Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment.

BACKGROUND: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA). AIMS: This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. METHODS: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. RESULTS: On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest, LCAhyp, RCArest and RCAhyp, p<0.001 for between-vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom=1.55±0.35, RCAco-dom=1.40±0.27, RCAnon-dom=1.35; standard deviation not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases [97.9%] overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had a negligible impact on DSVR in both the RCA and LCA (DSVR x hyperaemic stenosis resistance R2 =0.018, p=0.03 and DSVR x coronary flow reserve R2 <0.001, p=0.98). CONCLUSIONS: In patients with coronary artery disease undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.

Respiration-related variations in Pd/Pa ratio and fractional flow reserve in resting conditions and during intravenous adenosine administration.

AIMS: We evaluated the occurrence and physiology of respiration-related beat-to-beat variations in resting Pd/Pa and FFR during intravenous adenosine administration, and its impact on clinical decision-making. METHODS AND RESULTS: Coronary pressure tracings in rest and at plateau hyperemia were analyzed in a total of 39 stenosis from 37 patients, and respiratory rate was calculated with ECG-derived respiration (EDR) in 26 stenoses from 26 patients. Beat-to-beat variations in FFR occurred in a cyclical fashion and were strongly correlated with respiratory rate (R2  = 0.757, p < 0.001). There was no correlation between respiratory rate and variations in resting Pd/Pa. When single-beat averages were used to calculate FFR, mean ΔFFR was 0.04 ± 0.02. With averaging of FFR over three or five cardiac cycles, mean ΔFFR decreased to 0.02 ± 0.02, and 0.01 ± 0.01, respectively. Using a FFR ≤ 0.80 threshold, stenosis classification changed in 20.5% (8/39), 12.8% (5/39) and 5.1% (2/39) for single-beat, three-beat and five-beat averaged FFR. The impact of respiration was more pronounced in patients with pulmonary disease (ΔFFR 0.05 ± 0.02 vs 0.03 ± 0.02, p = 0.021). CONCLUSION: Beat-to-beat variations in FFR during plateau hyperemia related to respiration are common, of clinically relevant magnitude, and frequently lead FFR to cross treatment thresholds. A five-beat averaged FFR, overcomes clinically relevant impact of FFR variation.

Time course of coronary flow capacity impairment in ST-segment elevation myocardial infarction.

BACKGROUND: Microvascular dysfunction in the setting of ST-elevated myocardial infarction (STEMI) plays an important role in long-term poor clinical outcome. Coronary flow reserve (CFR) is a well-established physiological parameter to interrogate the coronary microcirculation. Together with hyperaemic average peak flow velocity, CFR constitutes the coronary flow capacity (CFC), a validated risk stratification tool in ischaemic heart disease with significant prognostic value. This mechanistic study aims to elucidate the time course of the microcirculation as reflected by alterations in microcirculatory physiological parameters in the acute phase and during follow-up in STEMI patients. METHODS: We assessed CFR and CFC in the culprit and non-culprit vessel in consecutive STEMI patients at baseline (n = 98) and after one-week (n = 64) and six-month follow-up (n = 65). RESULTS: A significant trend for culprit CFC in infarct size as determined by peak troponin T (p = 0.004), time to reperfusion (p = 0.038), the incidence of final Thrombolysis In Myocardial Infarction 3 flow (p = 0.019) and systolic retrograde flow (p = 0.043) was observed. Non-culprit CFC linear contrast analysis revealed a significant trend in C-reactive protein (p = 0.027), peak troponin T (p < 0.001) and heart rate (p = 0.049). CFC improved both in the culprit and the non-culprit vessel at one-week (both p < 0.001) and six-month follow-up (p = 0.0013 and p < 0.001) compared with baseline. CONCLUSION: This study demonstrates the importance of microcirculatory disturbances in the setting of STEMI, which is relevant for the interpretation of intracoronary diagnostic techniques which are influenced by both culprit and non-culprit vascular territories. Assessment of non-culprit vessel CFC in the setting of STEMI might improve risk stratification of these patients following coronary reperfusion of the culprit vessel.

Time course of coronary flow capacity impairment in ST-segment elevation myocardial infarction.

BACKGROUND: Microvascular dysfunction in the setting of ST-elevated myocardial infarction (STEMI) plays an important role in long-term poor clinical outcome. Coronary flow reserve (CFR) is a well-established physiological parameter to interrogate the coronary microcirculation. Together with hyperaemic average peak flow velocity, CFR constitutes the coronary flow capacity (CFC), a validated risk stratification tool in ischaemic heart disease with significant prognostic value. This mechanistic study aims to elucidate the time course of the microcirculation as reflected by alterations in microcirculatory physiological parameters in the acute phase and during follow-up in STEMI patients. METHODS: We assessed CFR and CFC in the culprit and non-culprit vessel in consecutive STEMI patients at baseline (n = 98) and after one-week (n = 64) and six-month follow-up (n = 65). RESULTS: A significant trend for culprit CFC in infarct size as determined by peak troponin T (p = 0.004), time to reperfusion (p = 0.038), the incidence of final Thrombolysis In Myocardial Infarction 3 flow (p = 0.019) and systolic retrograde flow (p = 0.043) was observed. Non-culprit CFC linear contrast analysis revealed a significant trend in C-reactive protein (p = 0.027), peak troponin T (p < 0.001) and heart rate (p = 0.049). CFC improved both in the culprit and the non-culprit vessel at one-week (both p < 0.001) and six-month follow-up (p = 0.0013 and p < 0.001) compared with baseline. CONCLUSION: This study demonstrates the importance of microcirculatory disturbances in the setting of STEMI, which is relevant for the interpretation of intracoronary diagnostic techniques which are influenced by both culprit and non-culprit vascular territories. Assessment of non-culprit vessel CFC in the setting of STEMI might improve risk stratification of these patients following coronary reperfusion of the culprit vessel.

Artificial Intelligence for Aortic Pressure Waveform Analysis During Coronary Angiography: Machine Learning for Patient Safety.

OBJECTIVES: This study developed a neural network to perform automated pressure waveform analysis and allow real-time accurate identification of damping. BACKGROUND: Damping of aortic pressure during coronary angiography must be identified to avoid serious complications and make accurate coronary physiology measurements. There are currently no automated methods to do this, and so identification of damping requires constant monitoring, which is prone to human error. METHODS: The neural network was trained and tested versus core laboratory expert opinions derived from 2 separate datasets. A total of 5,709 aortic pressure waveforms of individual heart beats were extracted and classified. The study developed a recurrent convolutional neural network to classify beats as either normal, showing damping, or artifactual. Accuracies were reported using the opinions of 2 independent core laboratories. RESULTS: The neural network was 99.4% accurate (95% confidence interval: 98.8% to 99.6%) at classifying beats from the testing dataset when judged against the opinions of the internal core laboratory. It was 98.7% accurate (95% confidence interval: 98.0% to 99.2%) when judged against the opinions of an external core laboratory not involved in neural network training. The neural network was 100% sensitive, with no beats classified as damped misclassified, with a specificity of 99.8%. The positive predictive and negative predictive values were 98.1% and 99.5%. The 2 core laboratories agreed more closely with the neural network than with each other. CONCLUSIONS: Arterial waveform analysis using neural networks allows rapid and accurate identification of damping. This demonstrates how machine learning can assist with patient safety and the quality control of procedures.

Pressure-derived estimations of coronary flow reserve are inferior to flow-derived coronary flow reserve as diagnostic and risk stratification tools.

BACKGROUND: Pressure-derived coronary flow reserve (CFRpres) and pressure-bounded CFR (CFRpb) enable simple estimation of CFR from routine pressure measurements, but have been inadequately validated. We sought to compare CFRpres and CFRpb against flow-derived CFR (CFRflow) in terms of diagnostic accuracy, as well as regarding their comparative prognostic relevance. METHODS: We evaluated 453 intermediate coronary lesions with intracoronary pressure and flow measurements. CFR was defined as hyperemic flow/baseline flow. The lower bound (CFRpres) and upper bound of CFRpb were defined as √[(ΔPhyperemia) / (ΔPrest)] and [(ΔPhyperemia) / (ΔPrest)], respectively. Long-term follow-up (median: 11.8-years) was performed in 153 lesions deferred from treatment to document the occurrence of major adverse cardiac events (MACE) defined as a composite of cardiac death, myocardial infarction and target vessel revascularization. CFR < 2.0 was considered abnormal. RESULTS: CFRpb was normal or abnormal in 56.7% of stenoses, and indeterminate in 43.3% of stenoses. There was a poor diagnostic agreement between CFRpres and CFRpb with CFRflow (overall agreement: 45.5% and 71.6% of vessels, respectively). There was equivalent risk for long-term MACE for lesions with abnormal versus normal CFRpres (Breslow p = 0.562), whereas vessels with abnormal CFRflow were significantly associated with increased long-term MACE (Breslow p < 0.001). For vessels where CFRpb was abnormal or normal, there was equivalent risk for long-term MACE for vessels with abnormal versus normal CFRpb (Breslow p = 0.194), whereas vessels with abnormal CFRflow were associated with increased MACE rates over time (Breslow p < 0.001). CONCLUSIONS: Pressure-derived estimations of CFR poorly agree with flow-derived measurements of CFR, which may explain the inferior association with long-term MACE as compared to flow-derived CFR.

Microvascular dysfunction following ST-elevation myocardial infarction and its recovery over time.

AIMS: It is unclear whether microvascular dysfunction following ST-elevation myocardial infarction (STEMI) is prognostic for long-term left ventricular function (LVF), and whether recovery of the microvasculature status is associated with LVF improvement. The aim of this study was to assess whether microvascular dysfunction in the infarct-related artery (IRA), as assessed by coronary flow reserve (CFR) within one week after PPCI, was associated with LVF at both four months and two years. METHODS AND RESULTS: In 62 patients, CFR and hyperaemic microvascular resistance index (HMRI) in the IRA were assessed by intracoronary Doppler flow measurements within one week and at four months. CMR was performed at the same time points and also at two years. CFR at baseline was associated with left ventricular ejection fraction (LVEF) at four months (ß=4.66, SE=2.10; p=0.03) and at two-year follow-up (ß=5.84, SE=2.45; p=0.02). HMRI was not associated with LVF. In large infarcts, absolute improvement of CFR in the first four months was associated with LVEF improvement (ß=5.09, SE=1.86, p=0.01). CONCLUSIONS: Microvascular dysfunction, assessed by CFR, in the subacute phase of STEMI is prognostic for LVEF at four months and two years. This underlines the pivotal role of microvascular dysfunction following STEMI.

Invasive minimal Microvascular Resistance Is a New Index to Assess Microcirculatory Function Independent of Obstructive Coronary Artery Disease.

BACKGROUND: Coronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment of microcirculatory dysfunction by coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) is affected by coronary artery disease (CAD). In this study we propose minimal microvascular resistance (mMR) as a new measure of microcirculatory dysfunction and aim to determine whether mMR is influenced by CAD. METHODS AND RESULTS: We obtained 482 simultaneous measurements of intracoronary Doppler flow velocity and pressure. The mMR is defined as the ratio between distal coronary pressure and flow velocity during the hyperemic wave-free period. Measurements were divided into 2 cohorts. Cohort 1 was a paired analysis involving 81 pairs with a vessel with and without CAD to investigate whether HMR, CFR, and mMR are modulated by CAD. CFR was lower, and HMR was higher, in vessels with CAD than in vessels without CAD: 2.12±0.79 versus 2.56±0.63 mm Hg·cm-1·s, P<0.001, and 2.61±1.22 versus 2.31±0.89 mm Hg·cm-1·s, P=0.04, respectively. mMR was equal in vessels with and without CAD: 1.54±0.77 versus 1.53±0.57 mm Hg·cm-1·s, P=0.90. Differences for CFR occurred when FFR was 0.60 to 0.80 or ≤0.60 but not when FFR ≥0.80. For HMR, the difference occurred only when FFR ≤0.60. For mMR, no difference was observed in any FFR stratum. Cohort 2 was used for validation and showed significant relationships for CFR and HMR with FFR: Pearson r=0.488, P<0.001 and -0.159, P=0.03, respectively; mMR had no association with FFR: Pearson r=0.055; P=0.32. CONCLUSIONS: mMR is a novel index to assess microcirculatory dysfunction and is not modified by the presence of obstructive CAD.

Basal stenosis resistance index derived from simultaneous pressure and flow velocity measurements.

AIMS: Vasodilator-free basal stenosis resistance (BSR) equals fractional flow reserve (FFR) accuracy for ischaemia-inducing stenoses. Nonetheless, basal haemodynamic variability may impair BSR accuracy compared with hyperaemic stenosis resistance (HSR). We evaluated the influence of basal haemodynamic variability, as encountered in practice, on BSR accuracy versus HSR when derived from simultaneous pressure and flow velocity measurements, and determined its diagnostic performance for HSR-defined significant stenoses. METHODS AND RESULTS: Simultaneous coronary pressure and flow velocity were obtained in 131 stenoses. The impact of basal haemodynamic conditions on BSR was evaluated by means of their relationship with the relative difference between BSR and HSR. Diagnostic performance of BSR, FFR, iFR, and resting Pd/Pa was assessed by comparing the area under the curve (AUC), using HSR as reference standard. The relative difference between BSR and HSR was not associated with basal heart rate, aortic pressure or rate pressure product. Among all stenoses, as well as within the 0.6-0.9 FFR range, BSR AUC was significantly greater than resting Pd/Pa and iFR AUC; all other AUCs were equivalent. CONCLUSIONS: With simultaneous pressure and flow velocity measurements, basal conditions do not systematically limit BSR accuracy compared with HSR. Consequently, diagnostic performance of BSR is equivalent to FFR, and closely approximates HSR.

Coronary pressure and flow relationships in humans: phasic analysis of normal and pathological vessels and the implications for stenosis assessment: a report from the Iberian-Dutch-English (IDEAL) collaborators.

BACKGROUND: Our understanding of human coronary physiological behaviour is derived from animal models. We sought to describe physiological behaviour across a large collection of invasive pressure and flow velocity measurements, to provide a better understanding of the relationships between these physiological parameters and to evaluate the rationale for resting stenosis assessment. METHODS AND RESULTS: Five hundred and sixty-seven simultaneous intracoronary pressure and flow velocity assessments from 301 patients were analysed for coronary flow velocity, trans-stenotic pressure gradient (TG), and microvascular resistance (MVR). Measurements were made during baseline and hyperaemic conditions. The whole cardiac cycle and the diastolic wave-free period were assessed. Stenoses were assessed according to fractional flow reserve (FFR) and quantitative coronary angiography DS%. With progressive worsening of stenoses, from unobstructed angiographic normal vessels to those with FFR ≤ 0.50, hyperaemic flow falls significantly from 45 to 19 cm/s, Ptrend < 0.001 in a curvilinear pattern. Resting flow was unaffected by stenosis severity and was consistent across all strata of stenosis (Ptrend > 0.05 for all). Trans-stenotic pressure gradient rose with stenosis severity for both rest and hyperaemic measures (Ptrend < 0.001 for both). Microvascular resistance declines with stenosis severity under resting conditions (Ptrend < 0.001), but was unchanged at hyperaemia (2.3 ± 1.1 mmHg/cm/s; Ptrend = 0.19). CONCLUSIONS: With progressive stenosis severity, TG rises. However, while hyperaemic flow falls significantly, resting coronary flow is maintained by compensatory reduction of MVR, demonstrating coronary auto-regulation. These data support the translation of coronary physiological concepts derived from animals to patients with coronary artery disease and furthermore, suggest that resting pressure indices can be used to detect the haemodynamic significance of coronary artery stenoses.

Diagnostic and Prognostic Implications of Coronary Flow Capacity: A Comprehensive Cross-Modality Physiological Concept in Ischemic Heart Disease.

OBJECTIVES: The purpose of this study is to evaluate whether coronary flow capacity (CFC) improves discrimination of patients at risk for major adverse cardiac events (MACE) compared with coronary flow reserve (CFR) alone, and to study the diagnostic and prognostic implications of CFC in relation to contemporary diagnostic tests for ischemic heart disease (IHD), including fractional flow reserve (FFR). BACKGROUND: Although IHD results from a combination of focal obstructive, diffuse, and microcirculatory involvement of the coronary circulation, its diagnosis remains focused on focal obstructive causes. CFC comprehensively documents flow impairment in IHD, regardless of its origin, by interpreting CFR in relation to maximal flow (hyperemic average peak flow velocity [hAPV]), and overcomes the limitations of using CFR alone. This is governed by the understanding that ischemia occurs in vascular beds with substantially reduced hAPV and CFR, whereas ischemia is unlikely when hAPV or CFR is high. METHODS: Intracoronary pressure and flow were measured in 299 vessels (228 patients), where revascularization was deferred in 154. Vessels were stratified as having normal, mildly reduced, moderately reduced, or severely reduced CFC using CFR thresholds derived from published data and corresponding hAPV percentiles. The occurrence of MACE after deferral of revascularization was recorded during 11.9 years of follow-up (quartile 1: 10.0 years, quartile 3: 13.4 years). RESULTS: Combining CFR and hAPV improved the prediction of MACE over CFR alone (p = 0.01). After stratification in CFC, MACE rates throughout follow-up were strongly associated with advancing impairment of CFC (p = 0.002). After multivariate adjustment, mildly and moderately reduced CFC were associated with a 2.1-fold (95% confidence interval: 1.1 to 4.0; p = 0.017), and 7.1-fold (95% confidence interval: 2.9 to 17.1; p < 0.001) increase in MACE hazard, respectively, compared with normal CFC. Severely reduced CFC was identified by FFR ≤0.80 in 90% of cases, although ≥40% of vessels with normal or mildly reduced CFC still had an FFR ≤0.80. CONCLUSIONS: CFC provides a cross-modality platform for the diagnosis and risk-stratification of IHD and enriches the interpretation of contemporary diagnostic tests in IHD.

Combining Baseline Distal-to-Aortic Pressure Ratio and Fractional Flow Reserve in the Assessment of Coronary Stenosis Severity.

OBJECTIVES: This study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale. BACKGROUND: Pd/Pa is always available before FFR assessment, and emerging data supports the notion that baseline indices can determine the ischemic potential of coronary stenosis in selected subsets. METHODS: A total of 467 stenosed vessels from 363 patients were investigated with pressure and flow sensors during baseline and hyperemia: 168 vessels (135 patients) with thermodilution-derived flow, and 299 vessels (228 patients) with Doppler-derived flow. RESULTS: Pd/Pa correlated more strongly with CFR than FFR (ρ difference = 0.129; p for ρ comparison <0.001). Although Pd/Pa and FFR were closely correlated (ρ = 0.798; 95% confidence interval: 0.767 to 0.828), categorical discordance was observed in 19.3% of total vessels. Such discordance was associated with the patients' clinical profile and was characterized by contrastive changes in stenosis resistance, microcirculatory resistance, and the underlying CFR. Notably, all stenosis with Pd/Pa ≤0.83 (n = 74, 15.8%) progressed to FFR ≤0.80, and although no Pd/Pa cutoff was able to exclude the development of FFR ≤0.80 in the high end of values, only 15 (10.1%) vessels with Pd/Pa ≥0.96 (n = 149, 31.9%) developed FFR ≤0.80, from which none had definite ischemia, as defined by CFR ≤1.74. CONCLUSIONS: Combining baseline Pd/Pa with FFR seems to provide a more comprehensive physiological examination of stenosed coronary arteries and a closer pressure-based appraisal of the flow reserve of the downstream myocardial bed.

Change in coronary blood flow after percutaneous coronary intervention in relation to baseline lesion physiology: results of the JUSTIFY-PCI study.

BACKGROUND: Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters. METHODS AND RESULTS: Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s) and significantly less than hyperemic flow velocity (21.2±3 cm/s; P<0.01). The greatest increase in hyperemic flow velocity was observed when treating stenoses below physiological cut points; treating stenoses with fractional flow reserve ≤0.80 gained Δ28.5±3.8 cm/s, whereas those fractional flow reserve >0.80 had a significantly smaller gain (Δ4.6±2.3 cm/s; P<0.001). The change in pressure-only physiological indices demonstrated a curvilinear relationship to the change in hyperemic flow velocity but was flat for resting flow velocity. CONCLUSIONS: Pre-PCI physiology is strongly associated with post-PCI increase in hyperemic coronary flow velocity. Hyperemic flow velocity increases 6-fold more when stenoses classed as physiologically significant undergo PCI than when nonsignificant stenoses are treated. Resting flow velocity measured over the wave-free period changes at least 4-fold less than hyperemic flow velocity after PCI.

Head-to-head comparison of basal stenosis resistance index, instantaneous wave-free ratio, and fractional flow reserve: diagnostic accuracy for stenosis-specific myocardial ischaemia.

AIMS: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index. METHODS AND RESULTS: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC). Classification agreement with the reference standard was determined according to ROC curve-derived ischaemic cut-off values, as well as according to clinical cut-off values, equivalent to the 0.80 FFR cut-off. Across all stenoses, the discriminative value of BSR and FFR was equivalent (AUC: 0.90 and 0.91, respectively, p=0.46). In the iFR cohort, the discriminative value was equivalent for BSR, iFR, and FFR (AUC: 0.88, 0.84, and 0.88, respectively; p≥0.20 for all). At both ischaemic as well as clinical cut-off values, classification agreement with the reference standard was equivalent for BSR and FFR across all stenoses, as well as for BSR, iFR, and FFR in the iFR cohort. CONCLUSIONS: BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.

Primary PCI: time to change focus from epicardial reperfusion towards protection of the microvasculature.

Myocardial tissue perfusion remains compromised in 30-40% of patients with ST-segment elevation myocardial infarction (STEMI) despite restored epicardial patency after primary percutaneous coronary intervention (pPCI). This phenomenon is attributed to microvascular dysfunction secondary to numerous pathophysiological mechanisms, including distal embolisation of plaque and thrombus material. Its association with larger post-infarction myocardial necrosis, impaired left ventricular recovery, and worse clinical outcome illustrates the pertinence of a comprehensive armamentarium for the diagnosis, protection and treatment of microvascular dysfunction in STEMI patients. Current strategies to protect the microvasculature during pPCI are based on the assumption that distal embolisation of thrombotic and atheromatous debris is the main mechanism precipitating impaired myocardial tissue perfusion. However, recent findings suggest that this assumption is only true for the border zone of the ischaemic myocardium, whereas the infarct core consists of intramyocardial haemorrhage secondary to microvascular destruction, rather than obstruction. This observation has pertinent implications for contemporary and future adjuvant treatment strategies in STEMI patients. In this review, we provide an overview of the currently available armamentarium to assess the microvasculature, review contemporary strategies in pPCI to protect the myocardium, and discuss novel insights into microvascular pathophysiology that may help guide our focus from the coronary arteries to the microvasculature.

Baseline instantaneous wave-free ratio as a pressure-only estimation of underlying coronary flow reserve: results of the JUSTIFY-CFR Study (Joined Coronary Pressure and Flow Analysis to Determine Diagnostic Characteristics of Basal and Hyperemic Indices of Functional Lesion Severity-Coronary Flow Reserve).

BACKGROUND: Coronary flow reserve has extensive validation as a prognostic marker in coronary disease. Although pressure-only fractional flow reserve (FFR) improves outcomes compared with angiography when guiding percutaneous coronary intervention, it disagrees with coronary flow reserve classification 30% of the time. We evaluated whether baseline instantaneous wave-free ratio (iFR) could provide an improved pressure-only estimation of underlying coronary flow reserve. METHODS AND RESULTS: Invasive pressure and flow velocity were measured in 216 stenoses from 186 patients with coronary disease. The diagnostic relationship between pressure-only indices (iFR and FFR) and coronary flow velocity reserve (CFVR) was compared using correlation coefficient and the area under the receiver operating characteristic curve. iFR showed a stronger correlation with underlying CFVR (iFR-CFVR, ρ=0.68 versus FFR-CFVR, ρ=0.50; P<0.001). iFR also agreed more closely with CFVR in stenosis classification (iFR area under the receiver operating characteristic curve, 0.82 versus FFR area under the receiver operating characteristic curve, 0.72; P<0.001, for a CFVR of 2). The closer relationship between iFR and CFVR was found for different CFVR cutoffs and was particularly marked in the 0.6 to 0.9 FFR range. Hyperemic FFR flow was similar to baseline iFR flow in functionally significant lesions (FFR ≤0.75; mean FFR flow, 25.8±13.7 cm/s versus mean iFR flow, 21.5±11.7 cm/s; P=0.13). FFR flow was higher than iFR flow in nonsignificant stenoses (FFR >0.75; mean FFR flow, 42.3±22.8 cm/s versus mean iFR flow, 26.1±15.5 cm/s; P<0.001). CONCLUSIONS: When compared with FFR, iFR shows stronger correlation and better agreement with CFVR. These results provide physiological evidence that iFR could potentially be used as a functional index of disease severity, independently from its agreement with FFR.