Study protocol for the epigenetic characterization of angor pectoris according to the affected coronary compartment: Global and comprehensive assessment of the relationship between invasive coronary physiology and microRNAs.

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs involved in post-transcriptional genetic regulation with a proposed role in intercellular communication. miRNAs are considered promising biomarkers in ischemic heart disease. Invasive physiological evaluation allows a precise assessment of each affected coronary compartment. Although some studies have associated the expression of circulating miRNAs with invasive physiological indexes, their global relationship with coronary compartments has not been assessed. Here, we will evaluate circulating miRNAs profiles according to the coronary pattern of the vascular compartment affectation. STUDY AND DESIGN: This is an investigator-initiated, multicentre, descriptive study to be conducted at three centres in Spain (NCT05374694). The study will include one hundred consecutive patients older than 18 years with chest pain of presumed coronary cause undergoing invasive physiological evaluation, including fractional flow reserve (FFR) and index of microvascular resistance (IMR). Patients will be initially classified into four groups, according to FFR and IMR: macrovascular and microvascular affectation (FFR≤0.80 / IMR≥25), isolated macrovascular affectation (FFR≤0.80 / IMR<25), isolated microvascular affectation (FFR>0.80 / IMR ≥25) and normal coronary indexes (FFR>0.80 / IMR<25). Patients with isolated microvascular affectation or normal indexes will also undergo the acetylcholine test and may be reclassified as a fifth group in the presence of spasm. A panel of miRNAs previously associated with molecular mechanisms linked to chronic coronary syndrome will be analysed using RT-qPCR. CONCLUSIONS: The results of this study will identify miRNA profiles associated with patterns of coronary affectation and will contribute to a better understanding of the mechanistic pathways of coronary pathology.

Intracoronary thrombus assessment with cardiac computed tomography angiography in a deferred stenting strategy: the MATURE prospective study (MSCT to Assess ThrombUs REsolution).

BACKGROUND: Cardiac computed tomography angiography (CCTA) is precise in noninvasive coronary atherosclerosis characterization but its value in the diagnosis of intracoronary thrombus remains unknown. Therefore, our aim was to evaluate CCTA for intracoronary thrombus and stenosis detection in patients with acute coronary syndromes with high thrombus burden selected for a deferred stenting strategy. METHODS: We systematically performed a CCTA in consecutive patients following a deferred stenting strategy, 24 h before the scheduled repeated coronary angiography including optical coherence tomography (OCT) imaging. Intracoronary thrombus and residual stenosis were blindly and independently evaluated by both techniques. Agreement was determined per lesion using the weighted Kappa ( K ) coefficient and absolute intraclass correlation coefficient (ICC). A stratified analysis according to OCT-detected thrombus burden was also performed. RESULTS: Thirty lesions in 28 consecutive patients were analyzed. Concordance between CCTA and repeated coronary angiography in thrombus detection was good ( K = 0.554; P < 0.001), but both showed poor agreement with OCT. CCTA needed >11.5% thrombus burden on OCT to obtain adequate diagnostic accuracy. The lesions detected by angiography were more frequently classified as red thrombus (76.5 vs. 33.3%; P = 0.087) on OCT. CCTA showed an excellent concordance with coronary angiography in diameter measurement (ICC = 0.85; P < 0.001) and was able to identify all the patients with severe residual stenosis. CONCLUSIONS: Although CCTA showed just a good concordance with angiography in intracoronary thrombus detection, the agreement in residual stenosis was excellent. Thus, in patients with a high-thrombus burden selected for a deferred stenting strategy CCTA may substitute repeat angiography.

Correlation between fractional flow reserve and instantaneous wave-free ratio with morphometric assessment by optical coherence tomography in diabetic patients.

Currently there is lack of data regarding the use of optical coherence tomography (OCT) to depict the hemodynamic relevance of coronary stenoses in diabetic patients. We sought to assess the diagnostic accuracy of OCT-derived morphologic assessment in identifying hemodynamically significant coronary lesions as determined by both, the resting instantaneous wave-free ratio (iFR) and the hyperemic fractional flow reserve (FFR) in diabetic patients. Diabetic patients presenting with at least one intermediate coronary lesion were prospectively and consecutively enrolled. All lesions were systematically assessed by iFR, FFR and OCT. A total of 41 intermediate lesions were analysed. Mean iFR and FFR values were 0.90 ± 0.04 and 0.81 ± 0.06, respectively (intra-class correlation coefficient 0.49; 95% CI 0.22-0.79). A moderate correlation between iFR and OCT derived minimal lumen diameter (MLD, r = 0.49) and minimal lumen area (MLA, r = 0.50) was found. Conversely, there was a poor correlation between FFR and OCT-derived MLD (r = 0.34) and MLA (r = 0.32). The diagnostic efficiency of MLA and MLD to identify iFR significant stenoses showed an AUC of 0.82 (95% CI 0.69-0.95) for MLD and 0.83 (95% CI 0.71-0.96) for MLA. A worse diagnostic efficiency was found when FFR was used as the reference with an AUC of 0.71 (95% CI 0.54-0.87) for MLD and 0.70 (95% CI 0.53-0.87). OCT-derived MLA and MLD were the strongest independent anatomic predictors of abnormal iFR and FFR values. In diabetic patients, OCT-derived MLA and MLD showed a moderate diagnostic efficiency in identifying functionally significant coronary stenoses by FFR or iFR. In diabetics, anatomic OCT measurements better predicted resting than FFR-determined physiologically significant lesions.

Diagnostic accuracy of a hybrid approach of instantaneous wave-free ratio and fractional flow reserve using high-dose intracoronary adenosine to characterize intermediate coronary lesions: Results of the PALS (Practical Assessment of Lesion Severity) prospective study.

OBJECTIVES: We sought to investigate the diagnostic accuracy of instantaneous wave-free ratio (iFR) and high-dose intracoronary adenosine fractional flow reserve (IC-FFR) compared with classical intravenous adenosine fractional flow reserve (IV-FFR) to assess coronary stenosis severity. The usefulness of two hybrid strategies combining iFR and high-dose IC-FFR was also evaluated. BACKGROUND: Physiological assessment of intermediate coronary stenoses to guide revascularization is currently recommended. METHODS: Consecutive real-world patients with angiographically intermediate coronary stenosis (40-80% diameter stenosis) were prospectively included in the PALS (Practical Assessment of Lesion Severity) study. In every target lesion iFR, high-dose IC-FFR and IV-FFR were systematically measured to assess the accuracy of an hybrid sequential approach combining iFR and IC-FFR. RESULTS: A total of 106 patients with 121 intermediate coronary lesions were analyzed. Both, iFR and IC-FFR showed a significant correlation with IV-FFR (iFR: r = 0.60, 95%CI 0.48-0.70; IC-FFR: r = 0.88; 95%CI: 0.83-0.92). High-dose IC-FFR provided lower FFR values than IV-FFR (0.81 ± 0.08 vs. 0.82 ± 0.09, P = 0.25). Using a receiver-operating-characteristic curve an optimal iFR threshold of 0.91 for the screening test was identified. A sequential test strategy (initial iFR followed by IC-FFR only in lesions with iFR <0.91) yielded an excellent diagnostic accuracy (96.7%, 95%CI 96.7-99.1%) with a sensitivity, specificity, positive and negative predicted values of 100%, 94.7%, 91.8%, and 100%, respectively. A hybrid approach using the previously described iFR gray zone (0.85-0.94) also provided an excellent diagnostic accuracy (95%, 95%CI: 89.5-98.1%). CONCLUSIONS: In patients with intermediate coronary lesions a hybrid strategy by using a sequential approach of iFR and high-dose IC-FFR, provided a very good diagnostic performance to identify physiologically significant stenoses. © 2017 Wiley Periodicals, Inc.

Reliability of physiological assessment of coronary stenosis severity using intracoronary pressure techniques: a comprehensive analysis from a large cohort of consecutive intermediate coronary lesions.

AIMS: We sought to assess the reliability of the most frequently used intracoronary physiologic indices (including intravenous adenosine FFR [IV-FFR], intracoronary low-dose adenosine FFR [LD-IC-FFR], intracoronary high-dose adenosine FFR [HD-IC-FFR], Pd/Pa and iFR). We also sought to analyse factors affecting their reproducibility in a real-world patient population. METHODS AND RESULTS: A total of 91 lesions in 86 consecutive patients were included. Measurements of all physiological indices were repeated within a systematic standardised prospective protocol. All measured indices showed excellent test-retest reliability, with intraclass correlation coefficient (ICC) over 0.96. IV-FFR showed the highest coefficient of variation (CV) values among the studied measurements (Pd/Pa: 0.05; iFR: 0.10; LD-IC-FFR: 0.10; HD-IC-FFR: 0.08; IV-FFR: 0.12). Pd/Pa was significantly less variable than the other indices. On multivariate analysis, female gender, distal lesion location, history of hypertension or kidney failure, as well as presentation as an acute coronary syndrome, were associated with more variability in all physiological intracoronary measurements. CONCLUSIONS: The reliability of most frequently used intracoronary physiologic indices is high. Clinical and anatomic factors significantly influence the reliability of these physiologic indices.