The pressure-derived microvascular resistance reserve and its correlation to Doppler MRR measurement-a proof of concept study.

Background: Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure. Purpose: We aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique. Methods: Hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRRp-3D). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRRp-3D. Results: In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpbmax and MRRp-3D (r 2 = 0.74, p < 0.0001). Using this relation (MRRp-3D = 1.04 + 0.51 × MRRpbmax), the linear prediction of the MRR was tested in the validation cohort of 19 measurements against the gold standard Doppler wire technique. A significant correlation was found between the linearly predicted and the measured values (r = 0.54, p = 0.01). If the area stenosis (AS%) was included to a quadratic prediction model, the correlation was improved (r = 0.63, p = 0.004). Conclusions: The MRR can be predicted reliably to assess microvascular function by our simple model. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement provides a simultaneous physiological assessment of the macro- and microvasculature.

Angiography-based coronary microvascular assessment with and without intracoronary pressure measurements: a systematic review.

BACKGROUND: In recent years, several indices have been proposed for quantifying coronary microvascular resistance. We intended to conduct a comprehensive review that systematically evaluates indices of microvascular resistance derived from angiography. OBJECTIVE: The objective of this study was to identify and analyze angiography-derived indices of microvascular resistance that have been validated against an invasive reference method. We aimed to compare their limits of agreement with their reference methods and explore their advantages and inherent limitations. METHODS AND RESULTS: We searched PubMed from inception until 2022 for studies on different techniques for quantifying microvascular resistance. Seven studies met the inclusion criteria. Five studies included techniques that applied calculations based solely on invasive angiography, and were validated against invasively measured thermodilution-derived index of microvascular resistance. The remaining two studies combined angiography with invasively measured intracoronary pressure data, and were validated against invasive Doppler measurements. We converted the ± 1.96 standard deviation limits of agreement with the reference method from the seven studies into percentages relative to the cut-off value of the reference method. The lower limits of agreement for angiography-based methods ranged from - 122 to - 60%, while the upper limits ranged from 74 to 135%. The range of the limits of agreement was considerably lower for the two combined angiography- and pressure-based methods, standing at - 52 to 60% and - 25 to 27%. CONCLUSION: Our findings suggest that combined angiography- and pressure-based methods provide a more reliable assessment of microvascular resistance compared to methods relying solely on angiography. Central illustration. Comparative assessment of image-based methods quantifying microvascular resistance with and without intracoronary pressure measurements. Angiography-based methods rely on angiography alone to calculate the microvascular resistance by utilizing angiographic frame counting to extrapolate coronary flow (Q) and subsequently deriving distal coronary pressure using fluid dynamic equations. Combined angiography- and pressure-based methods utilize invasive intracoronary pressure gradients measured during rest and maximal vasodilation to determine coronary flow in their calculation of microvascular resistance. The combined methods showed more acceptable levels of agreement with their reference methods compared to angiography-based methods alone.

Novel Method to Detect Pitfalls of Intracoronary Pressure Measurements by Pressure Waveform Analysis.

Potential pitfalls of fractional flow reserve (FFR) measurements are well-known drawbacks of invasive physiology measurement, e.g., significant drift of the distal pressure trace may lead to the misclassification of stenoses. Thus, a simultaneous waveform analysis of the pressure traces may be of help in the quality control of these measurements by online detection of such artefacts as the drift or the wedging of the catheter. In the current study, we analysed the intracoronary pressure waveform with a dedicated program. In 130 patients, 232 FFR measurements were performed and derivative pressure curves were calculated. Local amplitude around the dicrotic notch was calculated from the distal intracoronary pressure traces (δdPn/dt). A unidimensional arterial network model of blood flow was employed to simulate the intracoronary pressure traces at different flow rates. There was a strong correlation between δdPn/dt values measured during hyperaemia and FFR (r = 0.88). Diagnostic performance of distal δdPn/dt ≤ 3.52 for the prediction of FFR ≤ 0.80 was 91%. The correlation between the pressure gradient and the corresponding δdPn/dt values obtained from all measurements independently of the physiological phase was also significant (r = 0.80). During simulation, the effect of flow rate on δdPn/dt further supported the close correlation between the pressure ratios and δdPn/dt. Discordance between the FFR and the δdPn/dt can be used as an indicator of possible technical problems of FFR measurements. Hence, an online calculation of the δdPn/dt may be helpful in avoiding some pitfalls of FFR evaluation.

Pressure- and 3D-Derived Coronary Flow Reserve with Hydrostatic Pressure Correction: Comparison with Intracoronary Doppler Measurements.

Purpose: To develop a method of coronary flow reserve (CFR) calculation derived from three-dimensional (3D) coronary angiographic parameters and intracoronary pressure data during fractional flow reserve (FFR) measurement. Methods: Altogether 19 coronary arteries of 16 native and 3 stented vessels were reconstructed in 3D. The measured distal intracoronary pressures were corrected to the hydrostatic pressure based on the height differences between the levels of the vessel orifice and the sensor position. Classical fluid dynamic equations were applied to calculate the flow during the resting state and vasodilatation based on morphological data and intracoronary pressure values. 3D-derived coronary flow reserve (CFRp-3D) was defined as the ratio between the calculated hyperemic and the resting flow and was compared to the CFR values simultaneously measured by the Doppler sensor (CFRDoppler). Results: Haemodynamic calculations using the distal coronary pressures corrected for hydrostatic pressures showed a strong correlation between the individual CFRp-3D values and the CFRDoppler measurements (r = 0.89, p < 0.0001). Hydrostatic pressure correction increased the specificity of the method from 46.1% to 92.3% for predicting an abnormal CFRDoppler < 2. Conclusions: CFRp-3D calculation with hydrostatic pressure correction during FFR measurement facilitates a comprehensive hemodynamic assessment, supporting the complex evaluation of macro-and microvascular coronary artery disease.

Anatomical Assessment vs. Pullback REsting full-cycle rAtio (RFR) Measurement for Evaluation of Focal and Diffuse CoronarY Disease: Rationale and Design of the "READY Register".

Background: The morphology and functional severity of coronary stenosis show poor correlation. However, in clinical practice, the visual assessment of the invasive coronary angiography is still the most common means for evaluating coronary disease. The fractional flow reserve (FFR), the coronary flow reserve (CFR), and the resting full-cycle ratio (RFR) are established indices to determine the hemodynamic significance of a coronary stenosis. Design/Methods: The READY register (NCT04857762) is a prospective, multicentre register of patients who underwent invasive intracoronary FFR and RFR measurement. The main aim of the registry is to compare the visual estimate of coronary lesions and the functional severity of the stenosis assessed by FFR, as well as the RFR pullback. Characterizations of the coronary vessel for predominantly focal, diffuse, or mixed type disease according to visual vs. RFR pullback determination will be compared. The secondary endpoint of the study is a composite of major adverse cardiac events, including death, myocardial infarction, and repeat coronary revascularization at 1 year. These endpoints will be compared in patients with non-ischemic FFR in the subgroup of cases where the local pressure drop indicates a focal lesion according to the definition of ΔRFR > 0.05 (for <25 mm segment length) and in the subgroup without significant ΔRFR. In case of an FFR value above 0.80, an extended physiological analysis is planned to diagnose or exclude microvascular disease using the CFR/FFR index. This includes novel flow dynamic modeling for CFR calculation (CFRp-3D). Conclusion: The READY register will define the effect of RFR measurement on visual estimation-based clinical decision-making. It can identify a prognostic value of ΔRFR during RFR pullback, and it would also explore the frequency of microvascular disease in the patient population with FFR > 0.80. Clinical Trial Registration: ClinicalTrials.gov (NCT04857762).

The Holistic Coronary Physiology Display: Calculation of the Flow Separation Index in Vessel-Specific Individual Flow Range during Fractional Flow Reserve Measurement Using 3D Coronary Reconstruction.

In order to make optimal decisions on the treatment of atherosclerotic coronary heart disease (CHD), appropriate evaluation is necessary, including both the anatomical and physiological assessment of the coronary arteries. According to current guidelines, a fractional flow reserve (FFR)-based clinical decision is recommended, but coronary flow reserve (CFR) measurements and microvascular evaluation should also be considered in special cases for a detailed exploration of the coronary disease state. We aimed to generate an extended physiological evaluation during routine FFR measurement and define a new pathological flow-related prognostic factor. Fluid dynamic equations were applied to calculate CFR on the basis of the three-dimensional (3D) reconstruction of the invasively acquired coronary angiogram and the measured intracoronary pressure data. A new, potentially robust prognostic parameter of a coronary lesion called the "flow separation index" (FSi), which is thought to detect the pathological flow amount through a stenosis was introduced in a vessel-specific flow range. Correlations between FSi and the clinically established physiological indices (CFR and FFR) were determined. The FSi was calculated in 19 vessels of 16 patients, including data from the pre- and post-stent revascularization treatment of 3 patients. There was no significant correlation between the FSi and the CFR (r = -0.23, p = 0.34); however, there was significant negative correlation between the FSi and the FFR (r = -0.66, p = 0.002). An even stronger correlation was found between the FSi and the ratio of the resting pressure ratio and the FFR (r = 0.92, p < 0.0001). The diagnostic power of the FSi for predicting the FFR value of <0.80, as a gold standard prognostic factor, was tested by receiver operating characteristic analysis. FSi > 0.022 proved to be the cutoff value of the prediction of a pathologically low FFR with a 0.856 area under the curve (95% confidence interval: 0.620 to 0.972). The present flow-pressure-velocity display provides a comprehensive summary of patient-specific pathophysiology in CHD. The consequences of epicardial stenoses can be evaluated together with their complex relations to microvascular conditions. Based on these values, clinical decision-making concerning both pharmacological therapy and percutaneous or surgical revascularization may be more precisely guided.

Predictors of Hospital Mortality in Patients with Acute Coronary Syndrome Complicated by Cardiogenic Shock.

As demonstrated by earlier studies, pre-hospital triage with trans-telephonic electrocardiogram (TTECG) and direct referral for catheter therapy shows great value in the management of out-of-hospital chest pain emergencies. It does not only improve in-hospital mortality in ST-segment elevation myocardial infarction, but it has also been identified as an independent predictor of higher in-hospital survival rate. Since TTECG-facilitated triage shortens both transport time and percutaneous coronary intervention (PCI)-related procedural time intervals, it was hypothesized that even high-risk patients with acute coronary syndrome (ACS) and cardiogenic shock (CS) might also benefit from TTECG-based triage. Here, we decided to examine our database for new triage- and left ventricular (LV) function-related parameters that can influence in-hospital mortality in ACS complicated by CS. ACS patients were divided into two groups, namely, (1) hospital death patients (n = 77), and (2) hospital survivors (control, n = 210). Interestingly, TTECG-based consultation and triage of CS and ACS patients were confirmed as significant independent predictors of lower hospital mortality risk (odds ratio (OR) 0.40, confidence interval (CI) 0.21-0.76, p = 0.0049). Regarding LV function and blood chemistry, a good myocardial reperfusion after PCI (high area at risk (AAR) blush score/AAR LV segment number; OR 0.85, CI 0.78-0.98, p = 0.0178) and high glomerular filtration rate (GFR) value at the time of hospital admission (OR 0.97, CI 0.96-0.99, p = 0.0042) were the most crucial independent predictors of a decreased risk of in-hospital mortality in this model. At the same time, a prolonged time interval between symptom onset and hospital admission, successful resuscitation, and higher peak creatine kinase activity were the most important independent predictors for an increased risk of in-hospital mortality. In ACS patients with CS, (1) an early TTECG-based teleconsultation and triage, as well as (2) good myocardial perfusion after PCI and a high GFR value at the time of hospital admission, appear as major independent predictors of a lower in-hospital mortality rate.