Coronary Flow Reserve, Inflammation, and Myocardial Strain: The CIRT-CFR Trial.

Inflammation is a key determinant of cardiovascular outcomes, but its role in heart failure is uncertain. In patients with cardiometabolic disease enrolled in the prospective, multicenter ancillary study of CIRT (Cardiovascular Inflammation Reduction Trial), CIRT-CFR (Coronary Flow Reserve to Assess Cardiovascular Inflammation), impaired coronary flow reserve was independently associated with increased inflammation and myocardial strain despite well-controlled lipid, glycemic, and hemodynamic profiles. Inflammation modified the relationship between CFR and myocardial strain, disrupting the association between cardiac blood flow and function. Future studies are needed to investigate whether an early inflammation-mediated reduction in CFR capturing microvascular ischemia may lead to heart failure in patients with cardiometabolic disease. (Cardiovascular Inflammation Reduction Trial [CIRT]; NCT01594333; Coronary Flow Reserve to Assess Cardiovascular Inflammation [CIRT-CFR]; NCT02786134).

Serial changes of coronary flow reserve over one year after transcatheter aortic valve implantation in patients with severe aortic stenosis.

Background: Impaired coronary flow reserve (CFR) portends a poor prognosis in patients with aortic stenosis. The present study aims to investigate how CFR changes over one year after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis, and to explore factors related to the changes. Methods: Consecutive patients undergoing TAVI were registered. CFR in the left anterior descending artery was measured by transthoracic echocardiography on three occasions pre-TAVI, one-day post-TAVI, and one-year post-TAVI. Results: A total of 59 patients were enrolled, 46 of whom completed one-year follow-up. CFR was impaired in 35 (59.3%) patients pre-TAVI, but the impairment was only seen in 2 patients (4%) one-year post-TAVI. CFR value improved from 1.75 (1.50-2.10) cm/s pre-TAVI, to 2.00 (1.70-2.30) one-day post-TAVI, and further to 2.60 (2.30-3.10) one-year post-TAVI (P < 0.001). The median difference in CFR between pre-TAVI and one-year post-TAVI was 0.90 (0.53-1.20). Patients with significant improvement of CFR (more than the median value of 0.9) had larger aortic valve area (1.55 [1.38-1.92] vs. 1.36 cm2 [1.26-1.69], P = 0.042) and greater improvement in left ventricular ejection fraction (3.10 [-1.67-4.24] vs. -1.46 [-3.42-1.48] percentage points, P = 0.019) than those without. Conclusions: CFR is impaired in a considerable proportion of patients with severe aortic stenosis, but improvement is seen immediately after TAVI, and one year later. Patients with significant improvement of CFR had larger aortic valve area and greater increase in left ventricular ejection fraction after TAVI.

Effect of Atorvastatin on Serial Changes in Coronary Physiology and Plaque Parameters.

Background: The effects of statin on coronary physiology have not been well evaluated. Objectives: The authors performed this prospective study to investigate changes in coronary flow indexes and plaque parameters, and their associations with atorvastatin therapy in patients with coronary artery disease (CAD). Methods: Ninety-five patients with intermediate CAD who received atorvastatin therapy underwent comprehensive physiological assessments with fractional flow reserve (FFR), coronary flow reserve, index of microcirculatory resistance, and intravascular ultrasound at the index procedure, and underwent the same evaluations at 12-month follow-up. Optimal low-density lipoprotein cholesterol (LDL-C) was defined as LDL-C <70 mg/dL or ≥50% reduction from the baseline. The primary endpoint was a change in the FFR. Results: Baseline FFR, minimal lumen area, and percent atheroma volume (PAV) were 0.88 ± 0.05, 3.87 ± 1.28, 55.92 ± 7.30, respectively. During 12 months, the percent change in LDL-C was -33.2%, whereas FFR was unchanged (0.87 ± 0.06 at 12 months; P = 0.694). Vessel area, lumen area, and PAV were significantly decreased (all P values <0.05). The achieved LDL-C level and the change of PAV showed significant inverse correlations with the change in FFR. In patients with optimally modified LDL-C, the FFR had increased (0.87 ± 0.06 vs 0.89 ± 0.07; P = 0.014) and the PAV decreased (56.81 ± 6.44% vs 55.18 ± 8.19%; P = 0.031), whereas in all other patients, the FFR had decreased (0.88 ± 0.05 vs 0.86 ± 0.06; P = 0.025) and the PAV remained unchanged. Conclusions: In patients with CAD, atorvastatin did not change FFR despite a decrease in the PAV. However, in patients who achieved the optimal LDL-C target level with atorvastatin, the FFR had significantly increased with decrease of the PAV. (Effect of Atorvastatin on Fractional Flow Reserve in Coronary Artery Disease [FORTE]; NCT01946815).

Association Between Thrombogenicity Indices and Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction.

The association between thrombogenicity and coronary microvascular dysfunction (CMD) has been poorly explored in patients with acute myocardial infarction (AMI). In our real-world clinical practice (N = 116), thrombogenicity was evaluated with thromboelastography and conventional hemostatic measures, and CMD was defined as index of microcirculatory resistance of >40 U using the invasive physiologic test. High platelet-fibrin clot strength (P-FCS) (≥68 mm) significantly increased the risk of postprocedural CMD (odds ratio: 4.35; 95% CI: 1.74-10.89). Patients with both CMD and high P-FCS had a higher rate of ischemic events compared to non-CMD subjects with low P-FCS (odds ratio: 5.58; 95% CI: 1.31-23.68). This study showed a close association between heightened thrombogenicity and CMD and their prognostic implications after reperfusion in acute myocardial infarction patients.

Aging increases circulating BH2 without modifying BH4 levels and impairs peripheral vascular function in healthy adults.

Little is known about the mechanisms of aging on vascular beds and its relationship with tetra and di-hydrobiopterin (BH4 and BH2) levels. This observational clinical study analyzed the impact of aging on plasma and platelet biopterins, cutaneous blood flow (CBF), and coronary flow reserve (CFR) in healthy adults. The study enrolled healthy adults in 3 age groups: 18-30, 50-59, and 60-70 years (n = 25/group). Biopterins were assessed by LC-MS/MS using newly defined pre-analytical conditions limiting BH4 oxidation and improving long-term stability. CBF was measured by Laser Speckle Contrast Imaging coupled with acetylcholine-iontophoresis and CFR by adenosine stress cardiac magnetic resonance. In healthy adults, aging (60-70 years vs 18-30 years) significantly increased platelet BH2 (+75%, P = 0.033) and BH2 + BH4 (+31%, P = 0.033), and to a lesser extent plasma BH2 (+29%, P = 0.009) without affecting BH4 and BH4/BH2. Simultaneously, CBF was decreased (-23%, P = 0.004) but not CFR, CBF being inversely correlated with platelet BH2 (r = -0.42, P = 0.001) and BH2 + BH4 (r = -0.41, P = 0.002). The proportion of adults with abnormal platelet BH2 increased with age (+28% in 60-70y). These abnormal BH2 levels were significantly associated with reduced CBF and CFR (-16%, P = 0.03 and -26%, P = 0.02). In conclusion, our study showed that age-related peripheral endothelial dysfunction was associated with an increase in circulating BH2 without decreasing BH4, the effect being more marked in platelets, the most relevant blood compartment to assess biopterin bioavailability. Peripheral but not coronary vascular function is progressively impaired with aging in healthy adults. All these findings support biopterins as therapeutic targets to improve vascular function.

Coronary Microvascular Spasm as the Underlying Cause of the Angiographic Slow Flow Phenomenon.

Slow coronary flow is frequently seen during angiography in patients with angina and unobstructed coronary arteries. However, the pathophysiology of this finding remains largely unclear. We report a case of a 52-year-old woman with slow coronary flow caused by acetylcholine-induced microvascular spasm, as confirmed by intracoronary flow measurements. (Level of Difficulty: Beginner.).

Therapeutic Antibody Against Phosphorylcholine Preserves Coronary Function and Attenuates Vascular 18F-FDG Uptake in Atherosclerotic Mice.

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of 18F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.

Clinical usefulness of instantaneous wave-free ratio for the evaluation of coronary artery lesion with prior myocardial infarction: A multi-center study.

BACKGROUND: Fractional flow reserve (FFR) is useful for assessing the functional significance of coronary artery stenosis, even in lesions with prior myocardial infarction (pMI). Instantaneous wave-free ratio (iFR) is a vasodilator-free alternative for the physiological assessment of coronary artery stenosis. In addition, iFR shows good diagnostic agreement with FFR and an iFR-guided revascularization strategy was non-inferior to an FFR-guided revascularization strategy. However, the clinical usefulness of iFR for the evaluation of a coronary artery lesions with pMI has not been evaluated. METHODS AND RESULTS: A total of 200 lesions from 200 patients (44 pMI territories lesions and 156 non-pMI coronary artery lesions) were analyzed retrospectively. Major adverse cardiac events (MACE) were defined as cardiovascular death, non-fatal MI, unstable angina pectoris, fatal arrhythmia and heart failure during 12 months follow-up after the physiological assessment of coronary artery stenosis. iFR was closely correlated with FFR in pMI and non-pMI lesions (r = 0.81 and 0.72; P < 0.001, respectively). In pMI lesions, an iFR cut-off of 0.89 was optimal against a clinical FFR cut-off of 0.80 according to receiver operating characteristics (ROC) curve analysis, whereas in non-pMI lesions, the iFR cut-off value was 0.92 without statistical significance. In addition, the event rate of MACE was similar between pMI and non-pMI patients during follow-up even in the presence or absence of an PCI procedure. CONCLUSIONS: iFR may be a useful alternative method compared with FFR for clinical decision-making even in pMI patients.

Automated calcium scores collected during myocardial perfusion imaging improve identification of obstructive coronary artery disease.

BACKGROUND: Myocardial perfusion imaging (MPI) is an accurate noninvasive test for patients with suspected obstructive coronary artery disease (CAD) and coronary artery calcium (CAC) score is known to be a powerful predictor of cardiovascular events. Collection of CAC scores simultaneously with MPI is unexplored. AIM: We aimed to investigate whether automatically derived CAC scores during myocardial perfusion imaging would further improve the diagnostic accuracy of MPI to detect obstructive CAD. METHODS: We analyzed 150 consecutive patients without a history of coronary revascularization with suspected obstructive CAD who were referred for 82Rb PET/CT and available coronary angiographic data. Myocardial perfusion was evaluated both semi quantitatively as well as quantitatively according to the European guidelines. CAC scores were automatically derived from the low-dose attenuation correction CT scans using previously developed software based on deep learning. Obstructive CAD was defined as stenosis >70% (or >50% in the left main coronary artery) and/or fractional flow reserve (FFR) ≤0.80. RESULTS: In total 58% of patients had obstructive CAD of which seventy-four percent were male. Addition of CAC scores to MPI and clinical predictors significantly improved the diagnostic accuracy of MPI to detect obstructive CAD. The area under the curve (AUC) increased from 0.87 to 0.91 (p: 0.025). Sensitivity and specificity analysis showed an incremental decrease in false negative tests with our MPI + CAC approach (n = 14 to n = 4), as a consequence an increase in false positive tests was seen (n = 11 to n = 28). CONCLUSION: CAC scores collected simultaneously with MPI improve the detection of obstructive coronary artery disease in patients without a history of coronary revascularization.

Invasive physiological indices to determine the functional significance of coronary stenosis.

Physiological measurements are now commonly used to assess coronary lesions in the cardiac catheterisation laboratory, and this practice is evidence-based and supported by clinical guidelines. Fractional flow reserve is currently the gold standard method to determine whether coronary lesions are functionally significant, and is used to guide revascularization. There are however several other physiological measurements that have been proposed as alternatives to the fractional flow reserve. This review aims to comprehensively discuss physiological indices that can be used in the cardiac catheterisation laboratory to determine the functional significance of coronary lesions. We will focus on their advantages and disadvantages, and the current evidence supporting their use.

Assessment of Coronary Flow Reserve with Adenosine Triphosphate Compared to the Response to Adenosine

BACKGROUND: Previous studies have indicated adenosine triphosphate (ATP) is as potent coronary vasodillator as adenosine (A). We designed this study to compare the vasomotion of coronary artery (CA) between the infusion of ATP and that of A (1). METHOD AND RESULTS: Ten patients with normal CA (6 male and 4 female) age ranging from 41 to 74 years (57+/-11) were studied at LAD and RCA for measurement of coronary flow reserve (CFR), time to maximum effect (Tmax), time to baseline (TBL) in CA during ATP and A infusion. Tmax was achieved earlier with ATP than A, and these results suggest that maximum vasodilation occurs faster with ATP. Side effect profile was similar in 2 patients with mild chest pain with ATP and A. CONCLUSION: Since it has appeared that vasodilatory effect of ATP was comparable to A which has been used in pharmacological stress test in many diagnostic modalities, ATP can be used safely in many clinical setting where A has been used.