Impact of clinical and haemodynamic factors on coronary flow reserve and invasive coronary flow capacity in non-obstructed coronary arteries: a patient-level pooled analysis of the DEBATE and ILIAS studies.

AIMS: Coronary flow reserve (CFR) is a physiological index for the assessment of myocardial flow impairment due to focal or microcirculatory coronary artery disease (CAD). Coronary flow capacity (CFC) is another flow-based concept in diagnosing ischaemic heart disease, based on hyperaemic average peak velocity (hAPV) and CFR. We evaluated clinical and haemodynamic factors which potentially influence CFR and CFC in non-obstructed coronary arteries. METHODS AND RESULTS: Intracoronary Doppler flow velocity measurements to obtain CFR and CFC were performed after inducing hyperaemia in 390 non-obstructed vessels of patients who were scheduled for elective percutaneous coronary intervention (PCI) of another vessel. Akaike's information criterion (AIC) revealed age, female gender, history of myocardial infarction, hypercholesterolaemia, diastolic blood pressure, oral nitrates and rate pressure product as independent predictors of CFR and CFC. After regression analysis, age and female gender were associated with lower CFR and age was associated with worse CFC in angiographically non-obstructed vessels. CONCLUSIONS: Age and female gender are associated with lower CFR, and age with worse CFC in an angiographically non-obstructed coronary artery. CFC seems to be less sensitive to variations in clinical and haemodynamic parameters than CFR and is therefore a promising tool in contemporary clinical decision making in the cardiac catheterisation laboratory.

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.

Estimation of Intraglomerular Pressure Using Invasive Renal Arterial Pressure and Flow Velocity Measurements in Humans.

BACKGROUND: Glomerular hyperfiltration resulting from an elevated intraglomerular pressure (Pglom) is an important cause of CKD, but there is no feasible method to directly assess Pglom in humans. We developed a model to estimate Pglom in patients from combined renal arterial pressure and flow measurements. METHODS: We performed hemodynamic measurements in 34 patients undergoing renal or cardiac angiography under baseline conditions and during hyperemia induced by intrarenal dopamine infusion (30 µg/kg). For each participant during baseline and hyperemia, we fitted an adapted three-element Windkessel model that consisted of characteristic impedance, compliance, afferent resistance, and Pglom. RESULTS: We successfully analyzed data from 28 (82%) patients. Median age was 58 years (IQR, 52-65), median eGFR was 95 ml/min per 1.73 m2 (IQR, 74-100) using the CKD-EPI formula, 30% had microalbuminuria, and 32% had diabetes. The model showed a mean Pglom of 48.0 mm Hg (SD=10.1) at baseline. Under hyperemia, flow increased by 88% (95% CI, 68% to 111%). This resulted in a 165% (95% CI, 79% to 294%) increase in afferent compliance and a 13.1-mm Hg (95% CI, 10.0 to 16.3) decrease in Pglom. In multiple linear regression analysis, diabetes (coefficient, 10.1; 95% CI, 5.1 to 15.1), BMI (0.99 per kg/m2; 95% CI, 0.38 to 1.59), and renal perfusion pressure (0.42 per mm Hg; 95% CI, 0.25 to 0.59) were significantly positively associated with baseline Pglom. CONCLUSIONS: We constructed a model on the basis of proximal renal arterial pressure and flow velocity measurements that provides an overall estimate of glomerular pressure and afferent and efferent resistance in humans. The model provides a novel research technique to evaluate the hemodynamics of CKD on the basis of direct pressure and flow measurements. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Functional HEmodynamics in patients with and without Renal Artery stenosis (HERA), NL40795.018.12 at the Dutch national trial registry (toetsingonline.nl).

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.

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.

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.

Determining the Predominant Lesion in Patients With Severe Aortic Stenosis and Coronary Stenoses: A Multicenter Study Using Intracoronary Pressure and Flow.

BACKGROUND: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation. METHODS: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2). RESULTS: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s-1 versus post-TAVI 3.04±1.6 mm Hg·cm·s-1 [P=0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [P=0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74. CONCLUSIONS: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.

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.

Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease: Primary Results of the International Multicenter iFR GRADIENT Registry.

OBJECTIVES: The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings. BACKGROUND: In tandem and diffuse disease, offline analysis of continuous iFR pullback measurement has previously been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the online analysis approach (iFR pullback) remains untested. METHODS: Angiographically intermediate tandem and/or diffuse lesions were entered into the international, multicenter iFR GRADIENT (Single instantaneous wave-Free Ratio Pullback Pre-Angioplasty Predicts Hemodynamic Outcome Without Wedge Pressure in Human Coronary Artery Disease) registry. Operators were asked to submit their procedural strategy after angiography alone and then after iFR-pullback measurement incorporating virtual PCI and post-PCI iFR prediction. PCI was performed according to standard clinical practice. Following PCI, repeat iFR assessment was performed and the actual versus predicted post-PCI iFR values compared. RESULTS: Mean age was 67 ± 12 years (81% male). Paired pre- and post-PCI iFR were measured in 128 patients (134 vessels). The predicted post-PCI iFR calculated online was 0.93 ± 0.05; observed actual iFR was 0.92 ± 0.06. iFR pullback predicted the post-PCI iFR outcome with 1.4 ± 0.5% error. In comparison to angiography-based decision making, after iFR pullback, decision making was changed in 52 (31%) of vessels; with a reduction in lesion number (-0.18 ± 0.05 lesion/vessel; p = 0.0001) and length (-4.4 ± 1.0 mm/vessel; p < 0.0001). CONCLUSIONS: In tandem and diffuse coronary disease, iFR pullback predicted the physiological outcome of PCI with a high degree of accuracy. Compared with angiography alone, availability of iFR pullback altered revascularization procedural planning in nearly one-third of patients.

Monocytic microRNA profile associated with coronary collateral artery function in chronic total occlusion patients.

An expansive collateral artery network is correlated with improved survival in case of adverse cardiac episodes. We aimed to identify cellular microRNAs (miRNA; miR) important for collateral artery growth. Chronic total occlusion (CTO) patients (n = 26) were dichotomized using pressure-derived collateral flow index (CFIp) measurements; high collateral capacity (CFIp > 0.39; n = 14) and low collateral (CFIp < 0.39; n = 12) capacity. MiRNA profiling via next generation sequencing from various monocyte phenotypes (freshly isolated monocytes, monocytes cultured without stimulant, or stimulation with lipopolysaccharide, interleukin 4, transforming growth factor beta-1, or interferon gamma) revealed significantly different miRNA expression patterns between high versus low collateral capacity patients. Validation by real-time polymerase chain reaction demonstrated significantly decreased expression of miR339-5p in all stimulated monocyte phenotypes of low collateral capacity patients. MiR339-5p showed significant correlation with CFIp values in stimulated monocytes. Ingenuity pathway analysis of predicted gene targets of miR339-5p and differential gene expression data from high versus low CFIp patients (n = 20), revealed significant association with STAT3 pathway, and also suggested a possible regulatory role for this signaling pathway. These results identify a novel association between miR339-5p and coronary collateral function. Future work examining modulation of miR339-5p and downstream effects on the STAT3 pathway and subsequent collateral vessel growth are warranted.

The IMPACT Study (Influence of Sensor-Equipped Microcatheters on Coronary Hemodynamics and the Accuracy of Physiological Indices of Functional Stenosis Severity).

BACKGROUND: The Navvus pressure sensor-equipped microcatheter allows to measure functional stenosis severity over a work-horse guidewire and is used as a more feasible alternative to regular sensor-equipped wires. However, Navvus is larger in diameter than contemporary sensor-equipped guidewires and may, thereby, influence functional measurements. The present study evaluates the hemodynamic influence of the Navvus microcatheter. METHODS AND RESULTS: In patients with intermediate coronary stenosis, coronary pressure and flow velocity were measured using a dual sensor-equipped guidewire before and after introduction of Navvus. Patients were randomized to microcatheter-first or guidewire-first measurement. The primary end point was the difference in hyperemic stenosis resistance index between measurements before and after introduction of Navvus. Measurements were completed in 28 patients (28 stenoses). Mean hyperemic stenosis resistance was 0.37±0.19 Hg/cm/s for wire-only assessment and 0.48±0.26 Hg/cm/s after Navvus introduction (P<0.001). Bland-Altman analysis documented a mean bias of +0.11 Hg/cm/s (limits of agreement: -0.13 to 0.36), proportional to mean hyperemic stenosis resistance (Spearman ρ =0.61; P=0.001). Passing-Bablok analysis revealed absence of a constant difference but significant proportional difference between the methods. Mean fractional flow reserve was 0.86±0.06 for wire-only assessment and 0.82±0.07 after Navvus introduction (P<0.001). Bland-Altman analysis documented a mean bias of -0.033 (limits of agreement: -0.09 to 0.03), proportional to mean fractional flow reserve (Spearman ρ =0.40; P=0.036). Passing-Bablok analysis revealed significant constant and proportional differences between methods. Similar results were documented for resting indices of stenosis severity. CONCLUSIONS: Introduction of the Navvus microcatheter leads to clinically relevant stenosis severity overestimation in intermediate stenosis.

Vectorcardiographic QRS area identifies delayed left ventricular lateral wall activation determined by electroanatomic mapping in candidates for cardiac resynchronization therapy.

BACKGROUND: Delayed left ventricular (LV) lateral wall (LVLW) activation is considered the electrical substrate underlying LV dysfunction amenable to cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to assess LVLW activation in CRT candidates using coronary venous electroanatomic mapping (EAM) and to investigate whether the QRS area (QRSAREA) on the vectorcardiogram (VCG) can identify delayed LVLW activation. METHODS: Fifty-one consecutive CRT candidates (29 left bundle branch block [LBBB], 15 intraventricular conduction delay [IVCD], 7 right bundle branch block [RBBB]) underwent intraprocedural coronary venous EAM using EnSite NavX. VCGs were constructed from preprocedural digital 12-lead ECGs using the Kors method. QRSAREA was assessed and compared to QRS duration and 5 different LBBB definitions. RESULTS: Delayed LVLW activation (activation time >75% of QRS duration) occurred in 38 of 51 patients (29/29 LBBB, 8/15 IVCD, 1/7 RBBB). QRSAREA was larger in patients with than in patients without delayed LVLW activation (108 ± 42 µVs vs 51 ± 27 µVs, P < .001), and identified delayed LVLW activation better than QRS duration (area under the curve 0.89 [95% confidence interval 0.79-0.99] vs 0.49 [95% confidence interval 0.33-0.65]). QRSAREA >69 µVs diagnosed delayed LVLW activation with a higher sum of sensitivity (87%) and specificity (92%) than any of the LBBB definitions. Of the different LBBB definitions, the European Society of Cardiology textbook definition performed best with sensitivity of 76% and specificity of 100%. CONCLUSION: Coronary venous EAM can be used during CRT implantation to determine the presence of delayed LVLW activation. QRSAREA is a noninvasive alternative for intracardiac measurements of electrical activation, which identifies delayed LVLW activation better than QRS duration and LBBB morphology.