451 Deferral of coronary revascularization in patients with reduced ejection fraction based on physiological assessment: impact on long-term survival

Aims Deferring percutaneous coronary intervention (PCI) in patients with non-significant stenoses based on fractional flow reserve (FFR) is associated with favourable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction (LVEF) is unclear. To investigate whether FFR provides adjunctive clinical benefit compared to coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced LVEF. Methods and results Consecutive patients (n = 4577) with reduced LVEF (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We eventually included patients with at least one intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR-guided) or angiography alone (angiography-guided). The primary endpoint of the study was the cumulative incidence of all-cause death at 10 years. The secondary endpoint [the incidence of major adverse cardiovascular and cerebrovascular events (MACCE)], was a composite of all-cause death, myocardial infarction, any revascularization and stroke. A total of 840 patients were included (206 in the FFR-guided and 634 in the angiography-guided group). Median clinical follow-up was 7 years [IQR: (3.22–11.08)]. After 1:1 propensity score matching, baseline characteristics between the two groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group [94 (45.6%) vs. 119 (57.8%), HR: 0.65 (95% CI: 0.49–0.85), P < 0.01]. The rate of major adverse cardiovascular and cerebrovascular events [(MACCE), a composite of all-cause death, myocardial infarction, any revascularization, and stroke) was lower in the FFR-guided group [123 (59.7%) vs. 139 (67.5%), HR: 0.75 (95% CI: 0.59–0.95), P = 0.02]. Conclusions In patients with reduced LVEF, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and MACCE at 10 years.

Importance of Visual Estimation of Coronary Artery Stenoses and Use of Functional Evaluation for Appropriate Guidance of Coronary Revascularization—Multiple Operator Evaluation

Background: Visual estimation (VE) of coronary stenoses is the first step during invasive coronary angiography. The aim of this study was to evaluate the accuracy of VE together with invasive functional assessment (IFA) in defining the functional significance (FS) of coronary stenoses based on the opinion of multiple operators. Methods: Fourteen independent operators visually evaluated 133 coronary lesions which had a previous FFR measurement, indicating the degree of stenosis (DS), FS and IFA intention. We determined the accuracy of FS prediction using several scenarios combining individual and group decision, considering IFA as deemed necessary by the operator or only in intermediate lesions. Results: The accuracy of VE in predicting FS was largely variable between operators (average 66.1%); it improved significantly when IFA was used either as per operator’s opinion (86.3%; p < 0.0001) or only in intermediate DS (82.9; p < 0.0001). There was no significant difference between using IFA per observer’s opinion or only in intermediate DS lesions (p = 0.166). The poorest accuracy of VE for FS was obtained in intermediate DS lesions (59.1%). Conclusions: There are significant inter-observer differences in reporting the degree of DS, while the accuracy of VE prediction of FS is also largely dependent on the operator, and the worst performance is obtained in the evaluation of intermediate DS.

Quantitative Flow Ratio Is Associated with Extent and Severity of Ischemia in Non-Culprit Lesions of Patients with Myocardial Infarction

Quantitative flow ratio (QFR) is a novel method to assess the relevance of coronary stenoses based only on angiographic projections. We could previously show that QFR is able to predict the hemodynamic relevance of non-culprit lesions in patients with myocardial infarction. However, it is still unclear whether QFR is also associated with the extent and severity of ischemia, which can effectively be assessed with imaging modalities such as cardiac magnetic resonance (CMR). Thus, our aim was to evaluate the associations of QFR with both extent and severity of ischemia. We retrospectively determined QFR in 182 non-culprit coronary lesions from 145 patients with previous myocardial infarction, and compared it with parameters assessing extent and severity of myocardial ischemia in staged CMR. Whereas ischemic burden in lesions with QFR > 0.80 was low (1.3 ± 5.5% in lesions with QFR ≥ 0.90; 1.8 ± 7.3% in lesions with QFR 0.81–0.89), there was a significant increase in ischemic burden in lesions with QFR ≤ 0.80 (16.6 ± 15.6%; p < 0.001 for QFR ≥ 0.90 vs. QFR ≤ 0.80). These data could be confirmed by other parameters assessing extent of ischemia. In addition, QFR was also associated with severity of ischemia, assessed by the relative signal intensity of ischemic areas. Finally, QFR predicts a clinically relevant ischemic burden ≥ 10% with good diagnostic accuracy (AUC 0.779, 95%-CI: 0.666–0.892, p < 0.001). QFR may be a feasible tool to identify not only the presence, but also extent and severity of myocardial ischemia in non-culprit lesions of patients with myocardial infarction.

Evaluation of the Safety and Efficacy of Coronary Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Stenoses: Evidence From the Serial Disrupt CAD Trials

Background: Previous understanding holds that rotational atherectomy and modified balloons remain the default strategy for severely calcified coronary stenoses. In recent years, coronary intravascular lithotripsy (IVL) provides new ideas. This study was conducted to evaluate the safety and efficacy of IVL for the treatment of severely calcified coronary stenoses.Methods: The serial Disrupt CAD trials (Disrupt CAD I, Disrupt CAD II, Disrupt CAD III, and Disrupt CAD IV) were included in this study. The safety endpoint was freedom from major adverse cardiovascular events (MACE) in hospital, at 30 days, and at 6 months following the index procedure. The efficacy endpoints included procedural success and angiographic success. Optical coherence tomography (OCT) was used to evaluate the mechanism of action of IVL quantifying the coronary artery calcification (CAC) characteristics and calcium plaque fracture.Results: We enrolled a total of 628 patients with a mean age of 71.8 years, 77.1% males. In these patients, the left anterior descending artery and right coronary artery were the most vulnerable vessels. The diameter stenosis was 64.6 ± 11.6% and the lesion length was 24.2 ± 11.4 mm. IVL had a favorable efficacy (93.0% procedural success, 97.5% angiographic success, and 100.0% stent delivery). Among the 628 patients, 568, 568, and 60 reported MACE endpoints in hospital, at 30 days, and at 6 months, respectively. The results showed that 528, 514, and 55 patients were free from MACE in hospital, at 30 days, and at 6 months, respectively. OCT measurements demonstrated that calcium fracture was the underlying mechanism of action for coronary IVL.Conclusions: IVL is safe and efficient for severely calcified coronary stenoses, and, importantly, calcium fracture facilitated increased vessel compliance and favorable stent expansion.

Agreement Between Invasive Wire-Based and Angiography-Based Vessel Fractional Flow Reserve Assessment on Intermediate Coronary Stenoses

Background: Angiography-based functional assessment of coronary stenoses emerges as a novel approach to assess coronary physiology. We sought to investigate the agreement between invasive coronary wire-based fractional flow reserve (FFR), resting full-cycle ratio (RFR), and angiography-based vessel FFR (vFFR) for the functional assessment of coronary stenoses in patients with coronary artery disease.Materials and Methods: Between Jan 01, 2018, and Dec 31, 2020, 298 patients with 385 intermediate lesions received invasive coronary wire-based functional assessment (FFR, RFR or both) at a single tertiary medical center. Coronary lesions involving ostium or left main artery were excluded. vFFR analysis was performed retrospectively based on aortic root pressure and two angiographic projections.Results: In total, 236 patients with 291 lesions were eligible for vFFR analysis. FFR and RFR were performed in 258 and 162 lesions, respectively. The mean FFR, RFR and vFFR value were 0.84 ± 0.08, 0.90 ± 0.09, and 0.83 ± 0.10. vFFR was significantly correlated with FFR (r = 0.708, P &lt; 0.001) and RFR (r = 0.673, P &lt; 0.001). The diagnostic performance of vFFR vs. FFR was accuracy 81.8%, sensitivity 77.4%, specificity 83.9%, positive predictive value 69.9%, and negative predictive value 88.5%. The discriminative power of vFFR for FFR ≤ 0.80 or RFR ≤ 0.89 was excellent. Area under the receiver operating characteristic curve (AUC) was 0.87 (95% CI:0.83–0.92) for FFR and 0.80 (95% CI:0.73–0.88) for RFR.Conclusion: Angiography-based vFFR has a substantial agreement with invasive wire-based FFR and RFR in patients with intermediate coronary stenoses. vFFR can be utilized to assess coronary physiology without a pressure wire in a post hoc manner.

OCT-Derived Plaque Morphology and FFR-Determined Hemodynamic Relevance in Intermediate Coronary Stenoses

Background: optical coherence tomography (OCT) might allow identifying lesion features reportedly associated with plaque vulnerability and increased risk of clinical events. Previous studies on correlation between OCT and functional lesion significance indices reported contradictory results, yet integration of complementary information from both modalities is gaining increased interest. The aim of the study was to compare plaque morphology using OCT in hemodynamically relevant vs. non-relevant lesions by fractional flow reserve (FFR). Methods: consecutive patients with intermediate grade coronary stenoses by angiography were evaluated by both FFR and OCT in this single-center study. Stenoses were labeled hemodynamically relevant in case of the FFR ≤ 0.80. Minimal lumen area (MLA), fibrous cap thickness (FCT), minimal cap thickness over the calcium, angle of the calcium, and necrotic core within the lesions were evaluated. Results: a total of 105 patients (124 vessels) were analyzed. Of them, 65 patients were identified with at least one lesion identified as hemodynamically relevant by FFR (72 vessels, 58.1%). Lesions with FFR ≤0.80 presented with lower mean and minimal lumen area (3.46 ± 1.29 vs. 4.65 ± 2.19, p =0.001 and 1.84 ± 0.97 vs. 2.66 ± 1.40, p = 0.001) compared to patients with FFR > 0.80. No differences were found between groups in the mean and minimal FCT, mean, and maximal necrotic core, calcium angle, as well as the overall rate of calcified and lipid plaques. Conclusion: hemodynamic relevance of intermediate grade lesions correlated moderately with the luminal assessment by OCT. No differences were identified in the plaque morphology between relevant and non-relevant coronary stenoses by FFR.

Modeling Left Ventricle Perfusion in Healthy and Stenotic Conditions

A theoretical fluid mechanical model is proposed for the investigation of myocardial perfusion in healthy and stenotic conditions. The model hinges on Terzaghi’s consolidation theory and reformulates the related unsteady flow equation for the simulation of the swelling–drainage alternation characterizing the diastolic–systolic phases. When compared with the outcome of experimental in vivo observations in terms of left ventricle transmural perfusion ratio (T.P.R.), the analytical solution provided by the present study for the time-dependent blood pressure and flow rate across the ventricle wall proves to consistently reproduce the basic mechanisms of both healthy and ischemic perfusion. Therefore, it could constitute a useful interpretative support to improve the comprehension of the basic hemodynamic mechanisms leading to the most common cardiac diseases. Additionally, it could represent the mathematical basis for the application of inverse methods aimed at estimating the characteristic parameters of ischemic perfusion (i.e., location and severity of coronary stenoses) via downstream ventricular measurements, possibly inspiring their assessment via non-invasive myocardial imaging techniques.