnosis of microvascular and vasospastic angina.

The Role of Coronary Microvascular Disease in Cardiomyophaties

Coronary microvascular disease (CMD) makes reference to the anatomically and functionally disorders affecting vascular compartments (&lt;400 mm diameter), covering a broad range of clinical conditions in which the structure and function of the coronary microcirculation is affected. CMD is characterized by an impaired coronary flow reserve (cut-off values of 2.0-2.5) or an abnormally index of coronary microvascular resistance (IMR &gt;25) and/or focal or diffuse vasoconstriction during acetylcholine challenge, with an important role in myocardial perfusion. The aim of this work is to review CMD, definition, clinical manifestations, diagnosis method (non invasive and invasive approach) and the role of CMD in the main cardiomiophaties, such as Hypertrophic cardiomiopathy, none idiomatic dilated cardiomiopathy and infiltrative miocardiophaty.

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.

Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis.

Background: Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis.Methods: Fourteen pigs were randomized to sham (n = 7) or fecal peritonitis-induced sepsis (n = 7) procedures. At baseline, 6 and 12 h after peritonitis induction, the animals underwent general and coronary hemodynamic evaluation, including determination of autoregulatory breakpoint pressure and adenosine-induced maximal coronary vasodilation for coronary flow reserve and hyperemic microvascular resistance calculation. Endothelial-derived vasodilatory response was assessed both in vivo and ex vivo using bradykinin. Coronary arteries were sampled for pathobiological evaluation.Results: Sepsis resulted in a right shift of the autoregulatory breakpoint pressure, decreased coronary blood flow reserve and increased hyperemic microvascular resistance from the 6th h after peritonitis induction. In vivo and ex vivo endothelial vasomotor function was preserved. Sepsis increased coronary arteries expressions of nitric oxide synthases, prostaglandin I2 receptor, and prostaglandin F2α receptor.Conclusion: Autoregulation and metabolic blood flow regulation were both impaired in the coronary circulation during experimental hyperdynamic sepsis, although endothelial vasodilatory response was preserved.

Endothelium in Coronary Macrovascular and Microvascular Diseases.

:The endothelium plays a pivotal role in the regulation of vascular tone by synthesizing and liberating endothelium-derived relaxing factors inclusive of vasodilator prostaglandins (eg, prostacyclin), nitric oxide (NO), and endothelium-dependent hyperpolarization factors in a distinct blood vessel size–dependent manner. Large conduit arteries are predominantly regulated by NO and small resistance arteries by endothelium-dependent hyperpolarization factors. Accumulating evidence over the past few decades has demonstrated that endothelial dysfunction and coronary vasomotion abnormalities play crucial roles in the pathogenesis of various cardiovascular diseases. Structural and functional alterations of the coronary microvasculature have been coined as coronary microvascular dysfunction (CMD), which is highly prevalent and associated with adverse clinical outcomes in many clinical settings. The major mechanisms of coronary vasomotion abnormalities include enhanced coronary vasoconstrictive reactivity at epicardial and microvascular levels, impaired endothelium-dependent and endothelium-independent coronary vasodilator capacities, and elevated coronary microvascular resistance caused by structural factors. Recent experimental and clinical research has highlighted CMD as the systemic small artery disease beyond the heart, emerging modulators of vascular functions, novel insights into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will summarize the current knowledge on the endothelial modulation of vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases from bench to bedside, with a special emphasis placed on the mechanisms and clinical implications of CMD.

Microvascular Dysfunction in Patients With Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve.

Background: 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 hyperemic 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 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 = 2.38 ± 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 < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 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 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.

Utilising clinical data to personlaise boundary conditions significantly improves the accuracy of angiography based virtual FFR

Abstract Background Angiography-derived computed (virtual) fractional flow reserve (vFFR) permits the assessment of coronary physiology without the need for a pressure wire or hyperaemia. However, accuracy is limited by assumptions made about coronary microvascular resistance (CMVR) [1]. We hypothesised that machine learning may allow us to “tune” our estimate of the CMVR to increase the accuracy of vFFR. Purpose To determine whether routine clinical data can personalise CMVR and improve the accuracy of vFFR on an individual case basis. Methods Patients with chronic coronary syndromes underwent coronary angiography with FFR assessment. Vessel-specific CMVR was computed using a 3D- computational fluid dynamics simulation with invasively measured proximal and distal pressures. Predictive models were created using non-linear autoregressing moving average with exogenous inputs (NARMAX) modelling with computed CMVR as the dependent variable. vFFR was computed using previously described methods [2]. Three simulations were run, using: 1) a generic CMVR value (Model A); 2) a NARMAX-predicted CMVR based upon a panel of simple clinical data (Model B); and 3) a NARMAX-predicted CMVR incorporating echocardiographic data (Model C). The diagnostic and quantitative accuracy of each model was compared with directly measured FFR. Results Eighty four patients underwent coronary angiography with FFR assessment in 157 vessels. Mean age was 64 (±0.1) years and 64 (76%) were male. Mean FFR was 0.79 (±0.15). Mean CMVR was 1.01e+10 Pa/m3 s–1. vFFR error with Model A was ±0.10, with Model B was ±0.07 (p&amp;lt;0.001) and with Model C was ±0.05 (p&amp;lt;0.001) (Table 1). Conclusion vFFR is dependent upon not only the epicardial stenosis, but also the CMVR, estimation of which can be personalised based upon clinical and echocardiographic data. This can be used to increase the accuracy of vFFR. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): British Heart Foundation Clinial Research Training FellowshipNIHR i4i grant Table 1

Thermodilution-derived volumetric resting coronary blood flow measurement in humans.

Quantification of microvascular function requires the measurement of flow and resistance at rest and during hyperaemia. Continuous intracoronary thermodilution accurately measures coronary flow during hyperaemia. The aim of this study was to investigate whether continuous coronary thermodilution using lower infusion rates also enables volumetric coronary blood flow measurements (in mL/min) at rest. In 59 patients (88 arteries), the ratio of distal to proximal coronary pressure (Pd/Pa), as well as absolute blood flow (in mL/min) by continuous thermodilution, was recorded using a pressure/temperature guidewire. Saline was infused at rates of 10 and 20 mL/min. In 27 arteries, Doppler average peak velocity (APV) was measured simultaneously. Pd/Pa, APV, thermodilution-derived coronary flow reserve (CFRthermo) and coronary flow velocity reserve (CFVR) were assessed. In 10 arteries, simultaneous recordings were obtained at saline infusion rates of 6, 8, 10 and 20 mL/min. Compared to baseline, saline infusion at 10 mL/min did not change Pd/Pa (0.95±0.05 versus 0.94±0.05, p=0.49) or APV (22±8 versus 23±8 cm/s, p=0.60); conversely, an infusion rate of 20 mL/min induced a decrease in Pd/Pa and an increase in APV. Stable thermodilution tracings were obtained during saline infusion at 8 and 10 mL/min, but not at 6 mL/min. Mean values of CFRthermo and CFVR were similar (2.78±0.91 versus 2.76±1.06, p=0.935) and their individual values correlated closely (r=0.89, 95% CI: 0.78-0.95, p<0.001). In addition to hyperaemic flow, continuous thermodilution can quantify absolute resting coronary blood flow; therefore, it can be used to calculate coronary flow reserve and microvascular resistance reserve.

Normal values of thermodilution-derived absolute coronary blood flow and microvascular resistance in humans.

Absolute hyperaemic coronary blood flow (Q, in mL/min) and resistance (R, in Wood units [WU]) can be measured invasively by continuous thermodilution. The aim of this study was to assess normal reference values of Q and R. In 177 arteries (69 patients: 25 controls, i.e., without identifiable coronary atherosclerosis; 44 patients with mild, non-obstructive atherosclerosis), thermodilution-derived hyperaemic Q and total, epicardial, and microvascular absolute resistances (Rtot, Repi, and Rmicro) were measured. In 20 controls and 29 patients, measurements were obtained in all three major coronary arteries, thus allowing calculations of Q and R for the whole heart. In 15 controls (41 vessels) and 25 patients (71 vessels), vessel-specific myocardial mass was derived from coronary computed tomography angiography. Whole heart hyperaemic Q tended to be higher in controls compared to patients (668±185 vs 582±138 mL/min, p=0.068). In the left anterior descending coronary artery (LAD), hyperaemic Q was significantly higher (293±102 mL/min versus 228±71 mL/min, p=0.004) in controls than in patients. This was driven mainly by a difference in Repi (43±23 vs 83±41 WU, p=0.048), without significant differences in Rmicro. After adjustment for vessel-specific myocardial mass, hyperaemic Q was similar in the three vascular territories (5.9±1.9, 4.9±1.7, and 5.3±2.1 mL/min/g, p=0.44, in the LAD, left circumflex and right coronary artery, respectively). The present report provides reference values of absolute coronary hyperaemic Q and R. Q was homogeneously distributed in the three major myocardial territories but the large ranges of observed hyperaemic values of flow and of microvascular resistance preclude their clinical use for inter-patient comparison.