Assessment of renal sympathetic control using invasive pressure and flow velocity measurements in humans.

Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and is a target for pharmacological and catheter-based therapies. The effect of a physiological sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown. We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, rest, and hyperemia following intrarenal dopamine (30 µg/kg). Changes in perfusion pressure were expressed as the change in mean arterial pressure, and changes in flow were expressed as a percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model. A total of 18 patients (61% male and 39% female) with a median age of 57 yr (range: 27-85 yr) with successful measurements were included. During static handgrip, renal arterial pressure increased by 15.2 mmHg (range: 4.2-53.0 mmHg), whereas flow decreased by 11.2%, but with a large variation between individuals (range: -13.4 to 49.8). Intraglomerular pressure increased by 4.2 mmHg (range: -3.9 to 22.1 mmHg). Flow velocity under resting conditions remained stable, with a median of 100.6% (range: 82.3%-114.6%) compared with baseline. During hyperemia, maximal flow was 180% (range: 111%-281%), whereas intraglomerular pressure decreased by 9.6 mmHg (interquartile range: 4.8 to 13.9 mmHg). Changes in renal pressure and flow during handgrip exercise were significantly correlated (ρ = -0.68, P = 0.002). Measurement of renal arterial pressure and flow velocity during handgrip exercise allows the identification of patients with higher and lower sympathetic control of renal perfusion. This suggests that hemodynamic measurements may be useful to assess the response to therapeutic interventions aimed at altering renal sympathetic control.NEW & NOTEWORTHY Renal sympathetic innervation is important in the homeostasis of systemic and renal hemodynamics. We showed that renal arterial pressure significantly increased and that flow decreased during static handgrip exercise using direct renal arterial pressure and flow measurements in humans, but with a large difference between individuals. These findings may be useful for future studies aimed to assess the effect of interventions that influence renal sympathetic control.

Impact of core laboratory assessment on treatment decisions and clinical outcomes using combined fractional flow reserve and coronary flow reserve measurements - DEFINE-FLOW core laboratory sub-study.

OBJECTIVE: The role of combined FFR/CFR measurements in decision-making on coronary revascularization remains unclear. DEFINE-FLOW prospectively assessed the relationship of FFR/CFR agreement with 2-year major adverse cardiac event (MACE) and target vessel failure (TVF) rates, and uniquely included core-laboratory analysis of all pressure and flow tracings. We aimed to document the impact of core-laboratory analysis on lesion classification, and the relationship between core-laboratory fractional flow reserve (FFR) and coronary flow reserve (CFR) values with clinical outcomes and angina burden during follow-up. METHODS: In 398 vessels (348 patients) considered for intervention, ≥1 coronary pressure/flow tracing was approved by the core-laboratory. Revascularization was performed only when both FFR(≤0.80) and CFR(<2.0) were abnormal, all others were treated medically. RESULTS: MACE was lowest for concordant normal FFR/CFR, but was not significantly different compared with either discordant group (low FFR/normal CFR: HR:1.63; 95%CI:0.61-4.40; P = 0.33; normal FFR/low CFR: HR:1.81; 95%CI:0.66-4.98; P = 0.25). Moreover, MACE did not differ between discordant groups treated medically and the concordant abnormal group undergoing revascularization (normal FFR/low CFR: HR:0.63; 95%CI:0.23-1.73;P = 0.37; normal FFR/low CFR: HR:0.70; 95%CI:0.22-2.21;P = 0.54). Similar findings applied to TVF. CONCLUSIONS: Patients with concordantly normal FFR/CFR have very low 2-year MACE and TVF rates. Throughout follow-up, there were no differences in event rates between patients in whom revascularization was deferred due to preserved CFR despite reduced FFR, and those in whom PCI was performed due to concordantly low FFR and CFR. These findings question the need for routine revascularization in vessels showing low FFR but preserved CFR. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.govNCT02328820.

Principles and pitfalls in coronary vasomotor function testing.

BACKGROUND: Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking. AIMS: In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT. METHODS: For the purposes of this review, we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness. RESULTS: Currently, numerous protocols co-exist and vary in vascular domains tested, the manner in which to test these domains (e.g., preprocedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g., Doppler vs thermodilution technique). CONCLUSIONS: This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ among the few specialised centres that perform CFT as a result of the use of different protocols.

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.

Coronary Flow Capacity to Identify Stenosis Associated With Coronary Flow Improvement After Revascularization: A Combined Analysis From DEFINE FLOW and IDEAL.

Background Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave-free ratio, and CFR. Methods and Results Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect -Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian-Dutch-English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed. CFC classified prerevascularization lesions as normal (14), mildly reduced (40), moderately reduced (31), and severely reduced (48). Lesions with larger impairment of CFC showed greater increase in coronary flow and vice versa (median percent increase in coronary flow by revascularization: 4.2%, 25.9%, 50.1%, and 145.5%, respectively; P<0.001). Compared with the conventional cutoff values of fractional flow reserve, instantaneous wave-free ratio, and CFR, an ischemic CFC defined as moderately to severely reduced CFC showed higher diagnostic accuracy with higher specificity to predict a >50% increase in coronary flow after percutaneous coronary intervention. Receiver operating characteristic curve analysis demonstrated that only CFC has a superior predictive efficacy to CFR (P<0.05). Multivariate analysis revealed lesions with ischemic CFC to be the independent predictor of a significant coronary flow increase after percutaneous coronary intervention (odds ratio, 10.7; 95% CI, 4.6-24.8; P<0.001). Conclusions CFC showed significant improvement of identification of lesions that benefit from revascularization compared with CFR with respect to coronary flow increase. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02328820.

Objective Identification of Intermediate Lesions Inducing Myocardial Ischemia Using Sequential Intracoronary Pressure and Flow Measurements.

Background Although ischemic heart disease has a complex and multilevel origin, the diagnostic approach is mainly focused on focal obstructive disease as assessed by pressure-derived indexes. The prognostic relevance of coronary flow over coronary pressure has been suggested and implies that identification of relevant perfusion abnormalities by invasive physiology techniques is critical for the correct identification of patients who benefit from coronary revascularization. The purpose of this study was to evaluate the diagnostic potential of a sequential approach using pressure-derived indexes instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and coronary flow reserve (CFR) measurements to determine the number of intermediate lesions associated with flow abnormalities after initial pressure measurements. Methods and Results A total of 366 intermediate lesions were assessed with simultaneous intracoronary pressure and flow velocity measurements. Contemporary clinical iFR, FFR, and CFR cut points for myocardial ischemia were applied. A total of 118 (32%) lesions were FFR+ and 136 (37%) lesions were iFR+. Subsequent CFR assessment resulted for FFR in a total of 91 (25%) FFR+/CFR+ and for iFR a total of 111 (30%) iFR+/CFR+ lesions. An iFR, FFR, and invasive flow velocity assessment approach would have yielded 20% of lesions (74 of 366) as ischemic. Conclusions Ultimately, 20% of intermediate lesions are associated with flow abnormalities after applying a pressure and flow velocity sequential approach. If iFR is borderline, FFR has limited additional value, in contrast with CFR. These results emphasize the use of coronary physiology in assessing stenosis severity but may also further question the contemporary reputation of a pressure-based approach as a gold standard for the detection of myocardial ischemia in ischemic heart disease.

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.

Distal Evaluation of Functional performance with Intravascular sensors to assess the Narrowing Effect-combined pressure and Doppler FLOW velocity measurements (DEFINE-FLOW) trial: Rationale and trial design.

BACKGROUND: It remains uncertain if invasive coronary physiology beyond fractional flow reserve (FFR) can refine lesion selection for revascularization or provide additional prognostic value. Coronary flow reserve (CFR) equals the ratio of hyperemic to baseline flow velocity and has a wealth of invasive and noninvasive data supporting its validity. Because of fundamental physiologic relationships, binary classification of FFR and CFR disagrees in approximately 30%-40% of cases. Optimal management of these discordant cases requires further study. AIM: The aim of the study was to determine the prognostic value of combined FFR and CFR measurements to predict the 24-month rate of major adverse cardiac events. Secondary end points include repeatability of FFR and CFR, angina burden, and the percentage of successful FFR/CFR measurements which will not be excluded by the core laboratory. METHODS: This prospective, nonblinded, nonrandomized, and multicenter study enrolled 455 subjects from 12 sites in Europe and Japan. Patients underwent physiologic lesion assessment using the 0.014" Philips Volcano ComboWire XT that provides simultaneous pressure and Doppler velocity sensors. Intermediate coronary lesions received only medical treatment unless both FFR (≤0.8) and CFR (<2.0) were below thresholds. The primary outcome is a 24-month composite of death from any cause, myocardial infarction, and revascularization. CONCLUSION: The DEFINE-FLOW study will determine the prognostic value of invasive CFR assessment when measured simultaneously with FFR, with a special emphasis on discordant classifications. Our hypothesis is that lesions with an intact CFR ≥ 2.0 but reduced FFR ≤ 0.8 will have a 2-year outcome with medical treatment similar to lesions with FFR> 0.80 and CFR ≥ 2.0. Enrollment has been completed, and final follow-up will occur in November 2019.

Long-Term Effects of Transcatheter Aortic Valve Implantation on Coronary Hemodynamics in Patients With Concomitant Coronary Artery Disease and Severe Aortic Stenosis.

Background As younger patients are being considered for transcatheter aortic valve implantation (TAVI), the assessment and treatment of concomitant coronary artery disease is taking on increased importance. Methods and Results Thirteen contemporary lower-risk patients with TAVI with severe aortic stenosis (AS) and moderate-severe coronary lesions were included. Patients underwent assessment of coronary hemodynamics in the presence of severe AS (pre-TAVI), in the absence of severe AS (immediately post-TAVI), and at longer-term follow-up (6 months post-TAVI). Fractional flow reserve decreased from 0.85 (0.76-0.88) pre-TAVI to 0.79 (0.74-0.83) post-TAVI, and then to 0.71 (0.65-0.77) at 6-month follow-up (P<0.001 for all comparisons). Conversely, instantaneous wave-free ratio was not significantly different: 0.82 (0.80-0.90) pre-TAVI, 0.83 (0.77-0.88) post-TAVI, and 0.83 (0.73-0.89) at 6 months (P=0.735). These changes are explained by the underlying coronary flow. Hyperemic whole-cycle coronary flow (fractional flow reserve flow) increased from 26.36 cm/s (23.82-31.82 cm/s) pre-TAVI to 30.78 cm/s (29.70-34.68 cm/s) post-TAVI (P=0.012), to 40.20 cm/s (32.14-50.00 cm/s) at 6-month follow-up (P<0.001 for both comparisons). Resting flow during the wave-free period of diastole was not significantly different: 25.48 cm/s (21.12-33.65 cm/s) pre-TAVI, 24.54 cm/s (20.74-27.88 cm/s) post-TAVI, and 25.89 cm/s (22.57-28.96 cm/s) at 6 months (P=0.500). Conclusions TAVI acutely improves whole-cycle hyperemic coronary flow, with ongoing sustained improvements at longer-term follow-up. This enhanced response to hyperemic stimuli appears to make fractional flow reserve assessment less suitable for patients with severe AS. Conversely, resting diastolic flow is not significantly influenced by the presence of severe AS. Resting indices of coronary stenosis severity, therefore, appear to be more appropriate for this patient population, although large-scale prospective randomized trials will be required to determine the role of coronary physiology in patients with severe AS.

Contribution of Age-Related Microvascular Dysfunction to Abnormal Coronary: Hemodynamics in Patients With Ischemic Heart Disease.

OBJECTIVES: This study sought to investigate the contribution of age-related microcirculatory dysfunction to abnormal coronary hemodynamics in patients with coronary atherosclerosis. BACKGROUND: Impairment in myocardial blood supply in patients with coronary atherosclerosis can be accentuated due to age-related changes in microcirculatory function. METHODS: Intracoronary pressure and flow were measured with the Doppler technique in 299 vessels (228 patients), and the thermodilution technique in 120 vessels (99 patients). In 172 patients, Doppler measurements were also performed in unobstructed vessels. Associations of coronary hemodynamics with aging were studied in both the stenosed and unobstructed arteries. RESULTS: Aging was associated with a progressive increase in minimal microvascular resistance and a progressive decrease in hyperemic flow in both obstructed and nonobstructed coronary arteries. As such, coronary flow reserve decreased with advancing age. Epicardial stenosis severity assessed by resting Pd/Pa, basal stenosis resistance index, and hyperemic stenosis resistance index was equivalent across age groups. By contrast, fractional flow reserve increased with advancing age. Consequently, the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of concomitant focal epicardial and diffuse or microvascular disease (relative risk: 1.6; 95% confidence interval: 1.1 to 2.3; p = 0.017) increased with advancing age, whilst the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of non-flow-limiting stenosis with a healthy microcirculation decreased (relative risk: 0.7; 95% CI: 0.5 to 1.0; p = 0.022). CONCLUSIONS: Aging is associated with progressive pan-myocardial impairment of coronary vasodilatory capacity due to an increase in minimal microvascular resistance. Concomitant aging-related impairment in microvascular function impacts the pathophysiology of ischemic heart disease in the individual patient and is not adequately identified by hyperemic coronary pressure measurements alone.

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.

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

BACKGROUND: Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. METHODS: We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. RESULTS: We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. CONCLUSIONS: The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.

Quantification of Myocardial Mass Subtended by a Coronary Stenosis Using Intracoronary Physiology.

BACKGROUND: In patients with stable coronary artery disease, the amount of myocardium subtended by coronary stenoses constitutes a major determinant of prognosis, as well as of the benefit of coronary revascularization. We devised a novel method to estimate partial myocardial mass (PMM; ie, the amount of myocardium subtended by a stenosis) during physiological stenosis interrogation. Subsequently, we validated the index against equivalent PMM values derived from applying the Voronoi algorithm on coronary computed tomography angiography. METHODS: Based on the myocardial metabolic demand and blood supply, PMM was calculated as follows: PMM (g)=APV×D2×π/(1.24×10-3×HR×sBP+1.6), where APV indicates average peak blood flow velocity; D, vessel diameter; HR, heart rate; and sBP, systolic blood pressure. We calculated PMM to 43 coronary vessels (32 patients) interrogated with pressure and Doppler guidewires, and compared it with computed tomography-based PMM. RESULTS: Median PMM was 15.8 g (Q1, Q3: 11.7, 28.4 g) for physiology-based PMM, and 17.0 g (Q1, Q3: 12.5, 25.9 g) for computed tomography-based PMM (P=0.84). Spearman rank correlation coefficient was 0.916 (P<0.001), and Passing-Bablok analysis revealed absence of both constant and proportional differences (coefficient A: -0.9; 95% CI, -4.5 to 0.9; and coefficient B, 1.00; 95% CI, 0.91 to 1.25]. Bland-Altman analysis documented a mean bias of 0.5 g (limit of agreement: -9.1 to 10.2 g). CONCLUSIONS: Physiology-based calculation of PMM in the catheterization laboratory is feasible and can be accurately performed as part of functional stenosis assessment.

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.

Assessing the Haemodynamic Impact of Coronary Artery Stenoses: Intracoronary Flow Versus Pressure Measurements.

Fractional flow reserve (FFR)-guided percutaneous coronary intervention results in better long-term clinical outcomes compared with coronary angiography alone in intermediate stenoses in stable coronary artery disease (CAD). Coronary physiology measurements have emerged for clinical decision making in interventional cardiology, but the focus lies mainly on epicardial vessels rather than the impact of these stenoses on the myocardial microcirculation. The latter can be quantified by measuring the coronary flow reserve (CFR), a combined pressure and flow index with a strong ability to predict clinical outcomes in CAD. However, combined pressure-flow measurements show 30-40 % discordance despite similar diagnostic accuracy between FFR and CFR, which is explained by the effect of microvascular resistance on both indices. Both epicardial and microcirculatory involvement has been acknowledged in ischaemic heart disease, but clinical implementation remains difficult as it requires individual proficiency. The recent introduced pressure-only index instantaneous wave-free ratio, a resting adenosine-free stenosis assessment, led to a revival of interest in coronary physiology measurements. This review focuses on elaborating the coronary physiological parameters and potential of combined pressure-flow measurements in daily clinical practice.

Fractional Flow Reserve or Coronary Flow Reserve for the Assessment of Myocardial Perfusion : Implications of FFR as an Imperfect Reference Standard for Myocardial Ischemia.

PURPOSE OF REVIEW: Accumulating evidence exists for the value of coronary physiology for clinical decision-making in ischemic heart disease (IHD). The most frequently used pressure-derived index to assess stenosis severity, the fractional flow reserve (FFR), has long been considered the gold standard for this purpose, despite the fact that the FFR assesses solely epicardial stenosis severity and aims to estimate coronary flow impairment in the coronary circulation. The coronary flow reserve (CFR) directly assesses coronary blood flow in the coronary circulation, including both the epicardial coronary artery and the coronary microvasculature, but is nowadays less established than FFR. It is now recognized that both tools may provide insight into the pathophysiological substrate of ischemic heart disease, and that particularly combined FFR and CFR measurements provide a comprehensive insight into the multilevel involvement of IHD. This review discusses the diagnostic and prognostic characteristics, as well as future implications of combined assessment of FFR and CFR pressure and flow measurements as parameters for inducible ischemia. RECENT FINDINGS: FFR and CFR disagree in up to 40% of all cases, giving rise to fundamental questions regarding the role of FFR in contemporary ischemic heart disease management, and implying a renewed approach in clinical management of these patients using combined coronary pressure and flow measurement to allow appropriate identification of patients at risk for cardiovascular events. This review emphasizes the value of comprehensive coronary physiology measurements in assessing the pathophysiological substrate of IHD, and the importance of acknowledging the broad spectrum of epicardial and microcirculatory involvement in IHD. Increasing interest and large clinical trials are expected to further strengthen the potential of advanced coronary physiology in interventional cardiology, consequently inducing reconsideration of current clinical guidelines.