Hyperemic Flow Research Articles

Diagnostic Yield of Comprehensive Coronary Function Testing in Patients with Angina and Unobstructed Coronary Arteries: Endotype Characterisation and Clinical Implications

Background: Coronary functional disorders (CFD) are significant contributors to angina with non-obstructed coronary arteries (ANOCA). Various endotypes, such as epicardial or microvascular spasm and/or coronary microvascular dysfunction (CMD), have been identified. Previous studies have shown a high prevalence of CFD in ANOCA cases, but often lacked comprehensive coronary functional testing (CFT), which ideally includes coronary spasm provocation testing and CMD assessment. This study aims to investigate the prevalence of CFD and to characterise endotypes in ANOCA patients using comprehensive CFT. Methods: A total of 89 consecutive ANOCA patients (mean age 64, 69% women) who underwent comprehensive CFT were enrolled. CFT comprised acetylcholine (ACh) spasm provocation testing and assessment of coronary flow reserve (CFR) and hyperaemic microvascular resistance using Doppler technique. Results: CFT identified at least one coronary vasomotion disorder in 91% of patients with ANOCA. Among them, microvascular spasm was the most common endotype (61%), followed by CMD (43%). Only 9% of patients had isolated CMD with the remaining CMD patients also showing coronary spasm. Low CFR was mainly associated with high resting coronary flow rather than impaired hyperaemic flow (R −0.60, p<0.0001). Additionally, 48% of patients with microvascular spasm exhibited moderate to severe coronary tortuosity. Conclusion: CFT provides a high diagnostic yield of CFD in ANOCA patients. Coronary spasm, particularly microvascular spasm, is the most frequent endotype. Patients with isolated CMD are rare, highlighting the importance of spasm testing in the ANOCA population.

Prognostic Value of Coronary Flow Capacity by 82Rb PET in Patients With Suspected Coronary Artery Disease and Normal Myocardial Perfusion at Semiquantitative Imaging Analysis.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and myocardial flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. We assessed the prognostic value of CFC derived from 82Rb positron emission tomography/computed tomography in patients with suspected coronary artery disease and normal myocardial perfusion imaging. We studied 1967 patients with suspected coronary artery disease and normal myocardial perfusion at the semiquantitative analysis of stress/rest cardiac 82Rb positron emission tomography/computed tomography imaging. Coronary artery calcium scores were calculated and categorized into 3 groups: 0, 0.1 to 99.9, and ≥100. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, mildly reduced CFC, minimally reduced CFC, or normal flow using previously defined thresholds. The outcome end points were myocardial infarction and cardiac death, whichever occurred first. During a mean time of 41±27 months, 49 events occurred (2.5% cumulative event rate, with an annualized event rate of 0.5% person-years). At multivariable Cox analysis, coronary artery calcium score categories and impaired CFC resulted as independent predictors of events (both P<0.001). The annualized event rate was higher in patients with impaired CFC compared with those with normal CFC (P<0.05). Kaplan-Meier analysis showed that patients with impaired CFC were at the highest risk of events. In patients with suspected coronary artery disease and normal myocardial perfusion, impaired CFC is associated with a higher risk of cardiac events. Evaluating CFC can help identify patients' candidates for additional therapies to prevent future events.

Coronary flow characteristics in cases with discordance between coronary flow reserve and the index of microvascular resistance in the assessment of coronary microvascular dysfunction

Abstract Background/Introduction Coronary flow reserve (CFR) and the index of microvascular resistance (IMR) are commonly used for the diagnosis of coronary microvascular dysfunction, but the two indices can reveal discordance. Purpose The aim of this study was to investigate the mechanisms of the discordance between CFR and IMR. Methods Haemodynamic data from patients who underwent invasive coronary functional assessment using a guidewire equipped with pressure and temperature sensors was analysed. We performed vessel-based analysis, and classified vessels with reference to the criteria of IMR ≥25 and CFR &amp;lt;2.0 as pathological into four groups: normal IMR/normal CFR (Group 1: G1), abnormal IMR/normal CFR (Group 2: G2), normal IMR/abnormal CFR (Group 3: G3), and abnormal IMR/abnormal CFR (Group 4: G4). Results Of 249 vessels form 176 patients, 82 (33%) were classified into G1, 28 (11%) into G2, 94 (38%) into G3, and 45 (18%) into G4. Median and interquartile ranges of IMR of the four groups were 14.3 [10.7–18.9], 34.2 [29.8–45.1], 16.9 [12.7–19.7], and 30.7 [28.4–43.5] (P &amp;lt;0.001), respectively, and those of CFR were 3.21 [2.48–4.29], 2.73 [2.34–3.03], 1.27 [1.06–1.55], and 1.28 [1.07–1.67] (P &amp;lt;0.001), respectively (Figure). In G2, hyperemic flow velocity was as low as G4 (1.97 [1.47–2.29] vs. 1.95 [1.41–2.50] sec-1, P=1.00), and the baseline flow velocity was lower than G4 (0.71 [0.49–0.85] vs. 1.44 [0.93–1.96] sec-1, P &amp;lt;0.001), leading to apparently normal CFR despite the diminished hyperemic flow. In G3, the hyperemic (3.60 [2.77–4.73] vs. 1.95 [1.41–2.50] sec-1, P &amp;lt;0.001) and the baseline flow velocity (2.85 [2.19–3.92] vs. 1.44 [0.93–1.96] sec-1, P &amp;lt;0.001) were higher than G4, leading to apparently decreased CFR despite the maintained hyperemic flow. Conclusion(s) The discordance between IMR and CFR can be explained by decreased coronary flow in abnormal IMR/normal CFR, and by increased baseline coronary flow in normal IMR/abnormal CFR.

A practical risk model based on Lasso-Cox regression for angina with nonobstructive coronary arteries (ANOCA) patients

Abstract Background Coronary flow reserve (CFR) reduction is currently one of the main criteria for risk-stratifying patients with angina and nonobstructive coronary artery disease (ANOCA). However, CFR depends on resting and vasodilated coronary hemodynamics, and a theoretical concern remains that physiological changes may inadvertently affect the result. Purpose We aim to fit different risk models for patients with ANOCA, which further provides applicable guidance to clinical doctors for their patients. Methods Between May 2018 and October 2023, 251 consecutive patients who were diagnosed as ANOCA were enrolled from Qilu Hospital of Shandong University, and the median follow-up was 800 (493, 1221) days. Demographic characteristics, cardiovascular risk factors, cardiac structure and function index, echocardiography-derived coronary flow velocity, coronary flow velocity-time integral, and CFR were collected. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses were used to screen for significant parameters that were included to develop a novel predictive nomogram model. Receiver operating characteristic curve and calibration curve were used to evaluate the performance and clinical utility of the nomogram. Results In LASSO regression selection, five variables, diabetes, global work efficiency (GWE), global wasted work (GWW), decreased hyperemic coronary flow velocity (&amp;lt;0.63m/s), and peak flow velocity-derived CFR&amp;lt;2.5 (Figure 1) showed their correlation to the occurrence of major adverse cardiovascular events (MACE). Univariate Cox regression analysis shows that diabetes (hazard ratio [HR] = 4.108; 95% confidence interval [CI], 2.296–7.350; p = 0.001), GWE (HR = 0.890; 95% CI, 0.856–0.926; p = 0.001), GWW (HR = 1.005; 95% CI, 1.004–1.007; p = 0.012), decreased hyperemic coronary flow velocity (HR =3.405; 95% CI, 1.730–6.702; p = 0.001) and peak flow velocity-derived CFR&amp;lt;2.5 (HR =3.456; 95% CI, 1.898–6.292; p = 0.001) were predictors of recurrent chest pain. Multivariate analysis showed that the association of diabetes (HR = 2.735; 95% CI, 1.452–5.152; p = 0.002), GWW (HR = 1.004; 95% CI, 1.001–1.007; p = 0.010), and peak flow velocity-derived CFR&amp;lt;2.5 (HR = 2.650; 95% CI, 1.306–5.380; p = 0.007) with MACE remained statistically significant after adjusting for other variables. A nomogram incorporated the predictors mentioned above; it is presented in Fig.2. Internal validation showed that the model has good predictive performance. The areas under the curve (AUCs) for prediction of the risk of MACE was 0.849 (Fig.3). The calibration curve for predicting chest pain recurrence shows a good agreement between prediction and observation (Fig.4). Conclusions Diabetes, GWE, GWW, decreased hyperemic coronary flow velocity (&amp;lt;0.63m/s), and peak flow velocity-derived CFR&amp;lt;2.5 are significant in identifying the occurrence risk of MACE for ANOCA patients.

Absolute coronary flow and microvascular resistance before and after TAVR

Abstract Purpose This study aims to investigate microcirculatory changes, both at rest and during hyperemia, using continuous intracoronary thermodilution, before TAVR, immediately post-TAVR, and at 6-month follow-up. Methods We included consecutive patients with high-gradient AS undergoing TAVR with non-obstructive coronary artery disease in the left anterior descending artery (LAD). Absolute coronary flow (Q) and microvascular resistance (R) were measured in the LAD using continuous intracoronary thermodilution at rest (Qrest) and during hyperemia (Qhyper) before and after TAVR, as well as at 6-month follow-up. Echocardiography and cardiac computed tomography (CCT) were used to quantify total myocardial mass and LAD-specific mass. Regional myocardial perfusion (QN) was calculated by dividing absolute coronary flow by the subtended myocardial mass. Results In 51 patients, absolute flow and microvascular resistance were assessed at rest and during hyperemia before and after TAVR. The mean age was 84.1 ± 5.0 years, and 35 participants were male (68.6%). Measurements were also obtained 6 months after TAVR in 20 (39%) patients. Overall, there were no significant changes in resting and hyperemic flow and resistance before and after TAVR (Qrest 68 [55-88] mL/min vs 69 [54 – 92] mL/min, p=0.776; Qhyper 158 [129 – 200] mL/min vs 172 [132, 216] mL/min, p=0.449, before and after TAVR, respectively). Consequently, coronary flow reserve (CFR) and microvascular resistance reserve (MRR) remained unchanged. At 6 months, there were no significant changes in flow and resistance both at rest and during hyperemia compared to baseline (Qrest: 72 [63-84] vs 83 [59-108] mL/min, p=0.658; Qhyper: 181 [158-200] vs 194 [167-222] mL/min, p=0.492; pre-TAVR and at 6 months follow-up, respectively), resulting in unchanged CFR and MRR. However, at follow-up, there was a noteworthy reduction in left ventricular mass of approximately 13% (from 201.9 ± 37.9g to 175.1 ± 46.6 g, p&amp;lt;0.001), leading to an increase in hyperemic perfusion (QN,hyper: 0.86 [0.69-1.06] vs 1.20 [0.99-1.32] mL/min/g, p=0.008; pre-TAVR and follow-up, respectively), but not in resting perfusion (QN, rest: 0.34 [0.30-0.48] vs 0.47 [0.36-0.67] mL/min/g, p=0.06). Conclusion Immediately after TAVR, there are no changes in absolute coronary flow and coronary flow reserve. Over time, LV remodeling is associated with increased hyperemic perfusion, indicating that, in the context of the observed pathophysiological changes in coronary microcirculation in AS patients after TAVR, the reverse LV remodeling has a more significant impact than the acute LV unloading achieved by valve replacement itself.

Determinants of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling, assessed by echocardiography, is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Our objective was to identify what are the determinants of this parameter in patients with hypertrophic cardiomyopathy (HCM). Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. Univariable linear regression analysis showed that age, maximal wall thickness, E/E’, indexed left atrial volume (LAVi), CFR-LAD, %LGE and % hypoperfusion (by CMR) were correlated with RV-PA uncoupling. The HCM phenotype or the presence of obstruction were not associated with uncoupling. Multivariable stepwise linear regression analysis showed that the independent predictors of RV-PA uncoupling were age (b-estimate: - 0.180, p=0.009), LAVi (b-estimate: -0.645, p=&amp;lt;0.001), CFR-LAD (b-estimate: 0.183, p=0.011) and %LGE (b-estimate: -0.270, p=&amp;lt;0.001). Conclusion In patients with HCM, the presence of coronary microcirculation abnormalities and the extent of LGE in the LV are independent predictors of RV-PA uncoupling.

The influence of epicardial resistance on Microvascular Resistance Reserve (MRR)

Abstract Background The optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance. Purpose We tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function. Methods In a cohort of 16 patients that had undergone proximal left anterior descending artery stenting, we created four grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) in order to assess their response to changing epicardial resistance. Results Graded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ±0.05; mild: 0.72 ±0.04; moderate: 0.61 ±0.05; severe: 0.48 ±0.09, p&amp;lt;0.001). This translated into a linear decrease in mean hyperaemic coronary flow (no stenosis: 170.5 ±66.8 ml/min; mild: 149.8 ±58.8 ml/min; moderate: 124.4 ±53.0 ml/min; severe: 94.0 ±45.2 ml/min, p&amp;lt;0.001) (Figure 1). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ±0.9; mild: 2.2 ±0.8; moderate: 1.8 ±0.7; severe: 1.4 ±0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (p&amp;lt;0.001). Conversely, MRR exhibited a minimal decrease across all stenosis grades (no stenosis: 3.0 ±1.0; mild: 3.0 ±1.0; moderate: 2.9 ±1.0; severe: 2.8 ±1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (p&amp;lt;0.001) (Figure 1). Conclusion MRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the most specific index of microvascular function.Figure 1.Absolute blood flow (Q) vs FFRFigure 2.MRR/CFR vs FFR

Artificial intelligence-based automated plaque quantification from CCTA to predict acute coronary syndrome on top of obstructive or ischemic coronary artery disease

Abstract Background Artificial intelligence (AI)-based quantitative computed tomography (AI-QCT) is a novel tool for automated plaque characterization and quantification from coronary computed tomography angiography (CCTA). The prognostic value of various AI-QCT plaque types on top of the presence of obstructive or ischemic coronary artery disease (CAD) is unknown. Purpose To investigate the added prognostic value for acute coronary syndrome (ACS) of AI-QCT total plaque burden (percent atheroma volume (PAV) %), and its subcomponents non-calcified plaque burden (NCPB), low-attenuation plaque burden (LAP), and calcified plaque burden (CPB) (%) on top of obstructive or ischemic CAD. Methods A cohort of 2007 symptomatic patients having undergone CCTA and selective downstream PET perfusion for suspected CAD was analyzed. Patients with prior or early elective revascularization within 6 months from CCTA were excluded. Obstructive CAD was defined as ≥1 vessel with &amp;gt;50% visual stenosis, and ischemic CAD as absolute hyperemic myocardial blood flow ≤2.3 ml/g/min in ≥2 adjacent segments on 15O-H2O PET. Multivariable Cox regressions adjusted for clinical confounders (age, sex hypertension, typical angina) including each plaque type separately (per 1.0%) on top of obstructive or ischemic CAD, respectively, were performed. The amount of LAP was &amp;lt;1% and therefore pooled together with NCPB. Results Throughout a median follow-up of 7 years, 72/2007 patients experienced ACS (50 myocardial infarction, 22 unstable angina). On top of obstructive CAD, all plaque types were independent predictors of ACS (Figure 1A), however according to the C-indexes (p-value vs. obstructive CAD), only PAV (C-index=0.814, p=0.010) and NCPB+LAP (C-index=0.818, p=0.014), but not CPB (C-index=0.800, p=0.066) significantly improved the prediction of ACS on top of obstructive CAD (C-index=0.790) (Figure 2A). On top of ischemic CAD (1967 patients, 66 events), all plaque types were also independent predictors of ACS (Figure 1B). But, similarly, according to the C-indexes (p-value vs. ischemic CAD), only PAV (C-index=0.818, p=0.003), and NCPB+LAP (C-index=0.818, p=0.005), but not CPB (C-index=0.798, p=0.054) significantly improved the prediction of ACS on top of ischemic CAD (C-index=0.776) (Figure 2B). NCPB+LAP alone performed similarly as PAV on top of obstructive (p=0.554) and ischemic CAD (p=0.991) (Figure 2). Conclusions Among patients with native coronary arteries treated medically, AI-based plaque quantification significantly improved the prediction of ACS on top of obstructive or ischemic CAD. The risk of ACS was largely related to NCPB+LAP, whereas CPB did not significantly improve risk stratification.Adjusted HR for ACS per plaque typeC-indexes for ACS

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= &amp;lt;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.

Coronary microvascular dysfunction in heart failure: observations from the MICRO registry

Abstract Background Heart failure (HF) is one of the leading causes of hospitalization in the elderly. Coronary microvascular dysfunction (CMD), among other risk factors, is linked to the pathogenesis and clinical manifestations of HF. Purpose This abstract aims to summarize key findings from a comprehensive analysis of CMD in subgroups of HF, shedding light on its association with hemodynamic parameters. Methods Patients experiencing recurrent angina (CCS II-IV) and no relevant epicardial stenosis were enrolled in a prospective registry (MICRO). Epicardial and microvascular responses (pressure, resistance and flow) were assessed at rest and during adenosine and acetylcholine testing. The impact of an elevated left ventricular end-diastolic pressure (LVEDP) in the absence of clinical signs of HF was also investigated. Results Overall, 188 patients (63% (118) women, mean age 65±11 years) with angina and no epicardial stenosis were enrolled. Patients with HF (n=26) displayed lower hyperemic flow in response to endothelium-independent adenosine (5.2±3.1 vs. 7.3±4.4; P=0.004), lower coronary flow reserve (2.9±1.5 vs. 4.4±1.1; P&amp;lt;0.001) and microvascular resistance reserve (3.3±2.1 vs. 5.2±2.7; P&amp;lt;0.001), and increased microvascular resistance during adenosine-induced hyperemia (25±21 vs. 17±11; P=0.045). An increased LVEDP without clinical signs of HF was not associated with a lower coronary flow reserve (4.3±1.9 vs. 2.6±1.2; P=0.006) or microvascular resistance reserve (4.9±2.1 vs. 2.8±1.7; P=0.004). Microvascular resistance during acetylcholine (endothelium-dependent)-induced hyperemia was lower in HF patients (36.2±23.5 vs. 57.4±37.8; P=0.018). Conclusion(s) Patients with heart failure displayed signs of impaired microvascular endothelium-independent responses while endothelium-dependent reactivity appears to be maintained. An elevated LVEDP without clinical HF was not associated with impaired coronary microvascular function.

7143 Near Term Cardiometabolic Outcomes in Transgender Boys and Men in the First Year of Gender-Affirming Testosterone Therapy

Abstract Disclosure: J. Dey: None. M. Widlansky: None. S. Cabrera: None. Background: Gender affirming testosterone (T) therapy is used to masculinize transgender adolescent men (TMs), resulting in elevated T and suppressed estradiol (E2). In cis-females, hypoestrogenism reduces vaso-protective E2-mediated estrogen receptor expression, decreasing nitric oxide vasodilation and increasing susceptibility to future vascular complications. Whether T promotes similar changes in TMs remains poorly understood. Methods: A longitudinal observational study is conducted in TMs aged 12-30yrs over the 1st yr of T, with visits at baseline (BL; pre-T), 6mo, and 1yr, compared to cis-males (CMs) with endogenous T. Primary outcome is change in brachial artery flow-mediated dilation (FMD%), an in vivo measure of vascular endothelial health, after 1yr of T. To detect a significant relative change in FMD%, 60 participants are needed (40 TMs, 20 CMs). Metabolic profile is assessed by fasting lipids, glucose, and insulin. Body composition is assessed by BMI and DEXA. Differences in mean values between and within a cohort were analyzed using the unpaired two-tailed T-test assuming unequal and equal variances, respectively. Results: To date, 51 participants are enrolled; the 21 participants who fully completed the study are included here (13 TMs, 8 CMs). At BL, TMs were post-menarchal with a mean age of 15.6yrs, ht 162.6cm, and BMI z-score 0.47. At BL, 46% were on progestin-only menstrual suppression. CMs had a mean age of 18.4yrs, ht 170.7cm, and BMI z-score 0.13. Cohorts were similar for age, height, and BMI.At BL, FMD% was higher in TMs than CMs (8.2 vs 4.6, p=0.01) but not at 1yr (6.9 vs 6.2, p=0.6). FMD% did not change in TMs receiving T over 1yr (8.2 vs 6.9, p=0.3). At BL, the brachial artery resting diameter (mm) was lower in TMs than CMs (2.6 vs 3.5, p&amp;lt;0.01) and remained such at 1-yr. Resting diameter increased in TMs over 1yr of T (2.6 vs 3.1, p&amp;lt;0.01) but not in CMs. There were no differences in resting or hyperemic flow velocity, or FMD (mm) between or within groups. At BL, % lean body mass (%LBM) was lower in TMs than CMs (60 vs 72, p&amp;lt;0.01) and estimated percent visceral adiposity tissue (%VAT) was higher (26 vs 14, p&amp;lt;0.01). In TMs, %LBM increased (60 vs 66, p &amp;lt;0.01) and %VAT decreased (26 vs 21, p&amp;lt;0.01) over 1yr of T, such that TMs and CMs were similar at 1yr. At BL, TMs had lower T but similar E2 (46 vs 27 pg/mL, p=0.2) to CMs. At 1-yr, TMs and CMs had similar T (556 vs 574 ng/dL, p=0.9) and E2 (52 vs 29, p=0.1). In TMs, T did not change E2. Lipid and glycemic indices did not change over 1yr in TMs. Conclusion: Initial analyses suggest that T does not affect FMD; however, FMD% interpretation is confounded by the small number of participants, progestins at BL in TMs, and the lower resting brachial artery diameter in TMs. The stable E2 in TMs on T may explain the stable FMD%. Overall, our findings suggest T results in relative stability of vascular and metabolic function and a beneficial shift in body composition in TMs. Presentation: 6/2/2024

Absolute coronary flow and microvascular resistance before and after transcatheter aortic valve implantation.

Severe aortic stenosis (AS) is associated with left ventricular (LV) remodelling, likely causing alterations in coronary blood flow and microvascular resistance. We aimed to evaluate changes in absolute coronary flow and microvascular resistance in patients with AS undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with AS undergoing TAVI with non-obstructive coronary artery disease in the left anterior descending artery (LAD) were included. Absolute coronary flow (Q) and microvascular resistance (Rμ) were measured in the LAD using continuous intracoronary thermodilution at rest and during hyperaemia before and after TAVI, and at 6-month follow-up. Total myocardial mass and LAD-specific mass were quantified by echocardiography and cardiac computed tomography. Regional myocardial perfusion (QN) was calculated by dividing absolute flow by the subtended myocardial mass. In 51 patients, Q and R were measured at rest and during hyperaemia before and after TAVI; in 20 (39%) patients, measurements were also obtained 6 months after TAVI. No changes occurred in resting and hyperaemic flow and resistance before and after TAVI nor after 6 months. However, at 6-month follow-up, a notable reverse LV remodelling resulted in a significant increase in hyperaemic perfusion (QN,hyper: 0.86 [interquartile range {IQR} 0.691.06] vs 1.20 [IQR 0.99-1.32] mL/min/g; p=0.008; pre-TAVI and follow-up, respectively) but not in resting perfusion (QN,rest: 0.34 [IQR 0.30-0.48] vs 0.47 [IQR 0.36-0.67] mL/min/g; p=0.06). Immediately after TAVI, no changes occurred in absolute coronary flow or coronary flow reserve. Over time, the remodelling of the left ventricle is associated with increased hyperaemic perfusion.

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.

Age-related structural remodelling of the coronary circulation.

While it is broadly accepted that ageing is associated with impairment of coronary microvascular function, little is known about the underlying mechanisms. We investigated age-related changes in coronary microvascular structure in patients with stable angina without epicardial coronary stenoses. In an analysis of the IDEAL registry, a total of 165 vessels without coronary stenosis were interrogated with combined pressure/Doppler guidewires. We calculated diastolic microvascular conductance (DMVC) and backward expansion wave (BEW), and compared them between age tertiles. We calculated the prevalence of CMD, defined by reduced coronary flow reserve (CFR), and the prevalence of low BEW and low DMVC in each group. The three study groups were defined as having 37-53, 54-66, and 67-77 years of age, respectively. Oldest (3rd tertile) patients showed lower hyperemic flow velocity (46.7 ± 14.4 vs. 45.1 ± 12.4 vs. 38.4 ± 11.5 cm s-1, p = 0.019), lower DMVC (1.90 ± 0.71 vs. 1.44 ± 0.56 vs. 1.37 ± 0.67 cm s-1 mmHg-1, p < 0.001) and lower BEW intensity (5.9 [2.9-8.4] vs. 4.8 [2.9-6.8] vs. 4.4 [3.4-6.3] × 106 W m-2 s-1, p = 0.094). Older age was independently associated with lower BEW intensity (B: -0.10, 95% confidence interval [CI]: -0.17 to -0.09, p = 0.021) and DMVC (B: -0.25 95% CI: -0.45 to -0.09, p = 0.027). In patients with CFR < 2.5, the prevalence of BEW intensity and DMVC below the 25th percentile increased with age (25.0% vs. 52.0% vs. 72.7%, p = 0.010). Ageing is independently associated with structural microcirculatory remodeling that is reflected in BEW intensity and DMVC measurements, and with an increased prevalence of structural CMD. These results are important to understand non-obstructive mechanisms of myocardial ischemia in the elderly.

Influence of the pressure wire on the fractional flow reserve calculation: CFD analysis of an ideal vessel and clinical patients with stenosis

Background and objectiveFractional Flow Reserve (FFR) is generally considered the gold standard in hemodynamics to assess the impact of a stenosis on the blood flow. The standard procedure to measure involves the displacement of a pressure guide along the circulatory system until it is placed next to the lesion to be analyzed. The main objective of the present study is to analyze the influence of the pressure guide on the invasive FFR measurements and its implications in clinical practice. MethodsWe studied the influence of pressure wires on the measurement of Fractional Flow Reserve (FFR) through a combination of Computational Fluid Dynamics (CFD) simulations using 45 clinical patient data with 58 lesions and ideal geometries. The analysis is conducted considering patients that were subjected to a computer tomography and also have direct measurements using a pressure guide. Influence of the stenosis severity, degree of occlusion and blood viscosity has also been studied. ResultsThe influence of pressure wires specifically affects severe stenosis with a lumen diameter reduction of 50 % or greater. This type of stenosis leads to reduced hyperemic flow and increased coronary pressure drop. Thus, we identified that the placement of wires during FFR measurements results in partial obstruction of the coronary artery lumen, leading to increased pressure drop and subsequent reduction in blood flow. The severity of low FFR values associated with severe stenosis may be prone to overestimation when compared to stenosis without severe narrowing. These results have practical implications, particularly in the interpretation of lesions falling within the “gray zone” (0,75−0,80). ConclusionsThe pressure wire's presence significantly alters the flow on severe lesions, which has an impact on the FFR calculation. In contrast, the impact of the pressure wire appears to be reduced when the FFR is larger than 0.8. The findings provide critical information for physicians, emphasizing the need for cautious interpretation of FFR values, particularly in severe stenosis. It also offers insights into improving the correlation between FFRct models and invasive measurements by incorporating the influence of pressure wires.

Modeling cardiac microcirculation for the simulation of coronary flow and 3D myocardial perfusion.

Accurate modeling of blood dynamics in the coronary microcirculation is a crucial step toward the clinical application of in silico methods for the diagnosis of coronary artery disease. In this work, we present a new mathematical model of microcirculatory hemodynamics accounting for microvasculature compliance and cardiac contraction; we also present its application to a full simulation of hyperemic coronary blood flow and 3D myocardial perfusion in real clinical cases. Microvasculature hemodynamics is modeled with a compliant multi-compartment Darcy formulation, with the new compliance terms depending on the local intramyocardial pressure generated by cardiac contraction. Nonlinear analytical relationships for vessels distensibility are included based on experimental data, and all the parameters of the model are reformulated based on histologically relevant quantities, allowing a deeper model personalization. Phasic flow patterns of high arterial inflow in diastole and venous outflow in systole are obtained, with flow waveforms morphology and pressure distribution along the microcirculation reproduced in accordance with experimental and in vivo measures. Phasic diameter change for arterioles and capillaries is also obtained with relevant differences depending on the depth location. Coronary blood dynamics exhibits a disturbed flow at the systolic onset, while the obtained 3D perfusion maps reproduce the systolic impediment effect and show relevant regional and transmural heterogeneities in myocardial blood flow (MBF). The proposed model successfully reproduces microvasculature hemodynamics over the whole heartbeat and along the entire intramural vessels. Quantification of phasic flow patterns, diameter changes, regional and transmural heterogeneities in MBF represent key steps ahead in the direction of the predictive simulation of cardiac perfusion.

Effects of age on microvascular function in patients with normal coronary arteries.

It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rμ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rμ (Rμ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rμ (Rμ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.

The Influence of Epicardial Resistance on Microvascular Resistance Reserve

BackgroundThe optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance. ObjectivesThe authors tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function. MethodsIn a cohort of 16 patients who had undergone proximal left anterior descending artery stenting, we created 4 grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) to assess their response to changing epicardial resistance. ResultsGraded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ± 0.05; mild: 0.72 ± 0.04; moderate: 0.61 ± 0.05; severe: 0.48 ± 0.09; P < 0.001). This translated into a linear decrease in mean hyperemic coronary flow (no stenosis: 170.5 ± 66.8 mL/min; mild: 149.8 ± 58.8 mL/min; moderate: 124.4 ± 53.0 mL/min; severe: 94.0 ± 45.2 mL/min; P < 0.001). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ± 0.9; mild: 2.2 ± 0.8; moderate: 1.8 ± 0.7; severe: 1.4 ± 0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (P < 0.001). In contrast, MRR exhibited a negligible decrease across all stenosis grades (no stenosis: 3.0 ± 1.0; mild: 3.0 ± 1.0; moderate: 2.9 ± 1.0; severe: 2.8 ± 1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (P < 0.001). ConclusionsMRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the more specific index of microvascular function. This suggests that MRR can also reliably evaluate microvascular function in patients with significant epicardial disease.

Determining Hemodynamically Significant Coronary Artery Disease: Patient-Specific Cutoffs in Quantitative Myocardial Blood Flow Using [15O]H2O PET Imaging.

Currently, cutoffs of quantitative [15O]H2O PET to detect fractional flow reserve (FFR)-defined coronary artery disease (CAD) were derived from a single cohort that included patients without prior CAD. However, prior CAD, sex, and age can influence myocardial blood flow (MBF). Therefore, the present study determined the influence of prior CAD, sex, and age on optimal cutoffs of hyperemic MBF (hMBF) and coronary flow reserve (CFR) and evaluated whether cutoff optimization enhanced diagnostic performance of quantitative [15O]H2O PET against an FFR reference standard. Methods: Patients with chronic coronary symptoms underwent [15O]H2O PET and invasive coronary angiography with FFR. Optimal cutoffs for patients with and without prior CAD and subpopulations based on sex and age were determined. Results: This multicenter study included 560 patients. Optimal cutoffs were similar for patients with (n = 186) and without prior CAD (hMBF, 2.3 vs. 2.3 mL·min-1·g-1; CFR, 2.7 vs. 2.6). Females (n = 190) had higher hMBF cutoffs than males (2.8 vs. 2.3 mL·min-1·g-1), whereas CFRs were comparable (2.6 vs. 2.7). However, female sex-specific hMBF cutoff implementation decreased diagnostic accuracy as compared with the cutoff of 2.3 mL·min-1·g-1 (72% vs. 82%, P < 0.001). Patients aged more than 70 y (n = 79) had lower hMBF (1.7 mL·min-1·g-1) and CFR (2.3) cutoffs than did patients aged 50 y or less, 51-60 y, and 61-70 y (hMBF, 2.3-2.4 mL·min-1·g-1; CFR, 2.7). Age-specific cutoffs in patients aged more than 70 y yielded comparable accuracy to the previously established cutoffs (hMBF, 72% vs. 76%, P = 0.664; CFR, 80% vs. 75%, P = 0.289). Conclusion: Patients with and without prior CAD had similar [15O]H2O PET cutoffs for detecting FFR-defined significant CAD. Stratifying patients according to sex and age led to different optimal cutoffs; however, these values did not translate into an increased overall accuracy as compared with previously established thresholds for MBF.

Ischemic Conditioning Improves the Microvascular Hyperemic Response to Passive Limb Movement in Young Adults

Background: Passive limb movement (PLM) of the lower extremity is a simple and clinically relevant approach to measure peripheral microvascular health. PLM causes an acute increase in hyperemic leg blood flow (LBF) without an increase in skeletal muscle metabolism, and the hyperemic response is ~80% nitric oxide-mediated. A known therapeutic stimulus to increase large conduit artery vascular health is ischemic conditioning (IC). Whether a single session of IC can improve the hyperemic response to PLM remains unknown. Objective: To quantify the microvascular response to PLM after a single session of IC in young adults. Hypothesis: The hyperemic response to PLM, measured as a change in peak femoral artery blood flow, will be greater following IC vs. sham-IC. Methods: This was a prospective, cross-over, blinded clinical trial (NCT05935670). Young adults aged 18-30 years who were free of cardiovascular disease were recruited, and study participants completed two study visits. Participants were seated in a Biodex dynamometer and superficial femoral artery resting blood flow and diameter were measured in the dominant leg using ultrasonography. The dynamometer then passively moved the knee 90 degrees at a frequency of 1 Hz for a single PLM while blood flow was continuously measured. The ΔLBF was calculated as the absolute (ml/min) and relative (% change) difference in LBF from rest to peak. Participants were then randomized to receive either IC or sham-IC, and the vascular assessor was blinded to the condition. For IC, the cuff was placed around the proximal dominant thigh and repetitively inflated to 225 mmHg for 5 min then deflated for 5 min, for a total of 5 cycles. For sham-IC, the thigh cuff was inflated to only 25 mmHg. Fifteen minutes after IC or sham-IC the hyperemic response to PLM was re-assessed. The pre-/post- change in the PLM hyperemic response was calculated as the difference from pre- vs. post-IC or sham-IC. Statistical analysis included one-sided paired t-tests. Results: Seven individuals (3 female, age 26 ± 4 years old) completed the study. Compared to pre-IC, the relative peak hyperemic response to PLM was augmented post-IC (%ΔLBF = 89 ± 42% pre- vs. 136 ± 49% post-IC, p=0.001). Conversely, there was no change in the relative peak hyperemic response in the sham-IC condition (%ΔLBF = 108 ± 61% pre- vs. 108 ± 77% post-sham-IC, p=0.50). The pre-/post- change score of absolute peak hyperemic response to PLM was also higher after IC vs. sham-IC (change in ΔLBF = 50 ± 78 IC ml/min vs. -44 ± 127 ml/min sham-IC, p = 0.03). Conclusion: These results show an improvement in the peripheral microvascular response to PLM following IC. Future studies should examine the mechanistic pathways responsible for an improved PLM response as well as the potential benefits of IC on microvascular health in clinical populations with underlying peripheral microvascular dysfunction. AAW was supported by the National Heart, Lung and Blood Institute (T32HL13464) and Cardiovascular Center’s A.O. Smith Fellowship Scholars Program. Research was supported by the Eunice Kennedy Shriver National Institute of Child Health &amp; Human Development R01-HD099340 (ASH and MJD) and R01-HD112258 (MJD and ASH). This is the full abstract presented at the American Physiology Summit 2024 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.