Measurement Of Coronary Flow Reserve Research Articles

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

BackgroundCoronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. Methods and ResultsWe assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. ConclusionsIn this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

Coronary Flow Reserve in Patients With Prior Spontaneous Coronary Artery Dissection and Recurrent Angina.

BackgroundA significant proportion of patients with spontaneous coronary artery dissection (SCAD) have ongoing chronic chest pain despite healing of their dissection. We sought to determine whether coronary microvascular dysfunction contributes to post‐SCAD chronic chest pain by performing coronary reactivity testing in the cardiac catheterization laboratory.Methods and ResultsEighteen patients consented to coronary reactivity testing at least 3 months post‐SCAD. Coronary flow reserve (CFR) and index of microcirculatory resistance were measured in the previously affected SCAD artery and 1 non‐SCAD artery. CFR <2.5 was defined as diagnostic of coronary microvascular dysfunction. An abnormal index of microcirculatory resistance was defined as >25 units. Seventeen women underwent coronary reactivity testing (1 had chronic dissection and was excluded). All presented with myocardial infarction and 2 underwent coronary stenting during the initial SCAD event. Fibromuscular dysplasia was present in 70.6% upon screening renal, iliac, and cerebrovascular arteries. Twelve patients (70.6%) had CFR <2.5 and 13 (76.5%) had an index of microcirculatory resistance >25 in at least 1 artery. There was no difference in the frequency of a low CFR measurement between SCAD and non‐SCAD arteries.ConclusionsAmong patients with chronic chest pain after an SCAD event, >70% had coronary microvascular dysfunction as indicated by abnormal CFR or index of microcirculatory resistance in at least 1 coronary artery on invasive coronary reactivity testing. Presence of coronary microvascular dysfunction in both SCAD and non‐SCAD arteries suggests that underlying microvascular abnormalities from vasculopathies such as coronary fibromuscular dysplasia may be the underlying etiology.

Absolute microvascular resistance by continuous thermodilution predicts microvascular dysfunction after ST-elevation myocardial infarction

AimsContinuous thermodilution using intracoronary saline infusion is a novel technique able to provide accurate measurements of absolute coronary blood flow and microvascular resistance (Rmicro). The aim of this study was to assess the ability of Rmicro, measured by continuous thermodilution, to predict microvascular dysfunction in patients with ST-elevation myocardial infarction. Methods and resultsIn this prospective observational study, continuous thermodilution was used to measure Rmicro in the culprit coronary artery of 32 patients with STEMI (mean age ± SD, 66 ± 10 years; 78% male) immediately post-primary percutaneous coronary intervention (PCI). Concomitant measurements of the index of microvascular resistance (IMR) and coronary flow reserve (CFR) were obtained by bolus thermodilution. Microvascular dysfunction was defined as an IMR > 40 or a CFR < 2. Rmicro was higher in patients with microvascular dysfunction based on the predefined thresholds; for IMR: 863 (IQR, 521–1079) vs 474 (IQR, 337–616) Wood units, p = .004 and for CFR: 633 (IQR, 455–1039) vs 474 (IQR, 271–579) Wood units, p = .02. Receiver-operator characteristic analysis demonstrated that Rmicro was predictive of microvascular dysfunction; area under curve (AUC) 0.800 (95% CI: 0.637–0.963, p = .005) for IMR-defined microvascular dysfunction and AUC 0.758 (95% CI: 0.593–0.924, p = .02) for CFR-defined microvascular dysfunction. An Rmicro threshold of greater than 552 Wood units was optimal for predicting microvascular dysfunction defined by IMR > 40. ConclusionsRmicro is able to identify STEMI patients in whom IMR and CFR measurements suggest significant microvascular dysfunction at the end of primary PCI.

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

BackgroundAlthough 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 ResultsA 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.ConclusionsUltimately, 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.

A randomized trial comparing the acute coronary, systemic, and environmental effects of electronic vaping cigarettes versus heat-not-burn cigarettes in smokers of combustible cigarettes undergoing invasive coronary assessment: rationale and design of the SUR-VAPES 3 trial.

Traditional combustible cigarette (TCC) smoking remains a major cause of preventable cardiovascular morbidity and mortality. Modified risk products (MRP) such as electronic vaping cigarettes (EVC) and heat-not-burn cigarettes (HNBC) may be safer than TCC but may still have detrimental oxidative, platelet and vascular effects of particular importance to people with symptomatic coronary artery disease (CAD). We aimed to compare the acute coronary, systemic and environmental effects of two leading MRP in 20 TCC smokers admitted for invasive coronary assessment of CAD and willing to quit or after prior failed quitting attempts. After confirmation at angiography of an intermediate coronary stenosis, coronary flow reserve (CFR) will be appraised. Patients will then be randomized 1:1 to use a single EVC or a single HNBC in the catheterization laboratory, followed by repeat CFR measurement. The primary endpoint will be the change in CFR before and after product use. Quantitative coronary angiography, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) will also be measured. We expected to accrue results able to: 1) test whether MRP have in general a detrimental impact on coronary vascular function in TCC smokers; 2) test whether EVC have a different impact than HNBC on coronary function; 3) provide ancillary pathophysiologic and translational insights on the acute risk and safety profile of MRP in TCC smokers with established cardiovascular disease, including complex correlations between coronary, cardiac, systemic and environmental effects. In addition, by directly informing participants of their individual results, they will be further empowered to quit TCC. The Sapienza University of Rome-Vascular Assessment of Proatherosclerotic Effects of Smoking (SUR-VAPES) 3 trial will provide important insights into the pathophysiologic cardiovascular impact of EVC and HNBC, also suitable to inform patients and individualize their smoking cessation strategy.

Cardiac impact of arteriovenous fistulas: what tools to assess?

The relationship between arteriovenous access flow (Qa) and cardiovascular changes is complex. Several studies have shown cardiac remodeling and symptoms of heart failure for high-flow arteriovenous fistulas (AVF). To evaluate the early cardiovascular impact of AVF. Forty-seven patients with an AVF, hospitalized for the evaluation of high-flow AVF or a pre-kidney transplant assessment were included. We collected clinical and biological data. We also collected data of the assessment by transthoracic echocardiography, functional evaluation by 6-min-walk test and peak oxygen consumption, and measurement of coronary flow reserve by dynamic myocardial perfusion imaging. The measurement of Qa was performed by color Doppler ultrasound and then indexed to the body surface area (Qai) and to the cardiac output (CO) (Qa/CO). Patients were poorly symptomatic (18 and 1 patients NYHA stage 2 and 3, respectively). There was no correlation between Qa, Qai, or Qa/CO and functional status, assessed by peak oxygen consumption (P = 0.891; P = 0.803; P = 0.939, respectively). Symptomatic patients did not have higher Qa, Qai or Qa/CO than asymptomatic (2260 vs 2197mL/min, P = 0.402; 1257 vs 1256mL/min/m2, P = 0.835; and 34% vs 37%, P = 0.701, respectively). There was no correlation between Qa, Qai or Qa/CO and left ventricular end-diastolic volume or left ventricular ejection fraction. There was no correlation between coronary flow reserve and these 3 parameters of vascular access flow. However, the global longitudinal strain (GLS) was correlated with Qa and Qa/CO (R = 0.331, P = 0.023 and R = 0.380, P = 0.008, respectively). Increase of Qa or Qa/CO was associated with an alteration of the GLS. A cut-off value of 2250mL/min for Qa allowed 83% sensitivity and 63% specificity for detecting an alteration of the GLS > - 18%. A cut-off value of 33% for Qa/CO allowed 92% sensitivity and 65% specificity. Impact of AVF on cardiac parameters is weak. However, GLS is the first parameter to be impacted by the flow of the fistula. Systematic transthoracic echocardiography evaluation with measurement of GLS should be proposed for all patients with Qa > 2250mL/min or Qa/CO > 33%, to detect those at higher risk of cardiac impact of the AVF.

Myocardial Perfusion Imaging Using Positron Emission Tomography.

Coronary artery disease (CAD), also known as ischemic heart disease, is a major cause of morbidity and mortality worldwide, and timely noninvasive diagnosis of clinical and subclinical CAD is imperative to mitigate its burden on individual patients and populations. Positron emission tomography (PET) is a versatile tool that can perform relative myocardial perfusion imaging (MPI) with high accuracy; furthermore, it provides valuable information about the coronary microvasculature using rest and stress myocardial blood flow (MBF) and coronary flow reserve (CFR) measurements. Several radiotracers are approved by the US Food and Drug Administration to help with MPI, MBF, and CFR evaluation. A large body of evidence indicates that evaluation of the coronary microcirculation using MBF and CFR provides strong diagnostic and prognostic data in a multitude of patient populations. This review describes the technical aspects of PET compared to other modalities and discusses its clinical uses for diagnosis and prognosis of coronary arterial epicardial and microcirculatory disease.

Impaired coronary microcirculation is associated with left ventricular diastolic dysfunction in end-stage chronic kidney disease patients.

Coronary vascular dysfunction, as assessed by coronary flow reserve (CFR) in the left anterior descending coronary artery, is found in various conditions including end-stage chronic kidney disease (CKD). Currently, we investigated the associations of CFR with echocardiographic indices of systolic and diastolic cardiac function and identified independent predictors of CFR in hemodialysis patients. End-stage CKD patients treated with hemodialysis (n=29) without known cardiovascular disease were recruited from a Hemodialysis Unit in Northwestern Greece. A thorough echocardiographic evaluation including CFR measurement following dipyridamole infusion was performed in all participants. Arterial stiffness was assessed by measurement of carotid-femoral pulse wave velocity and aortic augmentation index. The mean age of the patients was 63years, and mean duration of hemodialysis was 2.9years. CFR was 1.60±0.37 while dipyridamole caused a significant increase in E'sep , Slat , E'lat , and Stroke volume (P<.05 for all). Independent predictors of CFR were posterior wall thickness (B -0.408, P=.013) and dipyridamole-induced changes in Tei index (B -0.425, P=.007). A severely decreased CFR<1.5 was observed in 52% of the patients. E/E' ratio (B 10.84, P=.014) was the single independent predictor of severely decreased CFR. In end-stage CKD patients on hemodialysis without known cardiovascular disease, impaired coronary vascular function was prevalent and related to increased left ventricular wall thickness, increased filling pressures, and dipyridamole-induced deteriorated myocardial function independently of the presence of wall-motion abnormalities. Further studies are required to clarify the prognostic role of dipyridamole-induced cardiac changes in hemodialysis patients.

Sex Differences in Long-Term Outcomes in Patients With Deferred Revascularization Following Fractional Flow Reserve Assessment: International Collaboration Registry of Comprehensive Physiologic Evaluation.

BackgroundSex‐specific differences may influence prognosis after deferred revascularization following fractional flow reserve (FFR) measurement. This study sought to investigate the sex differences in long‐term prognosis of patients with deferred revascularization following FFR assessment.Methods and ResultsA total of 879 patients (879 vessels) with deferred revascularization with FFR >0.75 who underwent FFR and coronary flow reserve measurements were enrolled from 3 countries (Korea, Japan, and Spain). Long‐term outcomes were assessed in 649 men and 230 women by the patient‐oriented composite outcome (POCO, a composite of any death, any myocardial infarction, and any revascularization). We applied inverse‐probability weighting based on propensity scores to account for differences at baseline between women and men (age, hyperlipidemia, diabetes mellitus, diameter stenosis, lesion length, multivessel disease, FFR, coronary flow reserve. The median follow‐up duration was 1855 days (745–1855 days). Median FFR values were 0.88 (0.83–0.93) in men and 0.89 (0.85–0.94) in women, respectively. The occurrences of POCO were significantly high in men compared with that in women (10.5% versus 4.2%, P=0.007). Kaplan–Meier analysis revealed that women had a significantly lower risk of POCO (χ2=7.2, P=0.007). Multivariate COX proportional hazards regression analysis revealed that age, male, diabetes mellitus, diameter stenosis, lesion length, and coronary flow reserve were independent predictors of POCO. After applying IPW, the hazard ratio of males for POCO was 2.07 (95% CI, 1.07–4.04, P=0.032).ConclusionsThis large multinational study reveals that long‐term outcome differs between women and men in favor of women after FFR‐guided revascularization deferral.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02186093.

Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study.

The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown. To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD. Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148). University hospital. 1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia. Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L). Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%). Data were generated in a large single-center diagnostic study using central adjudication. In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia. European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.

P1443 Sex differences of coronary physiology can be justified by fractional myocardial mass

Abstract Background Women has lower prevalence of coronary artery disease but has higher mortality from acute myocardial infarction. The gender difference in the anatomical-physiological relationship may elucidate the gender difference in the clinical presentation of coronary artery disease. Purpose We hypothesized that the gender difference in the anatomical-physiological relationship may elucidate the gender difference in the clinical presentation of coronary artery disease. Background Women has lower prevalence of coronary artery disease but has higher mortality from acute myocardial infarction. The gender difference in the anatomical-physiological relationship may elucidate the gender difference in the clinical presentation of coronary artery disease. Methods In this multicenter registry, 482 patients who underwent coronary CT angiography and fractional flow reserve (FFR) measurement were enrolled. Fractional myocardial mass (FMM, a vessel-specific amount of myocardium) and %FMM (fraction of FMM to whole myocardial mass) was measured in major coronary arteries and branches. FFR and quantitative coronary angiography (QCA) were interrogated in the subset of 772 vessels. The severity of physiological or anatomical stenosis was assessed by FFR and diameter stenosis (DS), respectively. Results In the analysis of all major epicardial arteries (N = 3,833), FMM was lower in women compared to men (p &amp;lt; 0.01, all), but %FMM was similar between women and men (p = NS, all). Among physiologically assessed 772 vessels, compared to men (N = 587), vessels of women (N = 185) showed smaller dimension (reference diameter (RD) = 2.90 ± 0.65 vs 3.14 ± 0.69 mm, minimal luminal diameter (MLD) = 1.30±.0.57 vs 1.40 ± 0.57 mm (p &amp;lt; 0.05, all), similar severity of stenosis (DS = 55% vs 55% p = NS), and higher FFR (0.81 ± 0.13 vs 0.78 ± 0.15, p &amp;lt; 0.001). In subgroup analysis according to the tertiary categories of DS, RD, and MLD, vessels of women showed higher FFR and lower FMM. Generalized estimating equations modeling demonstrated that gender, DS, RD, MLD, and location in left anterior descending artery were not (p = NS, all) but FMM/MLD were significant predictors for FFR ≤ 0.80 (p = 0.021). Conclusions Compared to men, coronary arteries of women are smaller and supply smaller amount of myocardium even after adjusting for vessel size, which may explain overall higher FFR value of women. This gender difference in anatomical-physiological relationship may explain the gender difference in the clinical coronary artery disease. Abstract P1443 Figure.

Comparison of fractional myocardial mass, a vessel-specific myocardial mass-at-risk, with coronary angiographic scoring systems for predicting myocardial ischemia

AimsThe burden of coronary artery disease has been assessed by various semi-quantitative angiographic scores, which are frequently different each other. A non-invasive and quantitative modality may substitute angiographic sores for prognostic implication and decision of revascularization strategy. We compared fractional myocardial mass (FMM) with angiographic scores for predicting myocardial ischemia. MethodsIn this multicenter registry, 411 patients who underwent coronary computed tomography angiography (CCTA) were followed by invasive coronary angiography and fractional flow reserve (FFR) measurement. CCTA–derived %FMM with diameter stenosis≥70% (%FMM-70) or ≥50% (%FMM-50) were compared with 9 angiographic scores (APPROACH, Duke Jeopardy, BARI, CASS, SYNTAX, Jenkins, BCIS-1, Leaman, Modified Duke) and were tested regarding their performance for predicting FFR≤0.80. ResultsThe performance of %FMM-70 and %FMM-50 were similar to most angiographic scores (%FMM-70, c-statistics = 0.74; %FMM-50, 0.73; angiographic scores, 0.68–0.77). The frequency of FFR≤0.80 increased consistently according to %FMM-70, %FMM-50, and all angiographic scores (p < 0.001, all). The optimal cutoff of %FMM-50 and %FMM-70 for FFR≤0.80 were ≥36.3% and ≥8.7%, respectively. Using these cutoffs, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of %FMM-50 were 81%, 55%, 3%, 67%, 71%, and of %FMM-70 were 67%, 78%, 82%, 61%, 71%. Conclusion%FMM was comparable to angiographic scores for prediction of functional stenosis defined by FFR≤0.80. The integration of the severity of stenosis and the amount of subtended myocardium may improve the detection of the functional significance of vessel.

P4432Coronary microvascular dysfunction in inflammatory bowel disease: Restored after enterectomy

Abstract Background Inflammatory bowel disease (IBD) is a complex multisystem disease characterized by chronic inflammation, which can lead to coronary microvascular dysfunction (CMD). Purpose We aimed to investigate the presence and the severity of CMD in Crohn's disease (CD) and ulcerative colitis (UC) by assessing coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and to elucidate the influence of enterectomy on CMD. Methods Thirty-seven IBD patients (22 CD patients: 39±12 years, 15 UC patients: 52±17 years), and 30 age- and gender-matched control subjects (46±12 years) who have comparable risk factors for coronary artery disease were enrolled. Smokers were excepted from the present study. For CFR measurement, coronary flow velocity was recorded at rest and during hyperemia in the left anterior descending coronary artery induced by intravenous infusion of adenosine triphosphate (0.14 mg/kg/min), and a CFR ≤2.5 calculated as the ratio of hyperemic to basal peak and mean diastolic velocity defined CMD. CFR measurement was repeated before and within 1 year after enterectomy. Serum or plasma cytokines were also measured before and after enterectomy. Results The median disease duration of CD and UC patients were 12 and 6 years. Although none of control subjects had CMD, 38% in IBD patients (CD: 41%, UC: 33%) had CMD. CFR was similarly and significantly lower in CD and UC patients than Control subjects (CD: 2.92±1.03*, UC: 2.99±0.65*, and Control: 3.84±0.75, *p&lt;0.05 vs. Control). Serum levels of TNF-α, IL-6 and hs-CRP were significantly higher in CD and UC patients than Control subjects. Multiple linear regression analysis showed that the presence of IBD and mean diastolic flow velocity at baseline were independently associated with reduced CFR among all study participants (β=−0.324 and −0.614, p=0.001, respectively). CFR in IBD patients with both CMD and non-CMD significantly improved after enterectomy, and the extent of CFR improvement was greater in patients with CMD than those with non-CMD (Figure). Serum levels of IL-6 and hs-CRP significantly reduced among all IBD patients. Conclusion IBD was associated with CMD, which improved after enterectomy.

P5286Cardiac magnetic resonance for quantification of absolute myocardial blood flow: comparison with [15O]H2O positron emission tomography

Abstract Background Quantification of absolute myocardial perfusion using positron emission tomography (PET) augments diagnostic performance and aids risk stratification in patients with coronary artery disease (CAD). Similar to PET, cardiac magnetic resonance imaging (CMR) allows for quantification of absolute myocardial blood flow (MBF). To date, quantitative CMR perfusion has not been compared with [15O]H2O PET, which is considered to be the gold standard for quantification of MBF. Purpose The purpose of this study was to compare CMR measurements of absolute myocardial perfusion to those obtained using [15O]H2O PET. Methods Fifty-one patients with stable CAD underwent [15O]H2O PET followed by CMR within 7 days. Late gadolinium enhancement was used to rule out presence of scar tissue. CMR perfusion imaging was performed using a single bolus dual sequence technique. Myocardial perfusion was quantified for the three main vascular territories at rest and during vasodilator stress. Results Pooled CMR estimates of absolute MBF correlated well with PET (r=0.79; p&lt;0.001) and showed good agreement (intraclass correlation coefficient [ICC]=0.78; p&lt;0.001). However, rest and stress MBF correlated weakly (r=0.31; p&lt;0.001 for rest MBF and r=0.35; p&lt;0.001 for stress MBF, figure) and showed poor agreement between PET and CMR (ICC=0.24; p&lt;0.001 for rest MBF and ICC=0.34; p&lt;0.001 for stress MBF). Similarly, CMR derived coronary flow reserve (CFR) correlated weakly (r=0.28; p&lt;0.001) and showed poor agreement with PET derived CFR (ICC=0.23; p&lt;0.001). Nevertheless, for a cut-off value of 2.3 mL/min/g for stress MBF and 2.5 for CFR, CMR and PET were concordant in 116 (79%) vascular territories for stress MBF and 104 (75%) vascular territories for CFR. Per vessel – CMR vs PET perfusion Conclusions Resting MBF, stress MBF and CFR measurements correlated poorly with [15O]H2O PET. Nevertheless, stress MBF and CFR were concordant between CMR and [15O]H2O PET in 79% and 75% of vascular territories, respectively. Acknowledgement/Funding None

Physiologic Characteristics and Clinical Outcomes of Patients With Discordance Between FFR and iFR

ObjectivesThis study evaluated the physiologic characteristics of discordant lesions between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) and the prognosis at 5 years. BackgroundFFR or iFR have been standard methods for assessing the functional significance of coronary artery stenosis. However, limited data exist about the physiologic characteristics of discordant lesions and the prognostic implications resulting from these lesions. MethodsA total of 840 vessels from 596 patients were classified according to iFR and FFR; high iFR–high FFR (n = 580), low iFR–high FFR (n = 40), high iFR–low FFR (n = 69), and low iFR–low FFR (n = 128) groups, which were compared with a control group (n = 23). The differences in coronary circulatory indices including the coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and resistance reserve ratio (RRR) (resting distal arterial pressure × mean transit time / hyperemic distal arterial pressure × hyperemic mean transit time), which reflect the vasodilatory capacity of coronary microcirculation, were compared. Patient-oriented composite outcomes (POCO) at 5 years including all-cause death, any myocardial infarction, and any revascularization were compared among patients with deferred lesions. ResultsIn the low iFR–high FFR group, CFR, RRR, and IMR measurements were similar to the low iFR–low FFR group: CFR 2.71 versus 2.43 (p = 0.144), RRR 3.36 versus 3.68 (p = 0.241), and IMR 18.51 versus 17.38 (p = 0.476). In the high iFR–low FFR group, the CFR, RRR, and IMR measurements were similar to the control group: CFR 2.95 versus 3.29 (p = 0.160), RRR 4.28 versus 4.00 (p = 0.414), and IMR 17.44 versus 17.06 (p = 0.818). Among the 4 groups, classified by iFR and FFR, CFR and RRR were all significantly different, except for IMR. However, there were no significant differences in the rates of POCO, regardless of discordance between the iFR and FFR. Only the low iFR–low FFR group had a higher POCO rate compared with the high iFR–high FFR group (adjusted hazard ratio: 2.46; 95% confidence interval: 1.17 to 5.16; p = 0.018). ConclusionsDifferences in coronary circulatory function were found, especially in the vasodilatory capacity between the low iFR–high FFR and high iFR–low FFR groups. FFR–iFR discordance was not related to an increased risk of POCO among patients with deferred lesions at 5 years. (Clinical, Physiological and Prognostic Implication of Microvascular Status;NCT02186093; Physiologic Assessment of Microvascular Function in Heart Transplant Patients; NCT02798731)

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

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. 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. 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. 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.

Clinical characteristics and biomarkers of coronary microvascular dysfunction and obstructive coronary artery disease

ObjectiveThe purpose of this study was to determine the clinical characteristics and biomarkers in patients with coronary microvascular dysfunction (CMVD) and to compare them with patients with obstructive coronary artery disease (OCAD).MethodsWe conducted a single-center, hospital-based, observational, descriptive, comparative, clinical study of 40 patients, including 20 patients with CMVD and 20 with OCAD. We assessed laboratory biomarkers (low-density lipoprotein [LDL], high-density lipoprotein [HDL], red blood cell distribution width [RDW], brain natriuretic protein [BNP], troponin I), and PET/CT coronary flow reserve was performed.ResultsThe mean coronary flow reserve (CFR) in patients with CMVD was 1.96±0.55. Mean low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the CMVD subgroup (2.53±0.63 mmol/L) compared with the OCAD subgroup (1.76±0.97 mmol/L). Logistic regression analysis identified LDL-C as a predictor for the development of CMVD (odds ratio, 5.24).ConclusionIt is difficult to differentiate between OCAD and CMVD based on the patient’s medical history, clinical characteristics, and coronary angiography results. Further investigations may be needed to allow an accurate diagnosis. CFR measurements based on non-invasive positron emission tomography/computed tomography may aid the diagnosis of CMVD. We also identified LDL-C as a predictor for the development of CMVD.

Feasibility, safety and effectiveness in measuring microvascular resistance with regadenoson.

AIMThe study aims to test whether simultaneous measurement of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) is feasible, safe and effective during regadenoson-induced hyperemia.METHODS AND RESULTSFFR, CFR and IMR were measured simultaneously during regadenoson (Rapiscan 400 μg) -induced hyperemia in 50 patients with stable coronary artery disease with a SYNTAX score of <22. Simultaneous measurement of FFR, CFR and IMR was technically feasible in all cases (50/50). No side effects occurred and even patients fulfilling classical contraindications for the use of adenosine (10/50) could be included. Regadenoson-induced hyperemia remained stable after maximal pressure drop for more than 35 sec as measured by systemic aortic and distal coronary pressure. There was a significant drop in transit mean time from baseline to hyperemia of more than 50% (1.0 ± 0.6 s vs. 0.4 ± 0.2 s, p < 0.01). Patients' mean IMR value was 23.4, and IMR values above 75th percentile significantly correlated with metformin demanding diabetes mellitus with OR 21.76 and nicotine abuse with OR 10.28.CONCLUSIONA single intravenous regadenoson bolus via peripheral line increases coronary blood flow without harmful systemic side effects enabling interventionists to simultaneously assess FFR, CFR and IMR in patients with stable coronary artery disease.

Relationship between FFR, CFR and coronary microvascular resistance - Practical implications for FFR-guided percutaneous coronary intervention.

ObjectiveThe aim was threefold: 1) expound the independent physiological parameters that drive FFR, 2) elucidate contradictory conclusions between fractional flow reserve (FFR) and coronary flow reserve (CFR), and 3) highlight the need of both FFR and CFR in clinical decision making. Simple explicit theoretical models were supported by coronary data analyzed retrospectively.MethodologyFFR was expressed as a function of pressure loss coefficient, aortic pressure and hyperemic coronary microvascular resistance. The FFR-CFR relationship was also demonstrated mathematically and was shown to be exclusively dependent upon the coronary microvascular resistances. The equations were validated in a first series of 199 lesions whose pressures and distal velocities were monitored. A second dataset of 75 lesions with pre- and post-PCI measures of FFR and CFR was also analyzed to investigate the clinical impact of our hemodynamic reasoning.ResultsHyperemic coronary microvascular resistance and pressure loss coefficient had comparable impacts (45% and 49%) on FFR. There was a good concordance (y = 0.96 x − 0.02, r2 = 0.97) between measured CFR and CFR predicted by FFR and coronary resistances. In patients with CFR < 2 and CFR/FFR ≥ 2, post-PCI CFR was significantly >2 (p < 0.001), whereas it was not (p = 0.94) in patients with CFR < 2 and CFR/FFR < 2.ConclusionThe FFR behavior and FFR-CFR relationship are predictable from basic hemodynamics. Conflicting conclusions between FFR and CFR are explained from coronary vascular resistances. As confirmed by our results, FFR and CFR are complementary; they could jointly contribute to better PCI guidance through the CFR-to-FFR ratio in patients with coronary artery disease.

Coronary Flow Reserve Assessment of Orbital Atherectomy: An Observational Pilot Study

The aim of this prospective observational pilot study was to observe the impact of orbital atherectomy (OA) on the coronary microcirculation via coronary flow reserve (CFR) measurements. Fifteen subjects who had successful OA and stent placement with no procedural complication were enrolled at 3 hospitals in the U.S. Baseline and hyperemic velocities were 16 ± 5.2 and 36 ± 14 cm/sec, respectively. The average CFR post-procedure was within the normal range at 2.23 ± 0.33. The observation of normal CFR following OA may be attributed to the orbital action of the device that allows for continuous flow during treatment, minimizing a bolus embolization effect which can impact microvascular function.