Impaired Coronary Flow Reserve Research Articles

Risk factors for unsuccessful restoration of coronary flow reserve after coronary bypass surgery

Objectives: Coronary flow reserve (CFR) is a strong predictor of cardiovascular events and prognosis in patients with coronary artery disease. This study aimed to evaluate preoperative factors associated with the unsuccessful restoration of CFR after coronary artery bypass grafting (CABG). Methods: Included in this study were the 65 patients who presented with functionally significant left anterior descending artery (LAD) lesions confirmed by both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), and who underwent successful CABG at our hospital within the study period. After CABG, graft patency was confirmed by coronary computed tomography angiography, and CFR in the LAD artery was measured by echocardiography. We defined postoperative CFR <2.5 as impaired CFR, and CFR ≥2.5 as preserved CFR. Results: Of the 65 patients, 14 patients (22%) showed impaired CFR, while 51 patients had preserved CFR. Patients with impaired CFR had significantly higher HbA1c (6.7% vs. 6.0%, P < 0.01), greater use of insulin (43% vs. 4%, P < 0.01), longer lesion length (33 mm vs. 25 mm, P = 0.044), and lower iFR (0.69 vs 0.81, P = 0.01) than those with preserved CFR, although both groups had comparable FFR (0.65 vs 0.64, P = 0.46). In receiver operating characteristic curve analysis, iFR had a significantly larger area under the curve than FFR in terms of the prediction of impaired CFR (0.74 vs 0.42, P = 0.01). Conclusions: Poorly-controlled preoperative diabetes, greater reliance on insulin, longer lesion length and lower iFR were associated with postoperative impaired CFR, suggesting the involvement of microvascular dysfunction.

Prognostic Implications of Resistive Reserve Ratio in Patients With Nonobstructive Coronary Artery Disease With Myocardial Bridging.

Myocardial bridging (MB) is accompanied by the dynamic extravascular compression of epicardial coronary arteries, leading to intracoronary hemodynamic disturbance with abnormal coronary flow profiles. We aimed to evaluate the prognostic implications of resistive reserve ratio (RRR), a composite measure of flow and pressure parameters that represents the vasodilatory capacity of the coronary arteries, in patients with angina with nonobstructive coronary artery disease (ANOCA) and MB, in comparison with coronary flow reserve (CFR). In this retrospective cohort study, we included patients with ANOCA who underwent coronary reactivity testing, where MB was identified by transient constriction in coronary artery segments between systole and diastole. Abnormal CFR and RRR were defined as <2.5 and <2.62, respectively. Major adverse cardiac events, including cardiovascular death, stroke, myocardial infarction, heart failure, and late revascularization, served as outcomes. Among 1251 patients with ANOCA, 191 (15.3%) had MB. The prevalence of abnormal CFR or RRR was not significantly different between patients with and without MB (P=0.144 and P=0.398, respectively). Over a median follow-up time of 6.9 years, abnormal RRR predicted major adverse cardiac events in patients with MB (hazard ratio [HR], 4.38 [95% CI, 1.71-11.21]; P=0.002) and without MB (HR, 1.91 [95% CI, 1.38-2.64]; P<0.001). Abnormal CFR predicted major adverse cardiac events in patients without MB (HR, 2.15 [95% CI, 1.54-3.00]; P<0.001), whereas it was not predictive of major adverse cardiac events in patients with MB (HR, 2.29 [95% CI, 0.93-5.65]; P=0.073). In patients with ANOCA and MB, impaired RRR was superior to impaired CFR in distinguishing patients at a higher risk of future adverse events, suggesting that RRR may serve as a risk stratification tool in patients with MB and ANOCA.

Novel diagnostic approaches and management of coronary microvascular dysfunction

The mechanism underlying ischaemic heart disease (IHD) has been primarily attributed to obstructive coronary artery disease (CAD). However, non-obstructive coronary arteries are identified in >50% of patients undergoing elective coronary angiography, recently leading to growing interest in the investigation and management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA). INOCA is an umbrella term encompassing a multiple spectrum of possible pathogenetic entities, including coronary vasomotor disorders which consist of two major endotypes: coronary microvascular dysfunction (CMD) and vasospastic angina. Both conditions can coexist and be associated with concomitant obstructive CAD. Particularly, CMD refers to myocardial ischaemia due to reduced vasodilatory capacity of coronary microcirculation secondary to structural remodelling or impaired resting microvascular tone (functional) or a combination of both. CMD is not a benign condition and is more prevalent in women presenting with chronic coronary syndrome compared to men. In this setting, an impaired coronary flow reserve has been associated with increased risk of major adverse cardiovascular events. ANOCA/INOCA patients also experience impaired quality of life and associated increased healthcare costs. Therefore, research in this scenario has led to better definition, classification, and prognostic stratification based on the underlying pathophysiological mechanisms. The development and validation of non-invasive imaging modalities, invasive coronary vasomotor function testing and angiography-derived indices provide a comprehensive characterisation of CMD. The present narrative review aims to summarise current data relating to the diagnostic approach to CMD and provides details on the sequence that therapeutic management should follow.

SEX DIFFERENCES IN THE CORONARY SYSTEM OF THE HUMAN HEART

The aim of this study is to investigate sex differences in the coronary system of the heart, considering all relevant consequence, and to compile and analyze the gathered data. Materials and Methods. The authors independently conducted a literature search and selection process using the PubMed database for the review, followed by the generalization of the obtained data. Results. Women exhibit a higher propensity than men for certain cardiovascular diseases, including persistent angina, non-obstructive coronary heart disease, coronary microvascular dysfunction, spontaneous coronary artery dissection, stress cardiomyopathy, and heart failure with preserved ejection fraction (HFpEF). In comparison to men, women typically present with elevated rates of underlying comorbidities, encompassing not only advanced age but also hypertension, diabetes mellitus, obesity, chronic renal failure, peripheral vascular disease, HFpEF, and inflammatory conditions like rheumatoid arthritis. Many of these conditions are linked to diffuse atherosclerosis and microvascular ischemia, with notable parallels between non-obstructive coronary heart disease and coronary microvascular dysfunction. Special attention is paid to patients sharing an increased risk of coronary heart disease events, which is consistent between women and men, except for those with severe coronary flow reserve (CFR) impairment, where women demonstrate an even higher risk. In particular, in cases where CFR impairment is not attributable to obstructive coronary heart disease (precluding revascularization to mitigate cardiovascular risk), there may be justification for a novel therapeutic approach for systemic coronary heart disease management. Cases of severe coronary microvascular dysfunction, often concurrent with non-obstructive coronary heart disease, may indicate a shared mechanism influencing coronary heart disease risk in both genders. This mechanism might involve inflammation, endothelial dysfunction, and heightened cardiomyocyte oxygen demand, culminating in microvascular ischemia, myocardial injury, and compromised cardiac function. Conclusions. Enhanced comprehension of the interplay between coronary vasomotor dysfunction and the concomitance of coronary heart disease with other conditions, such as insulin resistance and heart failure, could foster the advancement of novel systemic treatments aimed at leveraging “complete revascularization” more effectively.

CORRELATION BETWEEN RETINAL MICROCIRCULATION, ECHOCARDIOGRAPHIC PARAMETERS AND MYOCARDIAL CORONARY FLOW RESERVE

Objective: Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated the possible relationship between retinal microcirculation, positron emission tomography myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi) Design and method: Nineteen hypertensive patients (mean age 65 ± 11, 10 F) without flow-limiting epicardial coronary artery disease underwent patients wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera, echocardiography, including MEEi computation, and cardiac 13NH3 positron emission tomography (13NH3 PET) with assessment of myocardial coronary flow reserve (CFR). A positive 13NH3 PET was defined as a ratio of stress (regadenoson) myocardial blood flow (MBF)/mass and resting MBF/mass lower than 2. Results: No significant differences of demographic parameters were observed between patients with positive (n=6) vs negative (n=13) 13NH3 PET. In all patients WLR was significantly related to BMI (0,50, p=0.02), age (r=0.49, p=0.03)and LVMi (r=0.48, p=0.03) at univariate analysis. A negative correlation was also observed between WLR and total CFR (-0.64, p=0.003) and MMEi (-0.35, p=0.13). The relationship between WLR and CFR remained significant after adjustment for age and BMI (r=-0.49, p=0.047). Conclusions: In hypertensive patients without flow-limiting epicardial coronary artery disease, retinal WLR could reflect the presence of structural alterations in coronary microcirculation, possibly contributing to an impairment of CFR and to early LV dysfunction, as detected by low values of MEEi.

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.

Angina and no obstruction on coronary angiography : New approaches to the diagnosis and treatment of vasomotor disorders

Clinical management of patients with angina and no obstructive coronary artery disease (ANOCA) is still challenging. This scenario affects up to 50% of patients undergoing diagnostic coronary angiography due to suspected coronary artery disease. Many patients report along and debilitating history before adequate diagnostics and management are initiated. This article describes the current recommendations for diagnostic assessments and treatment in patients with ANOCA. Focus is placed on invasive diagnostics in the catheter laboratory, pharmacological/interventional treatment as well as the patient journey. In patients with ANOCA, the current European Society of Cardiology (ESC) guidelines suggest that invasive assessments using acetylcholine and adenosine for the diagnosis of an underlying coronary vasomotor disorder should be considered. Acetylcholine is used to diagnose coronary spasm, whereas adenosine is used in conjunction with awire-based assessment for the measurement of coronary flow reserve and microvascular resistance. The invasive assessments allow the determination of what are referred to as endotypes (coronary spasm, impaired coronary flow reserve, enhanced microvascular resistance or acombination thereof). Establishing adiagnosis is helpful to: (a)initiate targeted treatment to improve quality of life, (b)reassure the patient that acardiac cause is found and (c)to assess individual prognosis. Currently, patients with ANOCA are often not adequately managed. Referral to specialised centres is recommended to prevent long and debilitating patient histories until expertise in diagnosis and treatment becomes more widespread.

Implementation of Microcirculation Examination in Clinical Practice-Insights from the Nationwide POL-MKW Registry.

Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients' clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often.

Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia

Background and aimsMicrovascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH). MethodsFour groups of asymptomatic individuals aged 30–59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry. ResultsThe groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups. ConclusionsCoronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.

Coronary flow reserve predicts response to anti-ischaemic therapy in patients with angina with non-obstructive coronary arteries

Abstract Background Half of all patients with angina have non-obstructive coronary arteries (ANOCA) and therapy is often empirical. The CorMicA trial showed improved symptom scores with a physiology-guided approach but the mechanistic relationship between physiological classification and outcome remains unclear. Purpose To assess if invasively assessed coronary flow reserve (CFR) can predict change in exercise time (ET) and angina-specific quality of life (QOL) in response to anti-ischaemic therapy in patients with ANOCA. Methods Prospective, randomised, crossover trial of consecutively evaluated patients with ANOCA. Inclusion criteria: (i) typical and limiting angina; (ii) non-obstructive coronary arteries (fractional flow reserve &amp;gt;0.80); (iii) normal left ventricular systolic function. Coronary physiological assessment was performed using a pressure and Doppler dual sensor-tipped wire in the left anterior descending artery and microvascular dysfunction defined a priori as CFR&amp;lt;2.5 in response to intravenous Adenosine. Patients, clinicians, and researchers were blinded to coronary physiology data. All patients were then sequentially treated with Amlodipine and Ranolazine (in a randomised order), in 4 week blocks with 1 week washout (Figure 1). The outcome measures are 1) Primary (objective): change in ET on exercise stress testing and 2) Secondary (subjective): change in angina-specific QOL on Seattle Angina Questionnaire (SAQ). Data are presented as mean±SD or median (IQR). Results Sixty-six patients with ANOCA were enrolled into the study [62±8 years, 64% females, CCS 3 (2, 3)]; eight patients were excluded. Forty patients had an impaired CFR (2.0±0.3), whilst 18 patients had normal CFR (3.1±0.6), with similar baseline ET (324±133 vs 321±136 seconds, respectively; p=0.94). Patients with an impaired CFR improved their exercise capacity with Ranolazine (ΔET 70±108 seconds; p&amp;lt;0.01) and Amlodipine (ΔET 70±82 seconds; p&amp;lt;0.01). However, there was no such improvement in patients with normal CFR, with either Ranolazine (ΔET 16±88 seconds; p=0.49) or Amlodipine (ΔET 21±59 seconds; p=0.18) (Figure 2). There was no evidence of a training effect (ΔET between visit 1 and visit 4 was 15±112 seconds; p=0.57). Angina-specific QOL improved in patients with impaired CFR [Ranolazine ΔSAQ 12±18 (p&amp;lt;0.01) and Amlodipine ΔSAQ 8±13 (p&amp;lt;0.01)]; the change in SAQ was less marked in patients with normal CFR [Ranolazine ΔSAQ 7±14 (p=0.07) and Amlodipine ΔSAQ 6±10 (p=0.03)]. Conclusion Patients with impaired CFR demonstrated an improved exercise capacity, whereas patients with normal CFR did not. CFR-guided management of ANOCA is likely to be superior to an empirical strategy. This type of physiology-blinded study design could act as a template for future therapy trials in patients with stable angina.Study design for therapeutic trialResponse to anti-ischaemic therapy

Association of microvascular dysfunction with cardiovascular outcomes in heart failure with preserved ejection fraction

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a disease that portends an increased risk of morbidity and mortality. Studies have reported an association between HFpEF and microvascular dysfunction, however this association and its prognostic significance remain unclear. The purpose of this meta-analysis is to evaluated the association of microvascular dysfunction with cardiovascular outcomes in patients with HFpEF. Methods A literature search was conducted for studies evaluating the association between microvascular dysfunction measured with global myocardial flow reserve (GMFR) and coronary flow reserve (CFR) and major adverse cardiovascular events (MACE) in patients with HFpEF. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum follow up duration was one year. Results A total of 5 studies with 448 patients (252 with HFpEF, 196 healthy controls) met inclusion criteria for evaluation of the association of GMPR with HFpEF. Patients with HFpEF had a significantly lower GMPR compared to healthy controls (SMD -0.83, 95% CI -1.03,-0.63; p&amp;lt;0.01). Heterogeneity was moderate: Chi2=9.5, df=4, I2 = 58%. Only 2 studies were identified that reported on the evaluation of CFR in patients with HFpEF so meta-analysis could not be reliably performed. A total of 4 studies with 591 HFpEF patients (284 with reduced CFR and 307 with normal CFR) met inclusion for evaluating the association with MACE. Mean follow-up was 36 months. Patients with impaired CFR &amp;lt;2.0 had significantly higher risk of MACE compared to patients with normal CFR (OR 8.89, 95% CI 3.77-20.92; P&amp;lt;0.01). Heterogeneity was low: Chi2=4.77, df=3, I2=37%. Conclusion Patients with HFpEF have significant microvascular disease compared to patients without HFpEF, which is associated with an increased risk of MACE. Additional high-quality studies are required to further elucidate this association and determine the utility of targeted medical therapy.

Myocardial microvascular dysfunction in asymptomatic patients with hereditary dyslipidemia

Abstract Introduction Microvascular dysfunction underlies the pathophysiology of many cardiovascular disease (CVD) conditions and is strongly associated with future cardiovascular events. Hereditary forms of dyslipidaemia such as familial hypercholesterolemia (FH) and high levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerotic CVD but the degree of microvascular dysfunction in asymptomatic individuals is not fully explored. Purpose To evaluate the presence of microvascular dysfunction in asymptomatic individuals with the hereditary dyslipidaemias FH and high Lp(a). Methods Asymptomatic individuals without manifest CVD were recruited to four groups with 30 subjects in each; 1) controls with Lp(a)&amp;lt;30 nmol/L, 2) FH+Lp(a)&amp;lt;30 nmol/L, 3) FH+Lp(a)&amp;gt;125 nmol/L, and 4) isolated Lp(a)&amp;gt;125 nmol/L without FH. FH diagnoses were confirmed by genetic analysis. Transthoracic doppler echocardiography was used to record coronary flow in the distal part of the left anterior descending artery at rest and during hyperaemia induced by intravenous infusion of adenosine. Coronary flow reserve (CFR) was calculated by dividing hyperaemic to basal flow. Peripheral microvascular endothelial function was determined by recording reactive hyperaemia index (RHI) by peripheral arterial tonometry in the index fingers of both hands. CFR and RHI were considered impaired if values were &amp;lt;2.5 and &amp;lt;1.67, respectively. Results The four groups were balanced in age (mean 42.6±8.4 years), sex (50% females), BMI (mean 25.0±4.7 kg/m2), and smoking status (5.0% current smokers). Low-density lipoprotein cholesterol was also similar across the four groups (mean 2.8±1.1 mmol/L) with the two FH groups being on cholesterol lowering treatment while the other two were pharmacologically naïve. The three groups with hereditary dyslipidaemia had a higher proportion of subjects with impaired CFR, 30.0% in each group compared to 6.6% in controls (p=0.014) (Figure 1A). The FH+Lp(a)&amp;lt;30 nmol/L and FH+Lp(a)&amp;gt;125 nmol/L groups had received cholesterol lowering treatment for a median (inter quartile range, IQR) of 4.0 (8.0) and 11.0 (11.0) years respectively (p&amp;lt;0.001). In the FH+Lp(a)&amp;gt;125 nmol/L group individuals with normal CFR had received significantly longer treatment (p=0.006) but not in the FH+Lp(a)&amp;lt;30 nmol/L group (p=0.568) (Figure 1B). There were no major differences in median CFR (p=0.550) (Figure 2A) or median RHI (p=0.341) (Figure 2B) levels between the four groups. Conclusion Asymptomatic individuals with the hereditary dyslipidaemias FH and/or high Lp(a) have a higher degree of coronary microvascular dysfunction compared to healthy controls. For individuals with combined traits FH and high Lp(a), the total treatment years of cholesterol lowering is associated with preserved coronary microvascular function suggesting CFR as a potential useful non-invasive tool for cardiovascular risk-stratification in patients with hereditary dyslipidaemias.Figure 1Figure 2

Abstract 18949: Bariatric Surgery is Associated With Improved Coronary Microvascular Function and Cardiorespiratory Fitness in Patients With Ischemia and Non-Obstructive Coronary Arteries (INOCA)

Introduction - Severe obesity is associated with cardiometabolic disease and coronary microvascular dysfunction, as reflected by impaired coronary flow reserve (CFR). Bariatric surgery promotes sustained weight loss and lower incidence of diabetic microvascular complications, but its effect on the coronary microcirculation is unclear. In this ongoing pilot study, we aimed to investigate the impact of bariatric surgery on CFR, endothelial function, and cardiorespiratory fitness in patients with severe obesity and INOCA. Methods - Consecutive patients (N=19) with severe obesity (BMI≥35 kg/m 2 ), exertional dyspnea and planned bariatric surgery were enrolled. Patients underwent cardiac stress positron emission tomography (PET), peripheral arterial tonometry (PAT), echocardiogram and cardiopulmonary exercise testing (CPET) at baseline and after a median of 6.2 months post-surgery (N=9 completed to date). CFR was quantified as stress/rest myocardial blood flow (MBF) from PET. Reactive hyperemia index (RHI), a marker of endothelial function, was calculated as the ratio between PAT signal post and pre-occlusion in the corresponding arm. Results - Median age was 50 (Q1-Q3 42-54) years and 63% were female. At baseline, median BMI was 43 (40-54), LVEF was 0.62, and %LV visual ischemia was 0. Higher BMI inversely correlated with CFR (r= -0.53, p=0.02). As compared to baseline, patients post-surgery (78% sleeve gastrectomy, 22% gastric bypass) had significantly decreased BMI (45.2 vs. 34.3, p=0.008) and improved stress MBF [1.8 (1.3-2.2) vs. 2.4 (1.8-2.8), p&lt;0.02], CFR [2.3 (1.9-2.6) vs. 3.1 (2.4-3.6), p&lt;0.02] and peripheral endothelial function [RHI 1.5 (1.4-1.8) vs. 2.4 (1.8-2.8) vs. p=0.04]. These changes were accompanied on CPET by significantly higher exercise workload [112 (84.2-146) vs. 124.5 (90.5-149) W, p=0.046] and relative peak VO 2 [12.5 (11.9-14) vs. 15.2 (12.6-17) mL/kg/min, p=0.028]. Higher stress MBF directly correlated with relative peak VO 2 (r=0.53, p=0.04). Conclusion - In this pilot clinical study, bariatric surgery was associated with significant improvements in coronary microvascular function, peripheral endothelial function, and cardiorespiratory fitness in symptomatic patients with severe obesity after six months.

Abstract 197: Establishing a Novel Pulse Wave Velocity-Guided Mouse Model of Cardiac Arrest With Different Durations

Background: Neurological and cardiovascular injuries are the leading causes of death following cardiac arrest (CA). Few rodent models recapitulate these post-resuscitation symptoms. Aims: To develop extended ischemic CA models under Pulse Wave Velocity ( PWV) guidance with consistent post-CA brain injury (PCABI) and coronary dysfunction as potential therapeutic targets and mechanical studies. Methods: Forty-eight mice were randomized into four experimental groups (control, 8-, 12-, and 16-min CA). Potassium chloride (KCL) was intravenously injected, resulting in immediate asystole. Mice were resuscitated with an injection of epinephrine and manual chest compressions. PWV was monitored for the left carotid artery velocity and coronary flow reserve (CFR). Resuscitability, synaptic density in the hippocampal CA1 region, blood-brain barrier (BBB), and neurologic deficit scores (NDS) were also evaluated. Results: The PWV could monitor rapid asystole after KCL injection, improve cardiopulmonary resuscitation (CPR) success rates, and avoid the pre-matured end of resuscitation. Compared to the standard control, mice with 8-min CA had preserved CFR, mild loss of synaptic density (p&gt;0.05), mild hypothermal, and a normal electrocardiogram. They maintained BBB integrity with no significant change to neurologic function. Compared with a 92% CPR success rate in 8 min-CA mice, 12 min-CA mice had 83%, and 16 min-CA mice had 58% resuscitability. Twelve min-CA mice had significantly impaired CFR at 24 hours and high lethality (40%, P&lt;0.05) within the first three days; 16 min-CA mice worsened (33% survival rate, p&lt;0.01). The 24 hrs electron microscope showed that CA-induced synaptic vesicle densities were ischemic time-dependent [350±60 (control) vs. 289±64 (8 min CA) vs. 269±34 (12 min CA) vs. 181±41/field (16 min CA)], consistent with NDS. The cerebrum and hippocampus were the most valuable regions, indicated by Evans blue evaluation at 48 hrs after CA. Conclusions: We established elongated PWV-guided CA models as with successful CPR, post-CA neurological deficits, leaky BBB, loss of synaptic density, coronary endothelial dysfunction, and even death in mice, which closely recapitulated the post-resuscitation symptoms in survived patients after CPR.

Triple Vessel Coronary Artery Disease Needs a Consistent Definition for Management Guidelines

For over forty years, coronary artery bypass grafting (CABG) has been recommended to patients with triple vessel disease (TVD) with the aim of providing a survival benefit compared to medical therapy. Generally, the survival benefit of CABG is determined by (a) the volume of myocardium at risk of infarction according to the extent of coronary artery disease (CAD), (b) the impairment of coronary flow reserve according to severity of coronary stenoses, severity of symptoms, or objective evidence of regional ischemia, and (c) the impairment of myocardial reserve according to left ventricular function and viability. The most frequently used index of survival benefit is the extent of CAD as described by the terms of the left main coronary stenosis and TVD. However, TVD has been inconsistently defined in randomised controlled trials. Furthermore, international guidelines do not provide a specific definition of TVD. This impacts a substantially sized and high-risk population. Here, we argue that the definition of TVD should include diseases in the major artery in each of the three coronary territories in order to estimate the survival benefit provided by CABG.

Accelerated stenotic flow in the left anterior descending coronary artery explains the causes of impaired coronary flow reserve: an integrated transthoracic enhanced Doppler study.

Accelerated stenotic flow (AsF) in the entire left anterior descending coronary artery (LAD), assessed by transthoracic enhanced color Doppler (E-Doppler TTE), can reveal coronary stenosis (CS) and its severity, enabling a distinction between the microcirculatory and epicardial causes of coronary flow reserve (CFR) impairment. Eighty-four consecutive patients with a CFR <2.0 (1.5 ± 0.4), as assessed by E-Doppler TTE, scheduled for coronary angiography (CA) and eventually intracoronary ultrasounds (IVUS), were studied. CFR was calculated by the ratio of peak diastolic flow velocities: during i.v. adenosine (140 mcg/Kg/m) over resting; AsF was calculated as the percentage increase of localized maximal velocity in relation to a reference velocity. CA showed ≥50% lumen diameter narrowing of the LAD (critical CS) in 68% of patients (57/84) vs. non-critical CS in 32% (27/84). Based on the established CA/IVUS criteria, the non-critical CS subgroup was further subdivided into 2 groups: subcritical/diffuse [16/27 pts (57%)] and no atherosclerosis [11/27 pts (43%)]. CFR was similar in the three groups: 1.4 ± 0.3 in critical CS, 1.5 ± 0.4 in subcritical/diffuse CS, and 1.6 ± 0.4 in no atherosclerosis (p = ns). Overall, at least one segment of accelerated stenotic flow in the LAD was found in 73 patients (87%), while in 11 (13%) it was not. The AsF was very predictive of coronary segmental narrowing in both angio subgroups of atherosclerosis but as expected with the usage of different cutoffs. On the basis of the ROC curve, the optimal cutoff was 109% and 16% AsF % increment to successfully distinguish critical from non-critical CS (area under the curve [AUC] = 0.99, p < 0.001) and diffuse/subcritical from no CS (AUC = 0.91%, p < 0.001). Sensitivity and specificity were 96% and 100% and 82% and 100%, respectively. E-Doppler TTE is highly feasible and reliable in detecting the CS of any grade of severity, distinguishing epicardial athero from microvascular causes of a severe CFR reduction.

Particularities of coronary physiology in patients with atrial fibrillation: insights from combined pressure and flow indices measurements.

Symptoms suggestive of myocardial ischemia are frequently encountered in patients with atrial fibrillation (AF) even in the absence of obstructive coronary artery disease. Nevertheless, an in-depth characterisation of coronary physiology in patients with AF is currently lacking. We aim to provide an insight into the characteristics of coronary physiology in AF, by performing simultaneous invasive measurements of coronary flow- and pressure- indices in a real-life population of patients with AF and indication of coronary angiography. This is a prospective open label study including patients with permanent or persistent AF and indication of coronary angiography showing intermediate coronary stenosis requiring routine physiological assessment (n = 18 vessels from 14 patients). We measured FFR (fractional flow reserve), and Doppler-derived coronary flow indices, including CFR (coronary flow reserve) and HMR (hyperaemic microvascular resistance). From the analysed vessels, 18/18 vessels (100%) presented a pathological CFR (<2.5), indicative of coronary microvascular dysfunction (CMD), and 3/18 (17%) demonstrated obstructive epicardial coronary disease (FFR ≤ 0.8). A large proportion of vessels (15/18; 83%) showed discordant FFR/CFR with preserved FFR and low CFR. 47% of the coronary arteries in patients with AF and non-obstructive epicardial coronary disease presented structural CMD (HMR ≥ 2.5 mmHg/cm/s), and were associated with high BMR and an impaired response to adenosine. Conversely, vessels from patients with AF and non-obstructive epicardial coronary disease with functional CMD (HMR < 2.5 mmHg/cm/s) showed higher bAPV. The permanent AF subpopulation presented increased values of HMR and BMR compared to persistent AF, while structural CMD was more often associated with persistent symptoms at 3 months, taking into account the limited sample size of our study. Our findings highlight a systematically impaired CFR in patients with AF even in the absence of obstructive epicardial coronary disease, indicative of CMD. In addition, patients with AF presented more prevalent structural CMD (HMR ≥ 2.5 mmHg/cm/s), characterized by reduced hyperaemic responses to adenosine, possibly interfering with the FFR assessment.

Regional CZT myocardial perfusion reserve for the detection of territories with simultaneously impaired CFR and IMR in patients without obstructive coronary artery disease: a pilot study

ObjectivesTo assess the diagnostic performances of CZT myocardial perfusion reserve (MPR) for the detection of territories with simultaneous impaired coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients without obstructive coronary artery disease. MethodsPatients were prospectively included before being referred for coronary angiography. All patients underwent CZT MPR before invasive coronary angiography (ICA) and coronary physiology assessment. Rest and dipyridamole-induced stress myocardial blood flow (MBF) and MPR were quantified using 99mTc-SestaMIBI and a CZT camera. Fractional flow reserve (FFR), Thermodilution CFR, and IMR were assessed during ICA. ResultsBetween December 2016 and July 2019, 36 patients were included. 25/36 patients presented no obstructive coronary artery disease. A complete functional assessment was performed in 32 arteries. No territory presented a significant ischemia on CZT myocardial perfusion imaging. A moderate yet significant correlation was observed between regional CZT MPR and CFR (r = 0.4, P = .03). Sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT MPR versus the composite invasive criterion (impaired CFR and IMR) were 87 [47% to 99%], 92% [73% to 99%], 78% [47% to 93%], 96% [78% to 99%], and 91% [75% to 98%], respectively. All territories with a regional CZT MPR ≤ 1.8 showed a CFR < 2. Regional CZT MPR values were significantly higher in arteries with CFR ≥ 2 and IMR < 25 (negative composite criterion, n = 14) than in those with CFR < 2 and IMR ≥ 25 (2.6 [2.1 to 3.6] versus 1.6 [1.2 to 1.8]), P < .01). ConclusionRegional CZT MPR presented excellent diagnostic performances for the detection of territories with simultaneously impaired CFR and IMR reflecting a very high cardiovascular risk in patients without obstructive coronary artery disease.

Impaired endothelial glycocalyx, vascular dysfunction and myocardial deformation four months after Covid-19 infection are partially improved at twelve months

Abstract Funding Acknowledgements Type of funding sources: None. Introduction COVID-19 patients present impaired subclinical markers of cardiovascular and endothelial function. Subclinical myocardial and vascular dysfunction during COVID-19 disease have been associated with worse outcomes and higher mortality risk. Purpose We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function at four and twelve months after the infection Methods We recruited 70 patients who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four and twelve months after a confirmed COVID-19 infection and 70 healthy individuals with similar clinical characteristics. At four and twelve months we measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) malondialdehyde (MDA), an oxidative stress marker. Results At four months, COVID-19 patients displayed higher values of PBR5–25 compared to control group (p&amp;lt;0.001) which increased at twelve months (p&amp;lt;0.001). FMD, PWV and cSBP values were similar between 4 and 12 months (p&amp;gt;0.05 for all the comparisons) and higher than those in controls (p&amp;lt;0.001, p = 0.057, p = 0.003 respectively). At four months, COVID-19 patients presented impaired CFR and LVGLS values which were improved at twelve months (p = 0.002, p = 0.069 respectively), though remained impaired compared to controls (p = 0.003 for all the comparisons). At four months, COVID-19 patients had impaired RVGLS values which were significantly improved at twelve months (p = 0.001) and showed no statistically significant difference compared to controls (p&amp;gt;0.05). COVID-19 patients at four months display higher myocardial wasted work and decreased myocardial efficiency compared to controls (p = 0.01, p = 0.006, respectively). There was a modest improvement in GWW and GWE at twelve months, (p = 0.043, p = 0.001, respectively); however, these markers remained impaired compared to controls (p&amp;gt;0.05). At four months, MDA was higher in COVID-19 patients compared to control group and significantly decreased at twelve months (p&amp;lt;0.001); however, these values remain higher than in controls (p = 0.002). Conclusions SARS-CoV-2 causes endothelial and cardiovascular dysfunction which are partially restored at twelve months after the infection.

CORONARY MICROVASCULAR DISEASE IS ASSOCIATED WITH ARTERIAL STIFNESS IN PATIENTS WITH ISCHEMIA AND NO OBSTRUCTIVE CORONARY ARTERIES

Objective: There is a gap in the literature regarding the association between stiffness and myocardial ischemia. Arterial stiffness (AS) is an independent risk factor for cardiovascular disease, directly related to coronary atherosclerosis, an entity with an unfavorable cardiovascular prognosis frequently encountered in patients with hypertension. The aim of this study was to investigate the relationship between AS and Coronary Microvascular Dysfunction (MVD). Design and method: We examined 23 hypertensive patients [10 female, 43%, mean age: 61.5±10.1 years, mean office blood pressure (BP): 147/88±10/9 mmHg] and 28 MVD patients (19 female, 68%, mean age: 58.3±4.6 years, average office BP: 139/81±16/13 mmHg). In the group of patients with angina, MVD was defined by a standardized systematic protocol in which coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. MVD patients were classified into 2 groups, structural and functional endotype, based on commonly used cut-offs (impaired CFR &lt; 2.5, increased IMR &gt; 25). In addition, in all participants, arterial stiffness was assessed using the aortic augmentation index (AIx), derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the radial artery. Results: In the MVD group, the coronary flow reserve (CFR) was 1.4±0.9 and the index of microvascular resistance (IMR) was 43.9±30 IU. Of the 28 patients with impaired CFR, 8 (28%) had normal IMR consistent with functional CMD endotype, and 20 (71%) had abnormal IMR associated with structural alterations of the microvasculature. AIx was found to be increased in MVD patients compared to hypertensives (35.4±10.8 vs 27.4±12.6%, p = 0.031). This difference in AIx between the CMD and asymptomatic hypertensive controls was found to be statistically significant after adjustment for gender and age (p&lt;0.05). No statistically significant difference was found in body mass index, renal function, history of dyslipidemia, diabetes mellitus, and smoking between groups. Conclusions: Arterial stiffness was found to be increased in patients with MVD compared to asymptomatic hypertensive individuals. These results suggest that therapies targeting vascular stiffening could provide additional clinical benefit in patients with impaired coronary microvasculature.