Relation Between Coronary Tortuosity and Vasomotor Dysfunction in Patients Without Obstructed Coronaries?

Background: A large proportion of patients with angina and no obstructive coronary artery disease (ANOCA) has underlying coronary vasomotor dysfunction (CVDys), which can be diagnosed by a coronary function test (CFT). Coronary tortuosity is a common angiographic finding during the CFT. Yet, no data exist on the association between vasomotor dysfunction and coronary tortuosity.Aim: To investigate the association between CVDys and coronary tortuosity in patients with ANOCAMethods: All consecutive ANOCA patients who underwent clinically indicated CFT between February 2019 and November 2020 were included. CFT included acetylcholine spasm testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose microvascular dysfunction (MVD). MVD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) <2.0. Coronary tortuosity, was scored (no, mild, moderate or severe) based on the angles of the curvatures in the left anterior descending (LAD) artery on angiography.Results: In total, 228 patients were included (86% female, mean age 56 ± 9 years). We found coronary artery spasm in 81% of patients and MVD in 45% of patients (15%: abnormal CFR, 30%: abnormal IMR). There were 73 patients with no tortuosity, 114 with mild tortuosity, 41 with moderate tortuosity, and no patients with severe tortuosity. No differences were found in cardiovascular risk factors or medical history, and the prevalence of CVDys did not differ between the no tortuosity, mild tortuosity and moderate tortuosity group (82, 82, and 85%, respectively).Conclusion: In this study, CVDys was not associated with coronary tortuosity. Future experimental and clinical studies on the complex interplay between coronary tortuosity, wall shear stress, endothelial dysfunction and coronary flow are warranted.

Role of sex hormones in modulating myocardial perfusion and coronary flow reserve

Background A growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR. Methods Rest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [18F]flurpiridaz in a total of 56 mice (7–8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [18F]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFRApp) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging. Results Orchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 ± 1.0 vs. 22.2 ± 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 ± 1.2 vs. 27.3 ± 1.2 % ID/mL, p = 0.896). Accordingly, CFRApp was substantially higher in orchiectomized males (Gx vs. sham, 1.43 ± 0.04 vs. 1.23 ± 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFRApp (r = −0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females. Conclusion Our experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients.

Change in Computed Tomography-Derived Fractional Flow Reserve Across the Lesion Improve the Diagnostic Performance of Functional Coronary Stenosis

Aims: This study sought to evaluate the diagnostic performance of change in computed tomography-derived fractional flow reserve (CT-FFR) across the lesion (ΔCT-FFR) for identifying ischemia lesions with FFR as the reference standard.Methods: Patients who underwent coronary CT angiography (CCTA) and FFR measurement within 1 week from December 2018 to December 2019 were retrospectively enrolled. CT-FFR within 2 cm distal to the lesion, ΔCT-FFR and plaque characteristics were analyzed. The diagnostic accuracy of CCTA (coronary stenosis ≥ 50%), CT-FFR ≤ 0.80, and ΔCT-FFR ≥ 0.15 (based on the largest Youden index) were assessed with FFR as the reference standard. The relationship between plaque characteristics and ΔCT-FFR was analyzed.Results: The specificity of ΔCT-FFR and CT-FFR were 70.8 and 67.4%, respectively, which were both higher than CCTA (39.3%) (both P < 0.001), while there were no statistical significance in sensitivity among the three (84.5, 77.4, 88.1%, respectively; P = 0.08). The area under the curves (AUCs) of ΔCT-FFR and CT-FFR were 0.803 and 0.743, respectively, which were both higher than that of CCTA (0.637) (both P < 0.05), and the AUC of ΔCT-FFR was higher than that of CT-FFR (P < 0.001). Multivariable analysis showed that low-attenuation plaque (LAP) volume (odds ratio [OR], 1.006) and plaque length (OR, 1.021) were independently correlated with ΔCT-FFR (both P < 0.05).Conclusions: CT-FFR and ΔCT-FFR and here especially the ΔCT-FFR could improve the diagnostic performance of ischemia compared with CCTA alone. LAP volume and plaque length were the independent risk factors of ΔCT-FFR.

Case Report: Combination of Pressure Guidewire and Optical Coherence Tomography-Guided Drug-Coated Balloon Revascularization for Renal Artery Fibromuscular Dysplasia

Fibromuscular dysplasia (FMD) is the second common cause of renovascular hypertension. With the advent of endovascular therapy, angiography has become a diagnostic gold standard for FMD. Optical coherence tomography (OCT) by reflecting in vivo histology may improve diagnostic and classification accuracy. Renal fractional flow reserve (rFFR), measured by pressure guidewire, may distinguish the patients who may benefit from revascularization by identifying physiologically significant stenoses. However, the role of usage of both OCT and rFFR is not well-studied. We herein report a 17-year-old male with renovascular hypertension due to FMD. Angioplasty of drug-coated balloon (DCB) guided by OCT and FFR favorably achieved blood pressure (BP) control. In conclusion, the utility of both OCT and FFR may be useful for the appropriate selection of patients with renal FMD.

Impaired coronary flow reserve in patients with supra-normal left ventricular ejection fraction at rest

Purpose Recently, a “U” hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar “U” curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%). Methods Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated 13 N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose–response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan–Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome. Results An inverted “U” curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF < 55%) (n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF < 65%) (n = 106) (57.9% vs 54.5% vs 34.3%, p < 0.01, respectively). Both snLVEF (p < 0.01) and rLVEF (p < 0.05) remained independent predictors for reduced cCFR after multivariable adjustment. Patients with snLVEF encountered more MACE than those with nLVEF (10.5% vs 0.9%, log-rank p = 0.01). Conclusions Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.

Effect of Coronary Calcification Severity on Measurements and Diagnostic Performance of CT-FFR With Computational Fluid Dynamics: Results From CT-FFR CHINA Trial

Aims: To explore the effect of coronary calcification severity on the measurements and diagnostic performance of computed tomography-derived fractional flow reserve (FFR; CT-FFR).Methods: This study included 305 patients (348 target vessels) with evaluable coronary calcification (CAC) scores from CT-FFR CHINA clinical trial. The enrolled patients all received coronary CT angiography (CCTA), CT-FFR, and invasive FFR examinations within 7 days. On both per-patient and per-vessel levels, the measured values, accuracy, and diagnostic performance of CT-FFR in identifying hemodynamically significant lesions were analyzed in all CAC score groups (CAC = 0, &gt; 0 to &lt;100, ≥ 100 to &lt;400, and ≥ 400), with FFR as reference standard.Results: In total, the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under receiver operating characteristics curve (AUC) of CT-FFR were 85.8, 88.7, 86.9, 87.8, 87.1%, 0.90 on a per-patient level and 88.3, 89.3, 89.5, 88.2, 88.9%, 0.88 on a per-vessel level, respectively. Absolute difference of CT-FFR and FFR values tended to elevate with increased CAC scores (CAC = 0: 0.09 ± 0.10; CAC &gt; 0 to &lt;100: 0.06 ± 0.06; CAC ≥ 100 to &lt;400: 0.09 ± 0.10; CAC ≥ 400: 0.11 ± 0.13; p = 0.246). However, no statistically significant difference was found in patient-based and vessel-based diagnostic performance of CT-FFR among all CAC score groups.Conclusion: This prospective multicenter trial supported CT-FFR as a viable tool in assessing coronary calcified lesions. Although large deviation of CT-FFR has a tendency to correlate with severe calcification, coronary calcification has no significant influence on CT-FFR diagnostic performance using the widely-recognized cut-off value of 0.8.