Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

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BACKGROUND: In 5%-25% of non-ST-elevation acute coronary syndrome (NSTE-ACS) patients, coronary angiography reveals no obstructive coronary arteries (MINOCA). Coronary microvascular disease (CMD) is a potential causal pathophysiological mechanism in these patients and can be diagnosed by continuous thermodilution assessment. Recently, the microvascular resistance reserve (MRR) has been introduced as a novel index to assess the vasodilatory capacity of the microcirculation. However, continuous thermodilution and MRR have never been investigated in the acute setting in MINOCA patients and invasive assessment of the microcirculation in these patients are currently lacking.
OBJECTIVE: The objectives of the study were to investigate the incidence of CMD (MRR ≤ 2.7) in patients with MINOCA and to evaluate the feasibility and safety of continuous thermodilution-based assessment during index coronary angiography in the acute setting.
METHODS: This study was a prospective, observational, pilot study investigating coronary physiology in the acute setting in MINOCA patients. Patients admitted with a diagnosis of NSTE-ACS were eligible for inclusion.
RESULTS: In total, 19 MINOCA patients were included in this analysis; the mean age was 70 ± 9 years, and 79% were females. CMD was present in 6 patients (32%). Qrest was significantly higher in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (0.076 [0.057-0.100] vs. 0.049 [0.044-0.071] L/min, p = 0.03). Rµ,rest was significantly lower in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (1083 [710-1510] vs. 1563 [1298-1970] WU, p = 0.04). No periprocedural complications or hemodynamic instability have occurred during continuous thermodilution assessment during the index coronary angiography.
CONCLUSIONS: In patients admitted for MINOCA undergoing immediate coronary angiography, continuous thermodilution assessment and MRR are feasible and safe in the acute setting, and evidence of functional CMD could be observed in one-third of the MINOCA patients.

Computer simulations of coronary fractional flow reserve (FFR) based on coronary imaging have emerged as an attractive alternative to invasive measurements. However, most methods are proprietary and employ non-physiological assumptions. Our aims were to develop and validate a physiologically realistic open-source simulation model for coronary flow, and to use this model to predict FFR based on intracoronary optical coherence tomography (OCT) data in individual patients. We included patients undergoing elective coronary angiography with angiographic borderline coronary stenosis. Invasive measurements of coronary hyperemic pressure and absolute flow and OCT imaging were performed. A computer model of coronary flow incorporating pulsatile flow and the effect of left ventricular contraction was developed and calibrated, and patient-specific flow simulation was performed. Forty-eight coronary arteries from 41 patients were included in the analysis. Average FFR was 0.79 ± 0.14, and 50% had FFR ≤ 0.80. Correlation between simulated and measured FFR was high (r = 0.83, p < 0.001). Average difference between simulated FFR and observed FFR in individual patients was - 0.009 ± 0.076. Overall diagnostic accuracy for simulated FFR ≤ 0.80 in predicting observed FFR ≤ 0.80 was 0.88 (0.75-0.95) with sensitivity 0.79 (0.58-0.93) and specificity 0.96 (0.79-1.00). The positive predictive value was 0.95 (0.75-1.00) and the negative predictive value was 0.82 (0.63-0.94). In conclusion, realistic simulations of whole-cycle coronary flow can be produced based on intracoronary OCT data with a new, computationally simple simulation model. Simulated FFR had moderate numerical agreement with observed FFR and a good diagnostic accuracy for predicting hemodynamic significance of coronary stenoses.

BACKGROUND: Despite the recommendation of coronary physiology to guide revascularization in angiographically intermediate stenoses without established correlation to ischemia, its uptake in clinical practice is slow.
OBJECTIVE: This study aimed to analyze the use of coronary physiology in clinical practice.
METHODS: Based on a multicenter registry (Fractional Flow Reserve Fax Registry, F(FR)2, ClinicalTrials.gov identifier NCT03055910), clinical use, consequences, and complications of coronary physiology were systematically analyzed.
RESULTS: F(FR)2 enrolled 2,000 patients with 3,378 intracoronary pressure measurements. Most measurements (96.8%) were performed in angiographically intermediate stenoses. Out of 3,238 lesions in which coronary physiology was used to guide revascularization, revascularization was deferred in 2,643 (78.2%) cases. Fractional flow reserve (FFR) was the most common pressure index used (87.6%), with hyperemia induced by an intracoronary bolus of adenosine in 2,556 lesions (86.4%) and intravenous adenosine used for 384 measurements (13.0%). The route of adenosine administration did not influence FFR results (change-in-estimate -3.1% for regression model predicting FFR from diameter stenosis). Agreement with the subsequent revascularization decision was 93.4% for intravenous and 95.0% for intracoronary adenosine (p = 0.261). Coronary artery occlusion caused by the pressure wire was reported in two cases (0.1%) and dissection in three cases (0.2%), which was fatal once (0.1%).
CONCLUSIONS: In clinical practice, intracoronary pressure measurements are mostly used to guide revascularization decisions in angiographically intermediate stenoses. Intracoronary and intravenous administration of adenosine seem equally suited. While the rate of serious complications of wire-based intracoronary pressure measurements in clinical practice seems to be low, it is not negligible.

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Despite guideline-based recommendation of the interchangeable use of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) to guide revascularization decision-making, iFR/FFR could demonstrate different physiological or clinical outcomes in some specific patient or lesion subsets. Therefore, we sought to investigate the impact of difference between iFR and FFR-guided revascularization decision-making on clinical outcomes in patients with left main disease (LMD). In this international multicenter registry of LMD with physiological interrogation, we identified 275 patients in whom physiological assessment was performed with both iFR/FFR. Major adverse cardiovascular event (MACE) was defined as a composite of death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The receiver-operating characteristic analysis was performed for both iFR/FFR to predict MACE in respective patients in whom revascularization was deferred and performed. In 153 patients of revascularization deferral, MACE occurred in 17.0% patients. The optimal cut-off values of iFR and FFR to predict MACE were 0.88 (specificity:0.74; sensitivity:0.65) and 0.76 (specificity:0.81; sensitivity:0.46), respectively. The area under the curve (AUC) was significantly higher for iFR than FFR (0.74; 95%CI 0.62-0.85 vs. 0.62; 95%CI 0.48-0.75; p = 0.012). In 122 patients of coronary revascularization, MACE occurred in 13.1% patients. The optimal cut-off values of iFR and FFR were 0.92 (specificity:0.93; sensitivity:0.25) and 0.81 (specificity:0.047; sensitivity:1.00), respectively. The AUCs were not significantly different between iFR and FFR (0.57; 95%CI 0.40-0.73 vs. 0.46; 95%CI 0.31-0.61; p = 0.43). While neither baseline iFR nor FFR was predictive of MACE in patients in whom revascularization was performed, iFR-guided deferral seemed to be safer than FFR-guided deferral.

BACKGROUND: Prognostic value of poststenting fractional flow reserve (FFR) remains uncertain in patients undergoing an imaging-guided optimal stenting strategy.
OBJECTIVE: The authors evaluated the prognostic value of poststenting FFR according to the intracoronary imaging-guided lesion preparation, stent sizing, and postdilation (iPSP) strategy to optimize stent outcomes.
METHODS: Poststenting FFR assessment was performed in 1,108 lesions in 1,005 patients from the IRIS-FFR registry. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 5 years.
RESULTS: At the index procedure, 326 lesions (29.4%) were treated using all 3 parts of the iPSP strategy. In the overall population, poststenting FFR was significantly associated with the risk of TVF at 5 years (per 0.01 increase of FFR, adjusted HR [aHR]: 0.94; 95% CI: 0.90-0.98; P = 0.004). Significant interaction was detected between poststenting FFR and the iPSP strategy on the risk of TVF at 5 years (P = 0.045 for interaction). In the iPSP group, poststenting FFR was not associated with the risk of TVF at 5 years (per 0.01 increase of FFR, aHR: 1.00; 95% CI: 0.96-1.05; P = 0.95), whereas a significant association between poststenting FFR and TVF at 5 years was observed in the no iPSP group (per 0.01 increase of FFR, aHR: 0.94; 95% CI: 0.90-0.99; P = 0.009).
CONCLUSIONS: Poststenting FFR showed a significant association with cardiac events. However, its prognostic value appeared to be limited after the application of an imaging-guided optimal stenting strategy.

BACKGROUND: Fluid-filled pressure guidewires are unaffected by the previously inevitable hydrostatic pressure gradient (HPG). This study aimed to compare simultaneous pressure measurements with fluid-filled and sensor-tipped pressure guidewires.
METHODS: Fifty patients underwent fractional flow reserve (FFR) and Pd/Pa measurement with a fluid-filled and a sensor-tipped pressure guidewire simultaneously. To assess maneuverability, patients were randomized with respect to which pressure guidewire was used to cross the lesion first. Lateral fluoroscopy was used to estimate height difference between catheter tip and distal wire position (and thus HPG). Agreement between pressure measurements was studied.
RESULTS: Measurements were performed in LM (4% (n = 2)), LAD (44% (n = 22)), LCX (26% (n = 13)), and RCA (26% (n = 13)). Simultaneous pressure measurements showed excellent agreement (mean FFR difference - 0.01 ± 0.03 (r = 0.959, p < 0.001), mean Pd/Pa difference - 0.01 ± 0.04 (r = 0.929, p < 0.001)). FFR was ≤0.80 in 42.6% (n = 20) with fluid-filled FFR measurements versus 46.8% (n = 22) by sensor-tipped FFR measurements. Mean height difference was 15 ± 34 mm, and strongly dependent on the coronary artery (LAD 45 ± 10 mm, LCX -23 ± 16 mm, RCA -13 ± 17 mm). There was a strong correlation between height difference and difference in pressure ratios between sensor-tipped and fluid-filled pressure guidewires (FFR r = -0.850, p < 0.001; Pd/Par = -0.641, p < 0.001). Largest FFR differences were present in the LAD (-0.04 ± 0.02). After HPG correction, mean difference between HPG-corrected sensor-tipped FFR and fluid-filled FFR was 0.00 ± 0.02, mean Pd/Pa difference was 0.01 ± 0.03.
CONCLUSIONS: This study shows excellent overall correlation between FFR and Pd/Pa measurements with both pressure guidewires. Differences measured with fluid-filled and sensor-tipped pressure guidewires are vessel-specific and attributable to hydrostatic pressure gradients (NCT04802681).

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